23 results on '"Streicher, Katie"'
Search Results
2. Efficacy, Safety, and Pharmacokinetics of AZD7442 (Tixagevimab/Cilgavimab) for Prevention of Symptomatic COVID-19: 15-Month Final Analysis of the PROVENT and STORM CHASER Trials
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Levin, Myron J., Ustianowski, Andrew, De Wit, Stephane, Beavon, Rohini, Thissen, Jesse, Seegobin, Seth, Dey, Kanika, Near, Karen A., Streicher, Katie, Kiazand, Alexandre, and Esser, Mark T.
- Abstract
Antibodies are proteins produced by the body’s immune system to specifically target foreign substances, such as viruses. AZD7442 is made up of an antibody pair (tixagevimab and cilgavimab) that specifically bind and neutralize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing coronavirus disease 2019 (COVID-19). AZD7442 was designed to give several months of protection against the virus. These antibodies were tested in two clinical trials to see if they could either protect people from getting COVID-19 (PROVENT trial) or prevent people already exposed to SARS-CoV-2 from getting COVID-19 (STORM CHASER trial). In the two trials, approximately 6000 adults received AZD7442 or placebo (injections that look exactly like AZD7442 but contain no medicine). Protection against COVID-19 was monitored for up to 1 year, and safety for up to 15 months. The percentage of trial participants who reported side effects was similar in the AZD7442 and placebo groups, in both trials. The PROVENT trial showed that AZD7442 reduced the risk of getting COVID-19 up to 6 months and protected against severe COVID-19 for up to 1 year. In STORM CHASER, participants were treated after SARS-CoV-2 exposure but before a positive COVID-19 test. Some participants were already infected with SARS-CoV-2 at the start of the trial, others were not. STORM CHASER showed that AZD7442 protected people against COVID-19 for up to 6 months if they were not already infected at the start. The results of these trials provide proof of concept to support the long-term safety of AZD7442 for the prevention of COVID-19.
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- 2024
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3. Safety, Efficacy and Pharmacokinetics of AZD7442 (Tixagevimab/Cilgavimab) for Treatment of Mild-to-Moderate COVID-19: 15-Month Final Analysis of the TACKLE Trial.
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Hobbs, F. D. Richard, Montgomery, Hugh, Padilla, Francisco, Simón-Campos, Jesus Abraham, Arbetter, Douglas, Seegobin, Seth, Kiazand, Alexandre, Streicher, Katie, Martinez-Alier, Nuria, Cohen, Taylor S., and Esser, Mark T.
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- 2024
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4. Effect of Tezepelumab on the Humoral Immune Response to Seasonal Quadrivalent Influenza Vaccination in Patients with Moderate to Severe Asthma: The Phase 3b VECTOR Study
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Cole, Jeremy, Cąpała-Szczurko, Iwona, Roseti, Stephanie, Chen, Claudia, Caveney, Scott, Aksyuk, Anastasia A., Streicher, Katie, Ponnarambil, Sandhia, and Colice, Gene
- Abstract
Introduction: Annual influenza vaccinations are recommended for adolescents and adults with moderate to severe asthma. This study investigated the effect of tezepelumab, a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin, on the humoral immune response to the quadrivalent seasonal influenza vaccine in patients with moderate to severe asthma. Methods: VECTOR was a phase 3b, randomized, multicenter, double-blind, parallel-group, placebo-controlled study. Adolescents (aged 12–17 years) and young adults (aged 18–21 years) with moderate to severe asthma were enrolled across 15 centers in the USA. Patients received tezepelumab 210 mg or placebo subcutaneously at weeks 0, 4, 8, and 12, and a single dose of inactivated quadrivalent seasonal influenza vaccine at week 12 before receiving study treatment. Immediately before vaccination and at 4 weeks postvaccination (week 16), strain-specific antibody responses were assessed for four influenza antigens by hemagglutination inhibition (HAI) and microneutralization (MN) assays. Safety was assessed. Results: Seventy patients were randomized to tezepelumab (n= 35) or placebo (n= 35). There were no meaningful differences in HAI or MN antibody responses between treatment groups at week 16. HAI assay geometric mean fold rises (GMFRs) for influenza strains were 1.76–7.34 for tezepelumab and 1.46–4.75 for placebo. MN assay GMFRs were 4.00–14.56 for tezepelumab and 3.56–10.62 for placebo. In the HAI assay, a fourfold or larger rise in antibody titer from weeks 12 to 16 occurred in 15.2–78.8% and 15.2–51.5% of tezepelumab and placebo recipients, respectively, and 97.0–100% of patients in both treatment groups achieved an antibody titer of at least 40 at week 16. No unexpected safety findings occurred. Conclusion: There was no observed suppression of the humoral immune response after influenza vaccination in adolescents and young adults with moderate to severe asthma treated with tezepelumab. Therefore, the influenza vaccine can be administered to this patient population during tezepelumab treatment. ClinicalTrials.gov identifier: NCT05062759
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- 2024
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5. Safety, Efficacy and Pharmacokinetics of AZD7442 (Tixagevimab/Cilgavimab) for Treatment of Mild-to-Moderate COVID-19: 15-Month Final Analysis of the TACKLE Trial
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Hobbs, F. D. Richard, Montgomery, Hugh, Padilla, Francisco, Simón-Campos, Jesus Abraham, Arbetter, Douglas, Seegobin, Seth, Kiazand, Alexandre, Streicher, Katie, Martinez-Alier, Nuria, Cohen, Taylor S., and Esser, Mark T.
