Search

Your search keyword '"Skrinar, Alison"' showing total 158 results
Start Over Author "Skrinar, Alison"
158 results on '"Skrinar, Alison"'

1. Results from a 3-year Non-interventional, Observational Disease Monitoring Program in Adults with GNE Myopathy

Author

Lochmüller, Hanns, Behin, Anthony, Tournev, Ivailo, Tarnopolsky, Mark, Horváth, Rita, Pogoryelova, Oksana, Shah, Jinay, Koutsoukos, Tony, Skrinar, Alison, Kakkis, Emil, Bedrosian, Camille L, and Mozaffar, Tahseen

Subjects
Biomedical and Clinical Sciences, Neurosciences, Brain Disorders, Clinical Research, Clinical Trials and Supportive Activities, Adult, Bulgaria, Distal Myopathies, Female, Humans, Lower Extremity, Male, Middle Aged, Muscle Strength, Muscle Weakness, Muscle, Skeletal, Prospective Studies, Young Adult, Myopathies, muscular diseases, muscle weakness, N-acetylneuraminic acid
Abstract

BackgroundGNE myopathy is a rare, autosomal recessive, muscle disease caused by mutations in GNE and is characterized by rimmed vacuoles on muscle biopsy and progressive distal to proximal muscle weakness.ObjectiveInvestigate the clinical presentation and progression of GNE myopathy.MethodsThe GNE Myopathy Disease Monitoring Program was an international, prospective, observational study in subjects with GNE myopathy. Muscle strength was assessed with hand-held dynamometry (HHD), with upper extremity (UE) and lower extremity (LE) composite scores reflecting upper and lower extremity muscle groups, respectively. The GNE myopathy-Functional Activity Scale (GNEM-FAS) was used to further assess impairment in mobility, upper extremity function, and self-care.ResultsEighty-seven of 101 enrolled subjects completed the trial until study closure by the sponsor; 60 completed 36 months. Mean (SD) HHD UE composite score decreased from 34.3 kg (32.0) at baseline to 29.4 kg (32.6) kg at month 36 (LS mean change [95%CI]: -3.8 kg [-5.9, -1.7]; P = 0.0005). Mean (SD) HHD LE composite score decreased from 32.0 kg (34.1) at baseline to 25.5 kg (31.2) at month 36 (LS mean change [95%CI]: -4.9 [-7.7, -2.2]; P = 0.0005). GNEM-FAS scores were more severe at baseline in subjects who walked

Published
2021

2. A phase 3 randomized study evaluating sialic acid extended-release for GNE myopathy

Author

Lochmüller, Hanns, Behin, Anthony, Caraco, Yoseph, Lau, Heather, Mirabella, Massimiliano, Tournev, Ivailo, Tarnopolsky, Mark, Pogoryelova, Oksana, Woods, Catherine, Lai, Alexander, Shah, Jinay, Koutsoukos, Tony, Skrinar, Alison, Mansbach, Hank, Kakkis, Emil, and Mozaffar, Tahseen

Subjects
Clinical Research, Clinical Trials and Supportive Activities, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Adult, Delayed-Action Preparations, Distal Myopathies, Double-Blind Method, Female, Humans, Male, Middle Aged, Muscle Strength, Muscle, Skeletal, N-Acetylneuraminic Acid, Treatment Outcome, Young Adult, Clinical Sciences, Neurosciences, Cognitive Sciences, Neurology & Neurosurgery
Abstract

