20 results on '"Diacon A"'
Search Results
2. Treatment of Highly Drug-Resistant Pulmonary Tuberculosis
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Francesca, Conradie, Andreas H, Diacon, Nosipho, Ngubane, Pauline, Howell, Daniel, Everitt, Angela M, Crook, Carl M, Mendel, Erica, Egizi, Joanna, Moreira, Juliano, Timm, Timothy D, McHugh, Genevieve H, Wills, Anna, Bateson, Robert, Hunt, Christo, Van Niekerk, Mengchun, Li, Morounfolu, Olugbosi, Melvin, Spigelman, and Priya, Solanki
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Adult ,Male ,medicine.medical_specialty ,Tuberculosis ,Adolescent ,Extensively Drug-Resistant Tuberculosis ,Antitubercular Agents ,Administration, Oral ,Drug resistance ,030204 cardiovascular system & hematology ,Article ,Young Adult ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Pharmacotherapy ,Tuberculosis, Multidrug-Resistant ,medicine ,Humans ,030212 general & internal medicine ,Diarylquinolines ,Intensive care medicine ,Tuberculosis, Pulmonary ,Intention-to-treat analysis ,business.industry ,Linezolid ,Extensively drug-resistant tuberculosis ,Mycobacterium tuberculosis ,General Medicine ,Middle Aged ,medicine.disease ,Bacterial Load ,Intention to Treat Analysis ,3. Good health ,Multiple drug resistance ,Clinical trial ,Treatment Outcome ,chemistry ,Nitroimidazoles ,Pretomanid ,Drug Therapy, Combination ,Female ,business - Abstract
Patients with highly drug-resistant forms of tuberculosis have limited treatment options and historically have had poor outcomes.In an open-label, single-group study in which follow-up is ongoing at three South African sites, we investigated treatment with three oral drugs - bedaquiline, pretomanid, and linezolid - that have bactericidal activity against tuberculosis and to which there is little preexisting resistance. We evaluated the safety and efficacy of the drug combination for 26 weeks in patients with extensively drug-resistant tuberculosis and patients with multidrug-resistant tuberculosis that was not responsive to treatment or for which a second-line regimen had been discontinued because of side effects. The primary end point was the incidence of an unfavorable outcome, defined as treatment failure (bacteriologic or clinical) or relapse during follow-up, which continued until 6 months after the end of treatment. Patients were classified as having a favorable outcome at 6 months if they had resolution of clinical disease, a negative culture status, and had not already been classified as having had an unfavorable outcome. Other efficacy end points and safety were also evaluated.A total of 109 patients were enrolled in the study and were included in the evaluation of efficacy and safety end points. At 6 months after the end of treatment in the intention-to-treat analysis, 11 patients (10%) had an unfavorable outcome and 98 patients (90%; 95% confidence interval, 83 to 95) had a favorable outcome. The 11 unfavorable outcomes were 7 deaths (6 during treatment and 1 from an unknown cause during follow-up), 1 withdrawal of consent during treatment, 2 relapses during follow-up, and 1 loss to follow-up. The expected linezolid toxic effects of peripheral neuropathy (occurring in 81% of patients) and myelosuppression (48%), although common, were manageable, often leading to dose reductions or interruptions in treatment with linezolid.The combination of bedaquiline, pretomanid, and linezolid led to a favorable outcome at 6 months after the end of therapy in a high percentage of patients with highly drug-resistant forms of tuberculosis; some associated toxic effects were observed. (Funded by the TB Alliance and others; ClinicalTrials.gov number, NCT02333799.).