- Abstract
Introduction: In the phase 3 TACKLE study, outpatient treatment with AZD7442 (tixagevimab/cilgavimab) was well tolerated and significantly reduced progression to severe disease or death through day 29 in adults with mild-to-moderate coronavirus disease 2019 (COVID-19) at the primary analysis. Here, we report data from the final analysis of the TACKLE study, performed after approximately 15 months’ follow-up. Methods: Eligible participants were randomized 1:1 and dosed within 7 days of symptom onset with 600 mg intramuscular AZD7442 (n= 456; 300 mg tixagevimab/300 mg cilgavimab) or placebo (n= 454). Results: Severe COVID-19 or death through day 29 occurred in 4.4% and 8.8% of participants who received AZD7442 or placebo, a relative risk reduction (RRR) of 50.4% [95% confidence interval (CI) 14.4, 71.3; p= 0.0096]; among participants dosed within 5 days of symptom onset, the RRR was 66.9% (95% CI 31.1, 84.1; p= 0.002). Death from any cause or hospitalization for COVID-19 complications or sequelae through day 169 occurred in 5.0% of participants receiving AZD7442 versus 9.7% receiving placebo, an RRR of 49.2% (95% CI 14.7, 69.8; p= 0.009). Adverse events occurred in 55.5% and 55.9% of participants who received AZD7442 or placebo, respectively, and were mostly mild or moderate in severity. Serious adverse events occurred in 10.2% and 14.4% of participants who received AZD7442 or placebo, respectively, and deaths occurred in 1.8% of participants in both groups. Serum concentration–time profiles recorded over 457 days were similar for AZD7442, tixagevimab, and cilgavimab, and were consistent with the extended half-life reported for AZD7442 (approx. 90 days). Conclusions: AZD7442 reduced the risk of progression to severe COVID-19, hospitalization, and death, was well tolerated through 15 months, and exhibited predictable pharmacokinetics in outpatients with mild-to-moderate COVID-19. These data support the long-term safety of using long-acting monoclonal antibodies to treat COVID-19. Trial Registration: Clinicaltrials.gov, NCT04723394. (
https://clinicaltrials.gov/study/NCT04723394 . Graphical Abstract:- Published
- 2024
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6. Analysis of SARS-CoV-2 Emergent Variants Following AZD7442 (Tixagevimab/Cilgavimab) for Early Outpatient Treatment of COVID-19 (TACKLE Trial).
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Kijak, Gustavo H., Ahani, Bahar, Arbetter, Douglas, Chuecos, Fernando, Gopalakrishnan, Vancheswaran, Beloor, Jagadish, Brady, Tyler, Nguyen, Amy, Roe, Tiffany L., Schuko, Nicolette, Zhang, Tianhui, Hobbs, F. D. Richard, Padilla, Francisco, Kelly, Elizabeth J., Montgomery, Hugh, and Streicher, Katie
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- 2023
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7. Analysis of SARS-CoV-2 Emergent Variants Following AZD7442 (Tixagevimab/Cilgavimab) for Early Outpatient Treatment of COVID-19 (TACKLE Trial)
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Kijak, Gustavo H., Ahani, Bahar, Arbetter, Douglas, Chuecos, Fernando, Gopalakrishnan, Vancheswaran, Beloor, Jagadish, Brady, Tyler, Nguyen, Amy, Roe, Tiffany L., Schuko, Nicolette, Zhang, Tianhui, Hobbs, F. D. Richard, Padilla, Francisco, Kelly, Elizabeth J., Montgomery, Hugh, and Streicher, Katie
- Abstract
Introduction: AZD7442 (tixagevimab/cilgavimab) comprises neutralising monoclonal antibodies (mAbs) that bind to distinct non-overlapping epitopes on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. Viral evolution during mAb therapy can select for variants with reduced neutralisation susceptibility. We examined treatment-emergent SARS-CoV-2 variants during TACKLE (NCT04723394), a phase 3 study of AZD7442 for early outpatient treatment of coronavirus disease 2019 (COVID-19). Methods: Non-hospitalised adults with mild-to-moderate COVID-19 were randomised and dosed ≤ 7 days from symptom onset with AZD7442 (n= 452) or placebo (n= 451). Next-generation sequencing of the spike gene was performed on SARS-CoV-2 reverse-transcription polymerase chain reaction-positive nasopharyngeal swabs at baseline and study days 3, 6, and 15 post dosing. SARS-CoV-2 lineages were assigned using spike nucleotide sequences. Amino acid substitutions were analysed at allele fractions (AF; % of sequence reads represented by substitution) ≥ 25% and 3% to 25%. In vitro susceptibility to tixagevimab, cilgavimab, and AZD7442 was evaluated for all identified treatment-emergent variants using a pseudotyped microneutralisation assay. Results: Longitudinal spike sequences were available for 461 participants (AZD7442, n= 235; placebo, n= 226) and showed that treatment-emergent variants at any time were rare, with 5 (2.1%) AZD7442 participants presenting ≥ 1 substitution in tixagevimab/cilgavimab binding sites at AF ≥ 25%. At AF 3% to 25%, treatment-emergent variants were observed in 15 (6.4%) AZD7442 and 12 (5.3%) placebo participants. All treatment-emergent variants showed in vitro susceptibility to AZD7442. Conclusion: These data indicate that AZD7442 creates a high genetic barrier for resistance and is a feasible option for COVID-19 treatment.
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- 2023
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8. Outpatient Treatment with AZD7442 (Tixagevimab/Cilgavimab) Prevented COVID-19 Hospitalizations over 6 Months and Reduced Symptom Progression in the TACKLE Randomized Trial.