ObjectiveTo investigate the efficacy and safety of aceneuramic acid extended-release (Ace-ER), a treatment intended to replace deficient sialic acid, in patients with GNE myopathy.MethodsUX001-CL301 was a phase 3, double-blind, placebo-controlled, randomized, international study evaluating the efficacy and safety of Ace-ER in patients with GNE myopathy. Participants who could walk ≥200 meters in a 6-minute walk test at screening were randomized 1:1, and stratified by sex, to receive Ace-ER 6 g/d or placebo for 48 weeks and assessed every 8 weeks. The primary endpoint was change in muscle strength over 48 weeks measured by upper extremity composite (UEC) score. Key secondary endpoints included change in lower extremity composite (LEC) score, knee extensor strength, and GNE myopathy-Functional Activity Scale (GNEM-FAS) mobility domain score. Safety assessments included adverse events (AEs), vital signs, and clinical laboratory results.ResultsEighty-nine patients were randomized (Ace-ER n = 45; placebo n = 44). Change from baseline to week 48 for UEC score between treatments did not differ (least square mean [LSM] Ace-ER -2.25 kg vs placebo -2.99 kg; LSM difference confidence interval [CI] 0.74 [-1.61 to 3.09]; p = 0.5387). At week 48, there was no significant difference between treatments for the change in key secondary endpoints: LEC LSM difference (CI) -1.49 (-5.83 to 2.86); knee extension strength -0.40 (-2.38 to 1.58); and GNEM-FAS mobility domain score -0.72 (-2.01 to 0.57). Gastrointestinal events were the most common AEs.ConclusionsAce-ER was not superior to placebo in improving muscle strength and function in patients with GNE myopathy.Classification of evidenceThis study provides Class I evidence that for patients with GNE myopathy, Ace-ER does not improve muscle strength compared to placebo.

Published
2019

4. Characterization of Strength and Function in Ambulatory Adults With GNE Myopathy.

Author

Argov, Zohar, Bronstein, Faye, Esposito, Alicia, Feinsod-Meiri, Yael, Florence, Julaine, Fowler, Eileen, Greenberg, Marcia, Malkus, Elizabeth, Rebibo, Odelia, Siener, Catherine, Caraco, Yoseph, Kolodny, Edwin, Lau, Heather, Pestronk, Alan, Shieh, Perry, Skrinar, Alison, and Mayhew, Jill

Subjects
Adolescent, Adult, Aged, Female, Humans, Lower Extremity, Male, Middle Aged, Motor Activity, Muscle Strength, Muscle Weakness, Muscle, Skeletal, Myositis, Inclusion Body, N-Acetylneuraminic Acid, Young Adult
Abstract

OBJECTIVE: To characterize the pattern and extent of muscle weakness and impact on physical functioning in adults with GNEM. METHODS: Strength and function were assessed in GNEM subjects (n = 47) using hand-held dynamometry, manual muscle testing, upper and lower extremity functional capacity tests, and the GNEM-Functional Activity Scale (GNEM-FAS). RESULTS: Profound upper and lower muscle weakness was measured using hand-held dynamometry in a characteristic pattern, previously described. Functional tests and clinician-reported outcomes demonstrated the consequence of muscle weakness on physical functioning. CONCLUSIONS: The characteristic pattern of upper and lower muscle weakness associated with GNEM and the resulting functional limitations can be reliably measured using these clinical outcome assessments of muscle strength and function.

Published
2017

5. Patient-Reported Outcomes from a Randomized, Active-Controlled, Open-Label, Phase 3 Trial of Burosumab Versus Conventional Therapy in Children with X-Linked Hypophosphatemia

Author

Padidela, Raja, Whyte, Michael P., Glorieux, Francis H., Munns, Craig F., Ward, Leanne M., Nilsson, Ola, Portale, Anthony A., Simmons, Jill H., Namba, Noriyuki, Cheong, Hae Il, Pitukcheewanont, Pisit, Sochett, Etienne, Högler, Wolfgang, Muroya, Koji, Tanaka, Hiroyuki, Gottesman, Gary S., Biggin, Andrew, Perwad, Farzana, Williams, Angela, Nixon, Annabel, Sun, Wei, Chen, Angel, Skrinar, Alison, and Imel, Erik A.

Published
2021
Full Text
View/download PDF

9. Effect of Burosumab Compared With Conventional Therapy on Younger vs Older Children With X-linked Hypophosphatemia

Author

Ward, Leanne M., Glorieux, Francis H., Whyte, Michael P., Munns, Craig F., Portale, Anthony A., Högler, Wolfgang, Simmons, Jill H., Gottesman, Gary S., Padidela, Raja, Namba, Noriyuki, Cheong, Hae Il, Nilsson, Ola, Mao, Meng, Chen, Angel, Skrinar, Alison, Roberts, Mary Scott, Imel, Erik A., Ward, Leanne M., Glorieux, Francis H., Whyte, Michael P., Munns, Craig F., Portale, Anthony A., Högler, Wolfgang, Simmons, Jill H., Gottesman, Gary S., Padidela, Raja, Namba, Noriyuki, Cheong, Hae Il, Nilsson, Ola, Mao, Meng, Chen, Angel, Skrinar, Alison, Roberts, Mary Scott, and Imel, Erik A.