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- 2020
3. Telacebec (Q203), a New Antituberculosis Agent
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de Jager, Veronique R., primary, Dawson, Rodney, additional, van Niekerk, Christo, additional, Hutchings, Jane, additional, Kim, Jeongjun, additional, Vanker, Naadira, additional, van der Merwe, Lize, additional, Choi, Jinho, additional, Nam, Kiyean, additional, and Diacon, Andreas H., additional
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- 2020
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4. Treatment of Highly Drug-Resistant Pulmonary Tuberculosis
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Conradie, Francesca, primary, Diacon, Andreas H., additional, Ngubane, Nosipho, additional, Howell, Pauline, additional, Everitt, Daniel, additional, Crook, Angela M., additional, Mendel, Carl M., additional, Egizi, Erica, additional, Moreira, Joanna, additional, Timm, Juliano, additional, McHugh, Timothy D., additional, Wills, Genevieve H., additional, Bateson, Anna, additional, Hunt, Robert, additional, Van Niekerk, Christo, additional, Li, Mengchun, additional, Olugbosi, Morounfolu, additional, and Spigelman, Melvin, additional
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- 2020
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5. Final Analysis of a Trial of M72/AS01E Vaccine to Prevent Tuberculosis
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Tait, Dereck R., primary, Hatherill, Mark, additional, Van Der Meeren, Olivier, additional, Ginsberg, Ann M., additional, Van Brakel, Elana, additional, Salaun, Bruno, additional, Scriba, Thomas J., additional, Akite, Elaine J., additional, Ayles, Helen M., additional, Bollaerts, Anne, additional, Demoitié, Marie-Ange, additional, Diacon, Andreas, additional, Evans, Thomas G., additional, Gillard, Paul, additional, Hellström, Elizabeth, additional, Innes, James C., additional, Lempicki, Maria, additional, Malahleha, Mookho, additional, Martinson, Neil, additional, Mesia Vela, Doris, additional, Muyoyeta, Monde, additional, Nduba, Videlis, additional, Pascal, Thierry G., additional, Tameris, Michele, additional, Thienemann, Friedrich, additional, Wilkinson, Robert J., additional, and Roman, François, additional
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- 2019
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6. Telacebec (Q203), a New Antituberculosis Agent
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Rodney Dawson, Jeongjun Kim, Veronique R. de Jager, Jinho Choi, Jane Hutchings, Kiyean Nam, Naadira Vanker, Christo van Niekerk, Andreas H. Diacon, and Lize van der Merwe
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Drug ,Tuberculosis ,biology ,business.industry ,media_common.quotation_subject ,Antituberculosis agent ,General Medicine ,030204 cardiovascular system & hematology ,Pharmacology ,biology.organism_classification ,medicine.disease ,Mycobacterium tuberculosis ,03 medical and health sciences ,0302 clinical medicine ,Medicine ,030212 general & internal medicine ,Cellular energy ,business ,media_common - Abstract
Telacebec (Q203), a New Antituberculosis Agent Telacebec (Q203) is a novel drug that targets Mycobacterium tuberculosis cellular energy production through inhibition of the mycobacterial cytochrome...
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- 2020
7. Phase 2b Controlled Trial of M72/AS01EVaccine to Prevent Tuberculosis
- Author
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Van Der Meeren, Olivier, primary, Hatherill, Mark, additional, Nduba, Videlis, additional, Wilkinson, Robert J., additional, Muyoyeta, Monde, additional, Van Brakel, Elana, additional, Ayles, Helen M., additional, Henostroza, German, additional, Thienemann, Friedrich, additional, Scriba, Thomas J., additional, Diacon, Andreas, additional, Blatner, Gretta L., additional, Demoitié, Marie-Ange, additional, Tameris, Michele, additional, Malahleha, Mookho, additional, Innes, James C., additional, Hellström, Elizabeth, additional, Martinson, Neil, additional, Singh, Tina, additional, Akite, Elaine J., additional, Khatoon Azam, Aisha, additional, Bollaerts, Anne, additional, Ginsberg, Ann M., additional, Evans, Thomas G., additional, Gillard, Paul, additional, and Tait, Dereck R., additional
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- 2018
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8. The Diarylquinoline TMC207 for Multidrug-Resistant Tuberculosis