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Hobbs, F. D. Richard, Montgomery, Hugh, Padilla, Francisco, Simón-Campos, Jesus Abraham, Kim, Kenneth, Arbetter, Douglas, Padilla, Kelly W., Reddy, Venkatesh Pilla, Seegobin, Seth, Streicher, Katie, Templeton, Alison, Viani, Rolando M., Johnsson, Eva, Koh, Gavin C. K. W., and Esser, Mark T.
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- 2023
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9. Efficacy and safety of intramuscular administration of tixagevimab–cilgavimab for early outpatient treatment of COVID-19 (TACKLE): a phase 3, randomised, double-blind, placebo-controlled trial.
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Montgomery, Hugh, Hobbs, F D Richard, Padilla, Francisco, Arbetter, Douglas, Templeton, Alison, Seegobin, Seth, Kim, Kenneth, Campos, Jesus Abraham Simón, Arends, Rosalinda H, Brodek, Bryan H, Brooks, Dennis, Garbes, Pedro, Jimenez, Julieta, Koh, Gavin C K W, Padilla, Kelly W, Streicher, Katie, Viani, Rolando M, Alagappan, Vijay, Pangalos, Menelas N, and Esser, Mark T
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COVID-19 treatment ,COVID-19 ,INTRAMUSCULAR injections ,ANTIGEN analysis ,COVID-19 vaccines - Abstract
Early intramuscular administration of SARS-CoV-2-neutralising monoclonal antibody combination, tixagevimab–cilgavimab, to non-hospitalised adults with mild to moderate COVID-19 has potential to prevent disease progression. We aimed to evaluate the safety and efficacy of tixagevimab–cilgavimab in preventing progression to severe COVID-19 or death. TACKLE is an ongoing, phase 3, randomised, double-blind, placebo-controlled study conducted at 95 sites in the USA, Latin America, Europe, and Japan. Eligible participants were non-hospitalised adults aged 18 years or older with a laboratory-confirmed SARS-CoV-2 infection (determined by RT-PCR or an antigen test) from any respiratory tract specimen collected 3 days or less before enrolment and who had not received a COVID-19 vaccination. A WHO Clinical Progression Scale score from more than 1 to less than 4 was required for inclusion and participants had to receive the study drug 7 days or less from self-reported onset of mild to moderate COVID-19 symptoms or measured fever. Participants were randomly assigned (1:1) to receive either a single tixagevimab–cilgavimab 600 mg dose (two consecutive 3 mL intramuscular injections, one each of 300 mg tixagevimab and 300 mg cilgavimab) or placebo. Randomisation was stratified (using central blocked randomisation with randomly varying block sizes) by time from symptom onset, and high-risk versus low-risk of progression to severe COVID-19. Participants, investigators, and sponsor staff involved in the treatment or clinical evaluation and monitoring of the participants were masked to treatment-group assignments. The primary endpoints were severe COVID-19 or death from any cause through to day 29, and safety. This study is registered with ClinicalTrials.gov , NCT04723394. Between Jan 28, 2021, and July 22, 2021, 1014 participants were enrolled, of whom 910 were randomly assigned to a treatment group (456 to receive tixagevimab–cilgavimab and 454 to receive placebo). The mean age of participants was 46·1 years (SD 15·2). Severe COVID-19 or death occurred in 18 (4%) of 407 participants in the tixagevimab–cilgavimab group versus 37 (9%) of 415 participants in the placebo group (relative risk reduction 50·5% [95% CI 14·6–71·3]; p=0·0096). The absolute risk reduction was 4·5% (95% CI 1·1–8·0; p<0·0001). Adverse events occurred in 132 (29%) of 452 participants in the tixagevimab–cilgavimab group and 163 (36%) of 451 participants in the placebo group, and were mostly of mild or moderate severity. There were three COVID-19-reported deaths in the tixagevimab–cilgavimab group and six in the placebo group. A single intramuscular tixagevimab–cilgavimab dose provided statistically and clinically significant protection against progression to severe COVID-19 or death versus placebo in unvaccinated individuals and safety was favourable. Treating mild to moderate COVID-19 earlier in the disease course with tixagevimab–cilgavimab might lead to more favourable outcomes. AstraZeneca. [ABSTRACT FROM AUTHOR]
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- 2022
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10. Outpatient Treatment with AZD7442 (Tixagevimab/Cilgavimab) Prevented COVID-19 Hospitalizations over 6 Months and Reduced Symptom Progression in the TACKLE Randomized Trial
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Hobbs, F. D. Richard, Montgomery, Hugh, Padilla, Francisco, Simón-Campos, Jesus Abraham, Kim, Kenneth, Arbetter, Douglas, Padilla, Kelly W., Reddy, Venkatesh Pilla, Seegobin, Seth, Streicher, Katie, Templeton, Alison, Viani, Rolando M., Johnsson, Eva, Koh, Gavin C. K. W., and Esser, Mark T.
- Abstract
Antibodies are proteins produced by the body’s immune system to specifically combat foreign substances, such as viruses. Tixagevimab and cilgavimab are a pair of antibodies that bind to a specific part of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19). When they bind to the virus, they reduce its ability to cause disease. These antibodies were tested in a clinical trial to see if they could prevent people with COVID-19 from being hospitalized or dying. Around 900 adults took part in this clinical trial. These people all had COVID-19 but were not sick enough to be in hospital. Half of this group were treated with a dose of tixagevimab and cilgavimab, given as two injections. The other half received a placebo (injections that look exactly like the tixagevimab and cilgavimab injections but contain no medicine). The study found that, over 6 months, people with COVID-19 who received tixagevimab and cilgavimab were less likely to need to go to hospital than people who received the placebo. They were also less likely to die of COVID-19. Tixagevimab and cilgavimab also helped to improve COVID-19 symptoms. People who received the antibodies saw their symptoms improve faster than people who received the placebo. They were also less likely to have symptoms that got worse. Most people felt better within 1–2 weeks of getting treatment. No safety issues were found with tixagevimab and cilgavimab compared with placebo.