Abstract

CONTEXT: Younger age at treatment-onset with conventional therapy (Pi/D) is associated with improved growth and skeletal outcomes in children with X-linked hypophosphatemia (XLH). The impact of age on burosumab efficacy and safety in XLH is unknown. OBJECTIVE: Explore the efficacy and safety of burosumab versus Pi/D in younger (<5 years) and older (5 to 12 years) children with XLH. DESIGN: Post-hoc analysis of 64-week, open-label, randomized controlled study. SETTING: Sixteen academic centers. PATIENTS OR OTHER PARTICIPANTS: Sixty-one children 1-12 years of age with XLH (younger, n=26; older, n=35). INTERVENTIONS: Children received burosumab starting at 0.8 mg/kg every 2 weeks (younger, n=14; older, n=15) or continued Pi/D individually titrated per recommended guidelines (younger, n=12; older, n=20). MAIN OUTCOME MEASURE: Least squares means difference (LSMD) in Radiographic Global Impression of Change (RGI-C) rickets total score from baseline to week 64. RESULTS: The LSMD in outcomes through 64 weeks on burosumab versus conventional therapy by age group were as follows: RGI-C rickets total score (younger, +0.90; older, +1.07), total rickets severity score (younger, -0.86; older, -1.44), RGI-C lower limb deformity score (younger, +1.02; older, +0.91), recumbent length or standing height Z-score (younger, +0.20; older, +0.09), and serum alkaline phosphatase (younger, -31.15% of upper normal limit [ULN]; older, -52.11% of ULN). On burosumab, dental abscesses were not reported in younger children but were in 53% of older children. CONCLUSIONS: Burosumab appears to improve outcomes in both younger and older children with XLH, including rickets, lower limb deformities, growth, and alkaline phosphatase, compared with Pi/D., Funding agencies:Ultragenyx Pharmaceutical Inc.Kyowa Kirin International plcUniversity of Ottawa Clinical Research Chair Program

Published
2022
Full Text
View/download PDF

10. Patient-reported outcomes from a randomized open-label phase 3 trial comparing burosumab versus conventional therapy in children with X-linked hypophosphatemia : results from the 24-week treatment extension period

Author

Padidela, Raja, Whyte, Michael P., Glorieux, Francis H., Munns, Craig F., Ward, Leanne M., Nilsson, Ola, Portale, Anthony A., Simmons, Jill H., Namba, Noriyuki, Cheong, Hae Il, Pitukcheewanont, Pisit, Sochett, Etienne, Högler, Wolfgang, Muroya, Koji, Gottesman, Gary S., Biggin, Andrew, Perwad, Farzana, Williams, Angela, Nixon, Annabel, Sun, Wei, Chen, Angel, Skrinar, Alison, Imel, Erik A., Padidela, Raja, Whyte, Michael P., Glorieux, Francis H., Munns, Craig F., Ward, Leanne M., Nilsson, Ola, Portale, Anthony A., Simmons, Jill H., Namba, Noriyuki, Cheong, Hae Il, Pitukcheewanont, Pisit, Sochett, Etienne, Högler, Wolfgang, Muroya, Koji, Gottesman, Gary S., Biggin, Andrew, Perwad, Farzana, Williams, Angela, Nixon, Annabel, Sun, Wei, Chen, Angel, Skrinar, Alison, and Imel, Erik A.