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Liesl Page-Shipp, Jenny Allen, Paul Meyvisch, Karel de Beule, Alexander S. Pym, Rene Krause, Andreas H. Diacon, Johan Verbeeck, Koen Andries, Martin P. Grobusch, Roxana Rustomjee, Nacer Lounis, Rolf van Heeswijk, R. F. Patientia, Juan Carlos Palomino, Christoffel Pistorius, Amour Venter, David F Mc Neeley, Tine De Marez, Wim Parys, Gavin J. Churchyard, Mampedi Bogoshi, and Infectious diseases
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Male ,Antitubercular Agents ,Colony Count, Microbial ,SQ109 ,Multidrug resistance ,Gastroenterology ,chemistry.chemical_compound ,Clinical trials ,Tuberculosis, Multidrug-Resistant ,Diarylquinoline TMC207 ,Diarylquinolines ,medicine.diagnostic_test ,biology ,General Medicine ,Middle Aged ,Proton-Translocating ATPases ,Quinolines ,Drug Therapy, Combination ,Female ,Second-line drugs ,Delamanid ,medicine.symptom ,medicine.drug ,Adult ,medicine.medical_specialty ,Tuberculosis ,Adolescent ,Efficacy ,Bacterial diseases ,Drug development ,Microbial Sensitivity Tests ,Article ,Sputum culture ,Mycobacterium tuberculosis ,Young Adult ,Internal medicine ,medicine ,Humans ,business.industry ,medicine.disease ,biology.organism_classification ,chemistry ,Pretomanid ,Immunology ,Sputum ,Human medicine ,Bedaquiline ,business - Abstract
Background The diarylquinoline TMC207 offers a new mechanism of antituberculosis action by inhibiting mycobacterial ATP synthase. TMC207 potently inhibits drug-sensitive and drug-resistant Mycobacterium tuberculosis in vitro and shows bactericidal activity in patients who have drug-susceptible pulmonary tuberculosis. Methods In the first stage of a two-stage, phase 2, randomized, controlled trial, we randomly assigned 47 patients who had newly diagnosed multidrug-resistant pulmonary tuberculosis to receive either TMC207 (400 mg daily for 2 weeks, followed by 200 mg three times a week for 6 weeks) (23 patients) or placebo (24 patients) in combination with a standard five-drug, second-line antituberculosis regimen. The primary efficacy end point was the conversion of sputum cultures, in liquid broth, from positive to negative. Results The addition of TMC207 to standard therapy for multidrug-resistant tuberculosis reduced the time to conversion to a negative sputum culture, as compared with placebo (hazard ratio, 11.8; 95% confidence interval, 2.3 to 61.3; P=0.003 by Cox regression analysis) and increased the proportion of patients with conversion of sputum culture (48% vs. 9%). The mean log10 count of colony-forming units in the sputum declined more rapidly in the TMC207 group than in the placebo group. No significant differences in average plasma TMC207 concentrations were noted between patients with and those without culture conversion. Most adverse events were mild to moderate, and only nausea occurred significantly more frequently among patients in the TMC207 group than among patients in the placebo group (26% vs. 4%, P=0.04). Conclusions The clinical activity of TMC207 validates ATP synthase as a viable target for the treatment of tuberculosis. (ClinicalTrials.gov number, NCT00449644 [ClinicalTrials.gov] .)
- Published
- 2009
9. β-Lactams against Tuberculosis — New Trick for an Old Dog?
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Alberto L. García-Basteiro, Florian von Groote-Bidlingmaier, Esperança Sevene, Andreas H. Diacon, Lize van der Merwe, Christoph Lange, David Barros-Aguirre, Lluis Ballell, and Marinus Barnard
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0301 basic medicine ,medicine.medical_specialty ,Tuberculosis ,030106 microbiology ,Antitubercular Agents ,Colony Count, Microbial ,Amoxicillin-Potassium Clavulanate Combination ,beta-Lactams ,Beta-lactam ,Mycobacterium tuberculosis ,03 medical and health sciences ,chemistry.chemical_compound ,ANTIRETROVIRAL AGENTS ,Drug Discovery ,Tuberculosis, Multidrug-Resistant ,β lactams ,medicine ,Humans ,Intensive care medicine ,Beta-Lactamase Inhibitors ,Repurposing ,biology ,business.industry ,Isoniazid ,General Medicine ,biology.organism_classification ,medicine.disease ,Surgery ,chemistry ,beta-Lactamase Inhibitors ,business ,medicine.drug - Abstract
To the Editor: New treatments are needed to combat the worldwide increase in resistance to antituberculosis drugs.1 The outlook for patients with tuberculosis who do not show a response to the key agents used in treatment — isoniazid, rifampin, fluoroquinolones, and aminoglycosides — is grim and reminiscent of the plight of patients with cancer in the era before chemotherapy.2 New agents are emerging, but the obligatory evaluation of their safety and efficacy in combination with other antituberculosis and antiretroviral agents slows the pace of progress. Repurposing or combining commercially available products may offer a faster track to new antituberculosis regimens. . . .