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- 2023
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11. TEZEPELUMAB DID NOT APPEAR TO AFFECT THE HUMORAL IMMUNE RESPONSE TO SEASONAL QUADRIVALENT INFLUENZA VACCINATION IN PATIENTS WITH MODERATE-TO-SEVERE ASTHMA (VECTOR)
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COLE, JEREMY, CAPALA-SZCZURKO, IWONA, ROSETI, STEPHANIE, CHEN, CLAUDIA, CAVENEY, SCOTT, SAWYER, ANGELA, AKSYUK, ANASTASIA, STREICHER, KATIE, and COLICE, GENE
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- 2023
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12. Development and analytical performance of a new ARCHITECT automated dipeptidyl peptidase-4 immunoassay
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Hemken, Philip M., Jeanblanc, Nicolette M., Rae, Tracey, Brophy, Susan E., Datwyler, Maria J., Xu, Ying, Manetz, T. Scott, Vainshtein, Inna, Liang, Meina, Xiao, Xiaodong, Chowdhury, Partha S., Chang, Chien-ying, Streicher, Katie, Greenlees, Lydia, Ranade, Koustubh, and Davis, Gerard J.
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Dipeptidyl peptidase-4 (DPP-4) may be a suitable biomarker to identify people with severe asthma who have greater activation of the interleukin-13 (IL-13) pathway and may therefore benefit from IL-13-targeted treatments. We report the analytical performance of an Investigational Use Only immunoassay and provide data on the biological range of DPP-4 concentrations.
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- 2017
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13. Safety and tolerability of an anti-CD19 monoclonal antibody, MEDI-551, in subjects with systemic sclerosis: a phase I, randomized, placebo-controlled, escalating single-dose study
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Schiopu, Elena, Chatterjee, Soumya, Hsu, Vivien, Flor, Armando, Cimbora, Daniel, Patra, Kaushik, Yao, Wenliang, Li, Jing, Streicher, Katie, McKeever, Kathleen, White, Barbara, Katz, Eliezer, Drappa, Jorn, Sweeny, Sarah, and Herbst, Ronald
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Systemic sclerosis (SSc) is a clinically heterogeneous, life-threatening disease characterized by fibrosis, microvasculopathy, and autoimmunity. Extensive nonclinical and clinical data implicate B cells in the pathogenesis of SSc. MEDI-551 is an investigational humanized monoclonal antibody that targets the B cell surface antigen CD19 and mediates antibody-dependent, cell-mediated cytotoxicity of B cells. This clinical study evaluated the safety and tolerability, pharmacokinetics, and pharmacodynamics of MEDI-551 in subjects with SSc. This phase I multicenter, randomized, double-blind, placebo-controlled, single escalating dose study enrolled adult subjects with either limited or diffuse cutaneous SSc. A single intravenous dose of MEDI-551 was administered, and safety and tolerability were evaluated. MEDI-551 pharmacokinetics (PK), pharmacodynamics, and immunogenicity were also assessed. Safety assessments included the incidence of adverse events and changes in clinical and laboratory results. MEDI-551 serum concentrations, effects on circulating and tissue B cells and plasma cells (PCs), and antidrug antibodies were analyzed. Modified Rodnan skin score (MRSS) and pulmonary function tests were used to explore the clinical effect of MEDI-551. The study enrolled 28 subjects with SSc (mean age, 47.3 years; 67.9 % female). Twenty-four received a single dose of MEDI-551 (0.1–10.0 mg/kg) and four received placebo. Treatment-emergent adverse events (TEAEs) occurred in 95.8 % of subjects in the MEDI-551 group and in 75.0 % of subjects in the placebo group; the majority of TEAEs were mild or moderate in severity. Two serious adverse events were considered possibly related to the study drug. One death, deemed not related to the study drug, occurred in a MEDI-551-treated subject. MEDI-551 exhibited linear PK in the dose range of 1.0 to 10.0 mg/kg, and more rapid clearance at lower doses. Dose-dependent depletion of circulating B cells and plasma cells was observed. MRSS assessments suggest a possible clinical effect of MEDI-551 on affected skin. A single escalating dose of MEDI-551 was tolerable and safe in this subject population. B cell depletion was achieved and was dose dependent. A signal of clinical effect was observed. Based on these results, further investigation of MEDI-551 as a disease-modifying treatment for SSc is warranted. www.clinicaltrials.govidentifier, NCT00946699; registered 23 July 2009.
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- 2016
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14. Efficacy and safety of tralokinumab in patients with severe uncontrolled asthma: a randomised, double-blind, placebo-controlled, phase 2b trial.