Abstract

In a randomized open-label phase 3 trial in 62 children (1–12 years) with X-linked hypophosphatemia (XLH) (NCT 02915705), switching from conventional therapy (oral phosphate plus active vitamin D) to burosumab, a monoclonal antibody targeting fibroblast growth factor 23, significantly improved serum phosphate concentration, rickets, lower-extremity deformities, growth, mobility, and patient-reported outcomes (PROs) at 64 weeks. Children in Europe, USA, Canada, and Australia who completed 64 weeks’ treatment could continue to receive burosumab in the extension period (burosumab continuation group) or cross over from conventional therapy to burosumab (crossover group) to 124 weeks. A Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaire was used in children aged ≥5 years to measure Pain Interference, Physical Function Mobility, and Fatigue; health-related quality of life was measured using the SF-10 Health Survey for Children (n=35). Here, we describe changes in PROs from baseline to weeks 64 and 88, and report whether the 3-point minimal important difference (MID) was reached for PROMIS domains (Thissen et al., 2016; PMID 26118768). The mean change from baseline exceeded the MID for Pain Interference at weeks 64 and 88 and for Fatigue at week 64 in the burosumab continuation group, and for Pain Interference and Fatigue at week 88 in the crossover group. Similar improvements in SF-10 Physical Health were seen baseline to week 64 in the burosumab continuation group, and week 64 to 88 in the cross-over group. SF-10 Psychosocial Health changed little in either group at the two timepoints. Treatment with burosumab improved Pain Interference and Fatigue beyond the MID in children with XLH who switched from conventional therapy to receive 24 weeks of burosumab. Improvements were also maintained in children who received an additional 24 weeks’ burosumab treatment.

Published
2022

11. Effect of Burosumab Compared With Conventional Therapy on Younger vs Older Children With X-linked Hypophosphatemia

Author

Ward, Leanne M, primary, Glorieux, Francis H, additional, Whyte, Michael P, additional, Munns, Craig F, additional, Portale, Anthony A, additional, Högler, Wolfgang, additional, Simmons, Jill H, additional, Gottesman, Gary S, additional, Padidela, Raja, additional, Namba, Noriyuki, additional, Cheong, Hae Il, additional, Nilsson, Ola, additional, Mao, Meng, additional, Chen, Angel, additional, Skrinar, Alison, additional, Roberts, Mary Scott, additional, and Imel, Erik A, additional

Published
2022
Full Text
View/download PDF

13. Sustained Efficacy and Safety of Burosumab, a Monoclonal Antibody to FGF23, in Children With X-Linked Hypophosphatemia

Author

Linglart, Agnès, primary, Imel, Erik A, additional, Whyte, Michael P, additional, Portale, Anthony A, additional, Högler, Wolfgang, additional, Boot, Annemieke M, additional, Padidela, Raja, additional, van’t Hoff, William, additional, Gottesman, Gary S, additional, Chen, Angel, additional, Skrinar, Alison, additional, Scott Roberts, Mary, additional, and Carpenter, Thomas O, additional

Published
2021
Full Text
View/download PDF

16. Phenotypic stratification and genotype–phenotype correlation in a heterogeneous, international cohort of GNE myopathy patients: First report from the GNE myopathy Disease Monitoring Program, registry portion

Author

Pogoryelova, Oksana, Cammish, Phillip, Mansbach, Hank, Argov, Zohar, Nishino, Ichizo, Skrinar, Alison, Chan, Yiumo, Nafissi, Shahriar, Shamshiri, Hosein, Kakkis, Emil, and Lochmüller, Hanns

Subjects
Adult, Male, Genotype-phenotype correlation, Internationality, Epidemiology, Distal myopathy, Hereditary inclusion body myopathy, Middle Aged, Severity of Illness Index, Article, GNE myopathy, Cohort Studies, Distal Myopathies, Young Adult, Phenotype, Rare neuromuscular disorders, Multienzyme Complexes, Disease Progression, Humans, Female, Registries, Genetic Association Studies, Aged
Abstract