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- 2016
10. β-Lactams against Tuberculosis — New Trick for an Old Dog?
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Diacon, Andreas H., primary, van der Merwe, Lize, additional, Barnard, Marinus, additional, von Groote-Bidlingmaier, Florian, additional, Lange, Christoph, additional, García-Basteiro, Alberto L., additional, Sevene, Esperança, additional, Ballell, Lluís, additional, and Barros-Aguirre, David, additional
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- 2016
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11. Multidrug-Resistant Tuberculosis and Culture Conversion with Bedaquiline
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Diacon, Andreas H., primary, Pym, Alexander, additional, Grobusch, Martin P., additional, de los Rios, Jorge M., additional, Gotuzzo, Eduardo, additional, Vasilyeva, Irina, additional, Leimane, Vaira, additional, Andries, Koen, additional, Bakare, Nyasha, additional, De Marez, Tine, additional, Haxaire-Theeuwes, Myriam, additional, Lounis, Nacer, additional, Meyvisch, Paul, additional, De Paepe, Els, additional, van Heeswijk, Rolf P.G., additional, and Dannemann, Brian, additional
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- 2014
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12. The Diarylquinoline TMC207 for Multidrug-Resistant Tuberculosis
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Diacon, Andreas H., primary, Pym, Alexander, additional, Grobusch, Martin, additional, Patientia, Ramonde, additional, Rustomjee, Roxana, additional, Page-Shipp, Liesl, additional, Pistorius, Christoffel, additional, Krause, Rene, additional, Bogoshi, Mampedi, additional, Churchyard, Gavin, additional, Venter, Amour, additional, Allen, Jenny, additional, Palomino, Juan Carlos, additional, De Marez, Tine, additional, van Heeswijk, Rolf P.G., additional, Lounis, Nacer, additional, Meyvisch, Paul, additional, Verbeeck, Johan, additional, Parys, Wim, additional, de Beule, Karel, additional, Andries, Koen, additional, and Neeley, David F. Mc, additional
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- 2009
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13. TO THE EDITOR.
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Diacon, Andreas H., Van Baelen, Ben, and Theeuwes, Myriam
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TUBERCULOSIS treatment , *MULTIDRUG resistance - Abstract
A letter to the editor is presented in response to the article "Treatment outcomes in multidrug-resistant tuberculosis" by G. Günther and colleagues which appeared in the September 15, 2016 issue.
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- 2016
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14. Multidrug-resistant tuberculosis and bedaquiline.
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Diacon, Andreas H, Lounis, Nacer, and Dannemann, Brian
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- 2014
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15. A Trial of Intrapleural Streptokinase.
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Diacon, Andreas H., Koegelenberg, Coenraad F.N., and Bolliger, Chris T.
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LETTERS to the editor , *STREPTOKINASE - Abstract
A letter to the editor is presented in response to an article by Nicholas A. Maskell and colleagues about a controlled trial of intrapleural streptokinase in the March 3, 2005 issue.
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- 2005
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16. A trial of intrapleural streptokinase.
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Katikireddy CK, Dube DS, Diacon AH, Koegelenberg CFN, Bollinger CT, Rosa UW, Bouros D, Davies RJO, Maskell NA, Nunn AJ, Katikireddy, Chandra K, and Dube, Daniel S