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Brightling, Christopher E, Chanez, Pascal, Leigh, Richard, O'Byrne, Paul M, Korn, Stephanie, She, Dewei, May, Richard D, Streicher, Katie, Ranade, Koustubh, and Piper, Edward
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INTERLEUKIN-13 ,ASTHMA ,MONOCLONAL antibodies - Abstract
Summary Background Interleukin 13 is a central mediator of asthma. Tralokinumab is a human interleukin-13 neutralising monoclonal antibody. We aimed to assess the efficacy and safety of two dosing regimens of tralokinumab in patients with severe uncontrolled asthma. Methods We did a randomised, double-blind, placebo-controlled, parallel-group, multicentre, phase 2b study at 98 sites in North America, South America, Europe, and Asia. Patients aged 18–75 years with severe asthma and two to six exacerbations in the previous year were randomly assigned (1:1), via an interactive voice-response or web-response system, to one of two dosing regimen groups (every 2 weeks, or every 2 weeks for 12 weeks then every 4 weeks) and further randomised (2:1), via computer-generated permuted-block randomisation (block size of six), to receive tralokinumab 300 mg or placebo for 1 year. All participants received high-dose fluticasone and salmeterol and continued other pre-study controller drugs. Treatment was administered by an unmasked study investigator not involved in the management of patients; all other study site personnel, patients, the study funder, and data analysts were masked to treatment allocation. The primary endpoint was the annual asthma exacerbation rate at week 52 in the intention-to-treat population. Key secondary endpoints included prebronchodilator forced expiratory volume in 1 s (FEV 1 ), Asthma Control Questionnaire-6 (ACQ-6), and Asthma Quality of Life Questionnaire–Standardised Version (AQLQ[S]). This trial is registered with ClinicalTrials.gov , number NCT01402986 . Findings Between Oct 4, 2011, and Feb 22, 2014, we randomly assigned 452 patients to receive placebo (n=151) or tralokinumab every 2 weeks (n=150) or every 4 weeks (n=151), of whom 383 (85%) completed the treatment period up to week 52. The annual asthma exacerbation rate at week 52 was similar between patients receiving tralokinumab every 2 weeks (0·91 per patient per year [95% CI 0·76–1·08]) and every 4 weeks (0·97 [0·81–1·14]), and those receiving placebo (0·90 [0·75–1·08]). At week 52, percentage changes in annual asthma exacerbation rate were not significant with tralokinumab every 2 weeks or every 4 weeks versus placebo (6% [95% CI −31 to 33; p=0·709] and −2% [–46 to 29; p=0·904], respectively), with positive changes showing a decrease in exacerbation rate and negative changes showing an increase. Prebronchodilator FEV 1 was significantly increased compared with placebo for tralokinumab every 2 weeks (change from baseline 7·3% [95% CI 2·6–12·0]; p=0·003), but not every 4 weeks (1·8% [–2·9 to 6·6]; p=0·448); however, we did not identify significant changes in the other key secondary endpoints. In a post-hoc subgroup analysis of patients not on long-term oral corticosteroids and with baseline FEV 1 reversibility of 12% or greater, we noted a non-significant improvement in asthma exacerbation rate (44% [95% CI −22 to 74]; p=0·147) and significant improvements in key secondary endpoints (FEV 1 12·2% [1·7–22·7]; p=0·022; ACQ-6 −0·55 [–1·07 to −0·04]; p=0·036; and AQLQ[S] 0·70 [0·12–1·28]; p=0·019) in patients given tralokinumab every 2 weeks (n=33) compared with placebo (n=48). In patients in this subgroup who also had baseline serum dipeptidyl peptidase-4 (DPP-4) higher than the population baseline median, we noted additional improvements in prebronchodilator FEV 1 , ACQ-6, and AQLQ(S), and, in those with periostin concentrations higher than the median, we noted improvements in asthma exacerbation rate, prebronchodilator FEV 1 , and ACQ-6. The incidence of treatment-emergent adverse events was similar between the tralokinumab and placebo groups. Treatment-emergent serious adverse events regarded as related to the study drug were pneumonia (one [1%] patient in the placebo group), pneumococcal pneumonia (one [1%] in the tralokinumab every 2 weeks group), angioedema (one [1%] in the placebo group), and worsening asthma (one [1%] in the tralokinumab every 2 weeks group and two [1%] in the tralokinumab every 4 weeks group). Interpretation In this phase 2b study, both tralokinumab regimens had an acceptable safety and tolerability profile but did not significantly reduce asthma exacerbation rates in patients with severe uncontrolled asthma. Improvement in FEV 1 with tralokinumab given every 2 weeks and results of post-hoc subgroup analyses suggested a possible treatment effect in a defined population of patients with severe uncontrolled asthma. This effect is being further investigated in ongoing phase 3 trials, along with the potential utility of DPP-4 and periostin as biomarkers of interleukin-13 pathway activation. Funding MedImmune. [ABSTRACT FROM AUTHOR]
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- 2015
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15. Efficacy and safety of tralokinumab in patients with severe uncontrolled asthma: a randomised, double-blind, placebo-controlled, phase 2b trial
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Brightling, Christopher E, Chanez, Pascal, Leigh, Richard, O'Byrne, Paul M, Korn, Stephanie, She, Dewei, May, Richard D, Streicher, Katie, Ranade, Koustubh, and Piper, Edward
- Abstract
Interleukin 13 is a central mediator of asthma. Tralokinumab is a human interleukin-13 neutralising monoclonal antibody. We aimed to assess the efficacy and safety of two dosing regimens of tralokinumab in patients with severe uncontrolled asthma.
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- 2015
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16. The SARS-CoV-2 monoclonal antibody combination, AZD7442, is protective in nonhuman primates and has an extended half-life in humans
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Loo, Yueh-Ming, McTamney, Patrick M., Arends, Rosalinda H., Abram, Michael E., Aksyuk, Anastasia A., Diallo, Seme, Flores, Daniel J., Kelly, Elizabeth J., Ren, Kuishu, Roque, Richard, Rosenthal, Kim, Streicher, Katie, Tuffy, Kevin M., Bond, Nicholas J., Cornwell, Owen, Bouquet, Jerome, Cheng, Lily I., Dunyak, James, Huang, Yue, Rosenbaum, Anton I., Pilla Reddy, Venkatesh, Andersen, Hanne, Carnahan, Robert H., Crowe, James E., Kuehne, Ana I., Herbert, Andrew S., Dye, John M., Bright, Helen, Kallewaard, Nicole L., Pangalos, Menelas N., and Esser, Mark T.
- Abstract
Despite the success of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, there remains a need for more prevention and treatment options for individuals remaining at risk of coronavirus disease 2019 (COVID-19). Monoclonal antibodies (mAbs) against the viral spike protein have potential to both prevent and treat COVID-19 and reduce the risk of severe disease and death. Here, we describe AZD7442, a combination of two mAbs, AZD8895 (tixagevimab) and AZD1061 (cilgavimab), that simultaneously bind to distinct, nonoverlapping epitopes on the spike protein receptor binding domain to neutralize SARS-CoV-2. Initially isolated from individuals with prior SARS-CoV-2 infection, the two mAbs were designed to extend their half-lives and reduce effector functions. The AZD7442 mAbs individually prevent the spike protein from binding to angiotensin-converting enzyme 2 receptor, blocking virus cell entry, and neutralize all tested SARS-CoV-2 variants of concern. In a nonhuman primate model of SARS-CoV-2 infection, prophylactic AZD7442 administration prevented infection, whereas therapeutic administration accelerated virus clearance from the lung. In an ongoing phase 1 study in healthy participants (NCT04507256), a 300-mg intramuscular injection of AZD7442 provided SARS-CoV-2 serum geometric mean neutralizing titers greater than 10-fold above those of convalescent serum for at least 3 months, which remained threefold above those of convalescent serum at 9 months after AZD7442 administration. About 1 to 2% of serum AZD7442 was detected in nasal mucosa, a site of SARS-CoV-2 infection. Extrapolation of the time course of serum AZD7442 concentration suggests AZD7442 may provide up to 12 months of protection and benefit individuals at high-risk of COVID-19.
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- 2022
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17. Efficacy and safety of intramuscular administration of tixagevimab–cilgavimab for early outpatient treatment of COVID-19 (TACKLE): a phase 3, randomised, double-blind, placebo-controlled trial
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Montgomery, Hugh, Hobbs, F D Richard, Padilla, Francisco, Arbetter, Douglas, Templeton, Alison, Seegobin, Seth, Kim, Kenneth, Campos, Jesus Abraham Simón, Arends, Rosalinda H, Brodek, Bryan H, Brooks, Dennis, Garbes, Pedro, Jimenez, Julieta, Koh, Gavin C K W, Padilla, Kelly W, Streicher, Katie, Viani, Rolando M, Alagappan, Vijay, Pangalos, Menelas N, Esser, Mark T, Abe, Wakana, Adan De Varona, Tania, Adiatullina, Daria, Aguilar Zapata, Daniel, Ahlers, Kevin, Aimo, Carolina, Akere, Ayoade, Akimova, Elena, Alatorre Alexander, Jorge, Aldrich, Logan, Ali Garcia, Ismael, Ali García, Karim, Allison, Lee, Alonso Zuñiga, Rosa, Aloysius, Ivan, Altclas, Javier, Alvarisqueta, Andres, Antila, Martti, Anton, Camila, Árboix Alamo, Elisabet, Arora, Samir, Avilés Felix, Ramón Alejandro, Bakhtina, Natalya, Barbero-Becerra, Varenka, Barragan-Reyes, Armando, Barreira, Alejandro, Barrett, Mitchell, Beran, Jiri, Berki, Nikolett, Berki, Viktoria, Betten, Richard, Binelli, Claudia, Brunzová, Lenka, Bussolari, Cecilia, Byargeon, Karianna, Bytnar, Justyna, Camberos, Carlos, Campos Corzo, Pedro, Cannon, Grazia, Canovi, Valentina, Carla da Rosa, Simone, Moser, Ana Caroline, Carrera Rivas, Luis, Casas, Marcelo Martin, Castañeda-Méndez, Paulo, Cavalcante, Ana, Cherepova, Eugenia, Chermenskii, Alexei, Clark, Lauren, Codeluppi, Mauro, Coelho, Flavia, Contreras, Belinda, Cran, Alex, Dao, Taylor, Dharma, Chrisette, Di Castri, Cosimo, Diaz Balocchi, Victoria, Durán, Omar, Earl, Kara, Ellery, Adam, Endo, Tomoko, Everding, Andrea, Fischer, Rainald, Fonseca, Benedito, Franklin, Chelsea C., Franz, Susan-Beatrice, Fumagalli, Anna, Galindo-Amaya, Mauricio, Galli, Mariagiulia, Gerna, Laura, Gil Ureña, Karolly, Gomes Antila, Henrikki, Gomes Maricato, Laura Ines, Goncalvez, Gabriela, Gonzalez, Martin, González-Lama, Jesús, Granier, Stephen, Granier, Jacob, Grunwald, Stephan, Guardeño-Ropero, David, Guberti, Monica, Guduri, Sridhar, Guerrero García, Carolina, Haggiagi, Jehad, Hale, Kacie, Hayashi, Toshimasa, Hermes, Maiara, Hernandez Colin, Dante, Hirai, Yuji, Hojo, Masayuki, Homma, Tetsuya, Hour, Billy, Huber, Andreas, Iacovelli, Diego, Ishibashi, Noriomi, Iwabe, Yutaro, Izumi, Shinyu, Jessen, Arne, Jessen, Heiko, Jeudy, Wilner, Jiménez Marcos, Marta, Johnson, Rebecca, Juárez-Hernández, Eva, Kabasawa, Kiyomi, Kamińska, Katarzyna, Kawabe, Megumi, Kemp, Angela, Khmelnitskiy, Oleg, Klassen, Carina, Kobrynska, Olena, Koleckar, Pavel, Korn, Stephanie, Kornmann, Marc, Kostenko, Viktor, Kovalchuk, Evgenii, Kovalchuk, Yana, Kümmerle, Tim, Lachmund, Ulrike, Lammersmann, Kerstin, Lastebasse, Flávio, Lattuada, Ivana, Lauer, Felicitas, Lebed, Kyrylo, Lebed, Olga, Lecona-Garcia, Diego, Leoni, Maria