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- 2005
17. Final Analysis of a Trial of M72/AS01E Vaccine to Prevent Tuberculosis.
- Author
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Tait, D. R., Hatherill, M., Van Der Meeren, O., Ginsberg, A. M., Van Brakel, E., Salaun, B., Scriba, T. J., Akite, E. J., Ayies, H. M., Bollaerts, A., Demoitié, M.-A., Diacon, A., Evans, T. G., Gillard, P., Hellstrom, E., Innes, J. C., Lempicki, M., Malahleha, M., Martinson, N., and Vela, D. Mesia
- Abstract
Background: Results of an earlier analysis of a trial of the M72/AS01E candidate vaccine against Mycobacterium tuberculosis showed that in infected adults, the vaccine provided 54.0% protection against active pulmonary tuberculosis disease, without evident safety concerns. We now report the results of the 3-year final analysis of efficacy, safety, and immunogenicity.Methods: From August 2014 through November 2015, we enrolled adults 18 to 50 years of age with M. tuberculosis infection (defined by positive results on interferon-γ release assay) without evidence of active tuberculosis disease at centers in Kenya, South Africa, and Zambia. Participants were randomly assigned in a 1:1 ratio to receive two doses of either M72/AS01E or placebo, administered 1 month apart. The primary objective was to evaluate the efficacy of M72/AS01E to prevent active pulmonary tuberculosis disease according to the first case definition (bacteriologically confirmed pulmonary tuberculosis not associated with human immunodeficiency virus infection). Participants were followed for 3 years after the second dose. Participants with clinical suspicion of tuberculosis provided sputum samples for polymerase-chain-reaction assay, mycobacterial culture, or both. Humoral and cell-mediated immune responses were evaluated until month 36 in a subgroup of 300 participants. Safety was assessed in all participants who received at least one dose of M72/AS01E or placebo.Results: A total of 3575 participants underwent randomization, of whom 3573 received at least one dose of M72/AS01E or placebo, and 3330 received both planned doses. Among the 3289 participants in the according-to-protocol efficacy cohort, 13 of the 1626 participants in the M72/AS01E group, as compared with 26 of the 1663 participants in the placebo group, had cases of tuberculosis that met the first case definition (incidence, 0.3 vs. 0.6 cases per 100 person-years). The vaccine efficacy at month 36 was 49.7% (90% confidence interval [CI], 12.1 to 71.2; 95% CI, 2.1 to 74.2). Among participants in the M72/AS01E group, the concentrations of M72-specific antibodies and the frequencies of M72-specific CD4+ T cells increased after the first dose and were sustained throughout the follow-up period. Serious adverse events, potential immune-mediated diseases, and deaths occurred with similar frequencies in the two groups.Conclusions: Among adults infected with M. tuberculosis, vaccination with M72/AS01E elicited an immune response and provided protection against progression to pulmonary tuberculosis disease for at least 3 years. (Funded by GlaxoSmithKline Biologicals and Aeras; ClinicalTrials.gov number, NCT01755598.). [ABSTRACT FROM AUTHOR]- Published
- 2019
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- View/download PDF
18. Phase 2b Controlled Trial of M72/AS01E Vaccine to Prevent Tuberculosis.
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Van Der Meeren, O., Hatherill, M., Nduba, V., Wilkinson, R. J., Muyoyeta, M., Van Brakel, E., Ayles, H. M., Henostroza, G., Scriba, T. J., Diacon, A., Blatner, G. L., Demoitié, M.-A., Tameris, M., Malahleha, M., Innes, J. C., Hellström, E., Martinson, N., Singh, T., Akite, E. J., and Khatoon Azam, A.
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TUBERCULOSIS prevention , *TUBERCULOSIS treatment , *BACTERIAL vaccines , *CLINICAL trials , *COMPARATIVE studies , *LONGITUDINAL method , *RESEARCH methodology , *MEDICAL cooperation , *MYCOBACTERIUM tuberculosis , *RESEARCH , *RESEARCH funding , *EVALUATION research , *RANDOMIZED controlled trials , *PROPORTIONAL hazards models , *BLIND experiment - Abstract
Background: A vaccine to interrupt the transmission of tuberculosis is needed.Methods: We conducted a randomized, double-blind, placebo-controlled, phase 2b trial of the M72/AS01E tuberculosis vaccine in Kenya, South Africa, and Zambia. Human immunodeficiency virus (HIV)-negative adults 18 to 50 years of age with latent M. tuberculosis infection (by interferon-γ release assay) were randomly assigned (in a 1:1 ratio) to receive two doses of either M72/AS01E or placebo intramuscularly 1 month apart. Most participants had previously received the bacille Calmette-Guérin vaccine. We assessed the safety of M72/AS01E and its efficacy against progression to bacteriologically confirmed active pulmonary tuberculosis disease. Clinical suspicion of tuberculosis was confirmed with sputum by means of a polymerase-chain-reaction test, mycobacterial culture, or both.Results: We report the primary analysis (conducted after a mean of 2.3 years of follow-up) of the