Christina, Lima, Marina, Little, Raymond, Little, Holly, Lizardi-Díaz, Andrea, Lobo-Becker, Michele, Luppi, Francesco, Macias, Veronica, Maesaki, Shigefumi, Magnaghi, Cristiano, Mancini, Annalisa, Mazur, Stanisław, Melnikova, Tatiana, Menchaca, Sergio, Menendez-Perez, Ibrahim, Międlar, Ewa, Mizunuma, Shuuichi, Mochalova, Anastasiya, Mohamed, Mihad, Moll, Theresa, Montalvo, Camila, Mottola, Amber, Mück, Birgit, Mussi Brugnolli, Rebeca, Nanda, Akanksha, Neuner, Dörthe, Ngwueke, Agatha, Noe, Sebastian, Novacek, Martin, Nuzzolo-Shihadeh, Laura, Obiekwe, Emeka, Ocampo Gaytán, Isaias G., Ohmagari, Norio, Ohta, Shin, Onyewuchi, Ptuonye, Pankov, Iurii, Pedrosa, Maurício, Peré, Yael, Pereyra, Alejandro, Perez, Eliana, Perez-Alba, Eduardo, Perpiña Lozano, Paloma, Perrei, Tanya, Peterson, Dena, Pierroti, Ligia, Pineda-Cárdenas, Felipe, Plascencia Sanchez, Teresa, Poletti, Camila, Pomaranzi, Chiara, Portes, Lisette, Postel, Nils, Ramirez, Monica, Ramírez, Isabel, Ramirez-Baena, Miguel, Ramjee, Mahadev, Ratti, Giovanna, Reeve, Jackie, Reichert, Petr, Reichertová, Petra, Reyes Garcia, Edgar Alejandro, Ricardo, Celso, Rodríguez Rodríguez, Nicomedes, Roldán Sánchez, Jaun, Romero-Lopez, Matilde, Rosales, Tyrone, Rosales, Harvey, Roshan, Mohamed, Roshan, Simran, Rovere Querini, Patrizia, Rutter, Heather, Sachwani, Sadaf, Sagara, Hironori, Sakai, Jun, Samson, Nina, Sánchez Mijangos, José Héctor, Sánchez, Liliana, Sánchez-González, Ana, Sandford, Micko, Santana, Laura, Santos de Carvalho, Felipe, Sasao, Reiko, Sato, Lubna, Scheuermann, Elizabeth, Schmidt, Olaf, Seki, Masafumi, Shaikh, Safia, Shimada, Daishi, Shinkai, Masaharu, Shinoda, Masahiro, Smith, Jackie, Solorzano, Fernando, Soncini, Silvia, Soregine, Katalin, Sosa, Erica, Sowade, Olalekan, Špinková, Veronika, Staniford, Ruth, Steigemann, Iska, Steiner, Vivien, Strelkov, Vladimir, Suárez Pineda, Cintya R., Suenaga, Hiroki, Suzaki, Shintaro, Swayze, Hannah, Tada, Yuji, Takeshita, Yuichiro, Takiguchi, Yasuo, Tanaka, Akihiko, Tarumoto, Norihito, Tatarintseva, Albina, Taubert, Michelle, Terenya, Elizaveta, Tinoco, César, Tomiyasu, Tomohiro, Torres-Vidal, Gladys, Trejo-Aguiar, Gabriela, Tsushima, Kenji, Tunstall, Emma, Turrà, Caterina, Valdes, Yoandy, Valencia Castro, Nelly, Visconti, Guilherme, Vitali, Giordano, Vutikullird, Apinya, Watti, Jezdancher, Werth, Doreen, Wilson, Cheyanne, Wilson, Philippe, Workman, Amy, Wörle, Pamela, Wyen, Christoph, Yamaguchi, Yoshiko, and Yamamoto, Kei
- Abstract
Early intramuscular administration of SARS-CoV-2-neutralising monoclonal antibody combination, tixagevimab–cilgavimab, to non-hospitalised adults with mild to moderate COVID-19 has potential to prevent disease progression. We aimed to evaluate the safety and efficacy of tixagevimab–cilgavimab in preventing progression to severe COVID-19 or death.
- Published
- 2022
- Full Text
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18. Mammary Gland Immunity and Mastitis Susceptibility
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Sordillo, Lorraine and Streicher, Katie
- Abstract
Lactation is considered the final phase of the mammalian reproductive cycle, and the mammary gland provides milk for nourishment and disease resistance to the newborn. However, the cellular and soluble immune components associated with mammary tissues and secretion also can play an important role in protecting the gland from infectious diseases, such as mastitis. Mastitis can affect essentially all lactating mammals, but is especially problematic for dairy cattle. The most recent estimates from the National Mastitis Council suggest that mastitis affects one third of all dairy cows and will cost the dairy industry over 2 billion dollars annually in the United States in lost profits (National Mastitis Council (1996) Current Concepts in Bovine Mastitis, National Mastitis Council, Madison, WI). The overall impact of mastitis on the quality and quantity of milk produced for human consumption has provided the impetus to better understand the pathophysiology of the mammary gland and develop ways to enhance disease resistance through immunoregulation. As such, the bovine species has played a critical and prominent role in our current understanding of mammary gland immunobiology. This paper provides a comprehensive overview of mammary gland immunity and how the stage of lactation can impact important host defenses. While this review emphasizes the bovine system, comparisons to humans and other domestic mammals will be addressed as well.