ongoing trial. A total of 1786 participants received M72/AS01E and 1787 received placebo, and 1623 and 1660 participants in the respective groups were included in the according-to-protocol efficacy cohort. A total of 10 participants in the M72/AS01E group met the primary case definition (bacteriologically confirmed active pulmonary tuberculosis, with confirmation before treatment), as compared with 22 participants in the placebo group (incidence, 0.3 cases vs. 0.6 cases per 100 person-years). The vaccine efficacy was 54.0% (90% confidence interval [CI], 13.9 to 75.4; 95% CI, 2.9 to 78.2; P=0.04). Results for the total vaccinated efficacy cohort were similar (vaccine efficacy, 57.0%; 90% CI, 19.9 to 76.9; 95% CI, 9.7 to 79.5; P=0.03). There were more unsolicited reports of adverse events in the M72/AS01E group (67.4%) than in the placebo group (45.4%) within 30 days after injection, with the difference attributed mainly to injection-site reactions and influenza-like symptoms. Serious adverse events, potential immune-mediated diseases, and deaths occurred with similar frequencies in the two groups.Conclusions: M72/AS01E provided 54.0% protection for M. tuberculosis-infected adults against active pulmonary tuberculosis disease, without evident safety concerns. (Funded by GlaxoSmithKline Biologicals and Aeras; ClinicalTrials.gov number, NCT01755598 .). [ABSTRACT FROM AUTHOR]- Published
- 2018
- Full Text
- View/download PDF
19. Final Analysis of a Trial of M72/AS01 E Vaccine to Prevent Tuberculosis.
- Author
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Tait DR, Hatherill M, Van Der Meeren O, Ginsberg AM, Van Brakel E, Salaun B, Scriba TJ, Akite EJ, Ayles HM, Bollaerts A, Demoitié MA, Diacon A, Evans TG, Gillard P, Hellström E, Innes JC, Lempicki M, Malahleha M, Martinson N, Mesia Vela D, Muyoyeta M, Nduba V, Pascal TG, Tameris M, Thienemann F, Wilkinson RJ, and Roman F
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- Adolescent, Adult, Africa, Disease Progression, Double-Blind Method, Female, Follow-Up Studies, HIV Seronegativity, Humans, Latent Tuberculosis immunology, Male, Middle Aged, Proportional Hazards Models, Young Adult, Immunogenicity, Vaccine, Latent Tuberculosis therapy, Mycobacterium tuberculosis immunology, Tuberculosis Vaccines immunology, Tuberculosis, Pulmonary prevention & control
- Abstract
Background: Results of an earlier analysis of a trial of the M72/AS01
E candidate vaccine against Mycobacterium tuberculosis showed that in infected adults, the vaccine provided 54.0% protection against active pulmonary tuberculosis disease, without evident safety concerns. We now report the results of the 3-year final analysis of efficacy, safety, and immunogenicity., Methods: From August 2014 through November 2015, we enrolled adults 18 to 50 years of age with M. tuberculosis infection (defined by positive results on interferon-γ release assay) without evidence of active tuberculosis disease at centers in Kenya, South Africa, and Zambia. Participants were randomly assigned in a 1:1 ratio to receive two doses of either M72/AS01E or placebo, administered 1 month apart. The primary objective was to evaluate the efficacy of M72/AS01E to prevent active pulmonary tuberculosis disease according to the first case definition (bacteriologically confirmed pulmonary tuberculosis not associated with human immunodeficiency virus infection). Participants were followed for 3 years after the second dose. Participants with clinical suspicion of tuberculosis provided sputum samples for polymerase-chain-reaction assay, mycobacterial culture, or both. Humoral and cell-mediated immune responses were evaluated until month 36 in a subgroup of 300 participants. Safety was assessed in all participants who received at least one dose of M72/AS01E or placebo., Results: A total of 3575 participants underwent randomization, of whom 3573 received at least one dose of M72/AS01E or placebo, and 3330 received both planned doses. Among the 3289 participants in the according-to-protocol efficacy cohort, 13 of the 1626 participants in the M72/AS01E group, as compared with 26 of the 1663 participants in the placebo group, had cases of tuberculosis that met the first case definition (incidence, 0.3 vs. 0.6 cases per 100 person-years). The vaccine efficacy at month 36 was 49.7% (90% confidence interval [CI], 12.1 to 71.2; 95% CI, 2.1 to 74.2). Among participants in the M72/AS01E group, the concentrations of M72-specific antibodies and the frequencies of M72-specific CD4+ T cells increased after the first dose and were sustained throughout the follow-up period. Serious adverse events, potential immune-mediated diseases, and deaths occurred with similar frequencies in the two groups., Conclusions: Among adults infected with M. tuberculosis , vaccination with M72/AS01E elicited an immune response and provided protection against progression to pulmonary tuberculosis disease for at least 3 years. (Funded by GlaxoSmithKline Biologicals and Aeras; ClinicalTrials.gov number, NCT01755598.)., (Copyright © 2019 Massachusetts Medical Society.)- Published
- 2019
- Full Text
- View/download PDF
20. Phase 2b Controlled Trial of M72/AS01 E Vaccine to Prevent Tuberculosis.
- Author
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Van Der Meeren O, Hatherill M, Nduba V, Wilkinson RJ, Muyoyeta M, Van Brakel E, Ayles HM, Henostroza G, Thienemann F, Scriba TJ, Diacon A, Blatner GL, Demoitié MA, Tameris M, Malahleha M, Innes JC, Hellström E, Martinson N, Singh T, Akite EJ, Khatoon Azam A, Bollaerts A, Ginsberg AM, Evans TG, Gillard P, and Tait DR
- Subjects
- Adolescent, Adult, Africa, Double-Blind Method, Female, Follow-Up Studies, Humans, Male, Middle Aged, Proportional Hazards Models, Young Adult, Latent Tuberculosis therapy, Mycobacterium tuberculosis immunology, Tuberculosis prevention & control, Tuberculosis Vaccines adverse effects, Tuberculosis Vaccines immunology
- Abstract
Background: A vaccine to interrupt the transmission of tuberculosis is needed., Methods: We conducted a randomized, double-blind, placebo-controlled, phase 2b trial of the M72/AS01
E tuberculosis vaccine in Kenya, South Africa, and Zambia. Human immunodeficiency virus (HIV)-negative adults 18 to 50 years of age with latent M. tuberculosis infection (by interferon-γ release assay) were randomly assigned (in a 1:1 ratio) to receive two doses of either M72/AS01E or placebo intramuscularly 1 month apart. Most participants had previously received the bacille Calmette-Guérin vaccine. We assessed the safety of M72/AS01E and its efficacy against progression to bacteriologically confirmed active pulmonary tuberculosis disease. Clinical suspicion of tuberculosis was confirmed with sputum by means of a polymerase-chain-reaction test, mycobacterial culture, or both., Results: We report the primary analysis (conducted after a mean of 2.3 years of follow-up) of the ongoing trial. A total of 1786 participants received M72/AS01E and 1787 received placebo, and 1623 and 1660 participants in the respective groups were included in the according-to-protocol efficacy cohort. A total of 10 participants in the M72/AS01E group met the primary case definition (bacteriologically confirmed active pulmonary tuberculosis, with confirmation before treatment), as compared with 22 participants in the placebo group (incidence, 0.3 cases vs. 0.6 cases per 100 person-years). The vaccine efficacy was 54.0% (90% confidence interval [CI], 13.9 to 75.4; 95% CI, 2.9 to 78.2; P=0.04). Results for the total vaccinated efficacy cohort were similar (vaccine efficacy, 57.0%; 90% CI, 19.9 to 76.9; 95% CI, 9.7 to 79.5; P=0.03). There were more unsolicited reports of adverse events in the M72/AS01E group (67.4%) than in the placebo group (45.4%) within 30 days after injection, with the difference attributed mainly to injection-site reactions and influenza-like symptoms. Serious adverse events, potential immune-mediated diseases, and deaths occurred with similar frequencies in the two groups., Conclusions: M72/AS01E provided 54.0% protection for M. tuberculosis-infected adults against active pulmonary tuberculosis disease, without evident safety concerns. (Funded by GlaxoSmithKline Biologicals and Aeras; ClinicalTrials.gov number, NCT01755598 .).- Published
- 2018
- Full Text
- View/download PDF
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