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- 2002
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19. A CD40L-targeting protein reduces autoantibodies and improves disease activity in patients with autoimmunity
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Karnell, Jodi L., Albulescu, Marius, Drabic, Stacey, Wang, Liangwei, Moate, Rachel, Baca, Manuel, Oganesyan, Vaheh, Gunsior, Michele, Thisted, Thomas, Yan, Li, Li, Jing, Xiong, Ximing, Eck, Steven C., de los Reyes, Melissa, Yusuf, Isharat, Streicher, Katie, Müller-Ladner, Ulf, Howe, David, Ettinger, Rachel, Herbst, Ronald, and Drappa, Jörn
- Abstract
VIB4920, a nonantibody scaffold protein, blocks CD40L and reduces autoantibodies and disease activity in patients with rheumatoid arthritis.
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- 2019
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20. A microRNA Signature Predicts Response to Anti-CD19 Therapy (MEDI-551) in B-Cell Malignancies
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Streicher, Katie, Brohawn, Philip, Kuziora, Mike, Pilataxi, Fernanda, Higgs, Brandon, Lehmann, Kim, McKeever, Kathleen, Goswami, Trishna, Herbst, Ronald, Yao, Yihong, and Ranade, Koustubh
- Abstract
Streicher: MedImmune: Employment; MedImmune: Stock ownership, Stock ownership Other. Brohawn:MedImmune: Employment, Equity Ownership. Kuziora:MedImmune: Employment, Equity Ownership. Pilataxi:MedImmune: Employment, Equity Ownership. Higgs:MedImmune: Employment, Equity Ownership. Lehmann:MedImmune: Employment, Equity Ownership. McKeever:MedImmune: Employment, Equity Ownership. Goswami:MedImmune: Employment; MedImmune: Stock ownership, Stock ownership Other. Herbst:MedImmune: Employment, Equity Ownership. Yao:MedImmune: Employment, Equity Ownership. Ranade:MedImmune: Employment, Equity Ownership.
- Published
- 2014
- Full Text
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21. Results of a Phase 2 Study of MEDI-551 and Bendamustine Vs Rituximab and Bendamustine in Relapsed or Refractory Chronic Lymphocytic Leukemia
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Gladstone, Douglas, Andre, Marc, Zaucha, Jan, Assouline, Sarit, Bellam, Naresh, Cascavilla, Nicole, Jourdan, Eric, Panwalkar, Amit, Patti, Caterina, Schulte, Clemens, Zaja, Francesco, Goswami, Trishna, Elgeioushi, Nairouz, Streicher, Katie, Bao, Haifeng, and Spaner, David
- Abstract
Gladstone: MedImmune: Research Funding. Andre:MedImmune: Research Funding. Zaucha:MedImmune: Research Funding. Assouline:MedImmune: Research Funding. Bellam:Genentech: Research Funding; Janssen: Research Funding; MedImmune: Research Funding; Facet: Research Funding. Cascavilla:MedImmune: Research Funding. Jourdan:MedImmune: Research Funding; Roche: Research Funding. Panwalkar:MedImmune: Research Funding. Patti:MedImmune: Research Funding. Zaja:MedImmune: Research Funding. Goswami:MedImmune: Employment; MedImmune: Stock ownership, Stock ownership Other. Elgeioushi:MedImmune: Employment; MedImmune: Stock ownership, Stock ownership Other. Streicher:MedImmune: Employment; MedImmune: Stock ownership, Stock ownership Other. Bao:MedImmune: Employment; MedImmune: Stock ownership, Stock ownership Other. Spaner:MedImmune: Research Funding.
- Published
- 2014
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22. A microRNA Signature Predicts Response to Anti-CD19 Therapy (MEDI-551) in B-Cell Malignancies
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Streicher, Katie, Brohawn, Philip, Kuziora, Mike, Pilataxi, Fernanda, Higgs, Brandon, Lehmann, Kim, McKeever, Kathleen, Goswami, Trishna, Herbst, Ronald, Yao, Yihong, and Ranade, Koustubh
- Abstract
Background:
- Published
- 2014
- Full Text
- View/download PDF
23. Results of a Phase 2 Study of MEDI-551 and Bendamustine Vs Rituximab and Bendamustine in Relapsed or Refractory Chronic Lymphocytic Leukemia
- Author
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Gladstone, Douglas, Andre, Marc, Zaucha, Jan, Assouline, Sarit, Bellam, Naresh, Cascavilla, Nicole, Jourdan, Eric, Panwalkar, Amit, Patti, Caterina, Schulte, Clemens, Zaja, Francesco, Goswami, Trishna, Elgeioushi, Nairouz, Streicher, Katie, Bao, Haifeng, and Spaner, David
- Abstract
Background: In patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL), novel therapies are needed to prolong disease control. MEDI-551, an afucoslylated, affinity-optimized, anti-CD19 antibody, functions by antibody-dependent cellular cytotoxicity, with a 30% monotherapy response rate in CLL. A phase 2 randomized, open-label study (NCT01466153) is evaluating the clinical activity, efficacy, and safety of combination therapy with MEDI-551 + bendamustine compared with rituximab + bendamustine in R/R CLL patients.
- Published
- 2014
- Full Text
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