Highlights • Patient registry is a valuable tool in international GNE myopathy research. • The registry expands the knowledge of GNE myopathy genetics and epidemiology. • The registry allows monitoring of the disease progression and discovering diversity. • The data suggest possible genotype–phenotype correlation in GNE myopathy., GNE myopathy is a rare distal myopathy, caused by mutations in the GNE gene, affecting sialic acid synthesis. Clinical presentation varies from asymptomatic early stage patients to severely debilitating forms. This first report describes clinical presentations and severity of the disease, using data of 150 patients collected via the on-line, patient-reported registry component of the GNE Myopathy Disease Monitoring Program (GNEM-DMP). Disease progression was prospectively analysed, over a 2-year period, using the GNE myopathy functional activity scale (GNEM-FAS). The average annual rates of decline in function were estimated at −9.6% and −3.2% in ambulant and non-ambulant patients respectively. 4.3% of participants became non-ambulant within one year. The mean time from onset to required use of a wheelchair was 11.9 years. Mean delay of genetic diagnosis from symptom onset was 5.2 years. Mutation specific analysis demonstrated genotype–phenotype relationships; i.e. p.Ala662Val may be associated with a more severe phenotype, compared to p.Val727Met. Patients with compound heterozygous mutation in epimerase and kinase domain appeared to have a more severe phenotype compared to patients with both mutations located within one domain. Acknowledging the limitations of the study, these findings suggest that the severity of the GNE mutations affects disease severity. The GNEM-DMP is a useful data collection tool, prospectively measuring the progression of GNE myopathy, which could play an important role in translational and clinical research and further understanding of genotype–phenotype correlations.

Published
2018

18. Sustained Efficacy and Safety of Burosumab, a Monoclonal Antibody to FGF23, in Children With X-Linked Hypophosphatemia.

Author

Linglart, Agnès, Imel, Erik A., Whyte, Michael P., Portale, Anthony A., Högler, Wolfgang, Boot, Annemieke M., Padidela, Raja, van't Hoff, William, Gottesman, Gary S., Chen, Angel, Skrinar, Alison, Roberts, Mary Scott, and Carpenter, Thomas O.

Subjects
MONOCLONAL antibodies, HYPOPHOSPHATEMIA
Abstract

Purpose: In X-linked hypophosphatemia (XLH), excess fibroblast growth factor-23 causes hypophosphatemia and low calcitriol, leading to musculoskeletal disease with clinical consequences. XLH treatment options include conventional oral phosphate with active vitamin D, or monotherapy with burosumab, a monoclonal antibody approved to treat children and adults with XLH. We have previously reported outcomes up to 64 weeks, and here we report safety and efficacy follow-up results up to 160 weeks from an open-label, multicenter, randomized, dose-finding trial of burosumab for 5- to 12-yearold children with XLH. Methods: After 1 week of conventional therapy washout, patients were randomized 1:1 to burosumab every 2 weeks (Q2W) or every 4 weeks (Q4W) for 64 weeks, with dosing titrated based on fasting serum phosphorus levels between baseline and week 16. From week 66 to week 160, all patients received Q2W burosumab. Results: Twenty-six children were randomized initially into each Q2W and Q4W group and all completed treatment to week 160. In 41 children with open distal femoral and proximal tibial growth plates (from both treatment groups), total Rickets Severity Score significantly decreased by 0.9 ± 0.1 (least squares mean ± SE; P < 0.0001) from baseline to week 160. Fasting serum phosphorus increases were sustained by burosumab therapy throughout the study, with an overall population mean (SD) of 3.35 (0.39) mg/dL, within the pediatric normal range (3.2-6.1 mg/dL) at week 160 (mean change from baseline P < 0.0001). Most adverse events were mild to moderate in severity. Main conclusions: In children with XLH, burosumab administration for 160 weeks improved phosphate homeostasis and rickets and was well-tolerated. Long-term safety was consistent with the reported safety profile of burosumab. [ABSTRACT FROM AUTHOR]

Published
2022
Full Text
View/download PDF

19. Enzyme-Replacement Therapy in Life-Threatening Hypophosphatasia

Author

Whyte, Michael P., Greenberg, Cheryl R., Salman, Nada J., Bober, Michael B., McAlister, William H., Wenkert, Deborah, Van Sickle, Bradley J., Simmons, Jill H., Edgar, Terence S., Bauer, Martin L., Hamdan, Mohamed A., Bishop, Nick, Lutz, Richard E., McGinn, Mairead, Craig, Stanley, Moore, Jean N., Taylor, John W., Cleveland, Robert H., Cranley, William R., Lim, Ruth, Thacher, Tom D., Mayhew, Jill E., Downs, Matthew, Millán, José Luis, Skrinar, Alison M., Crine, Philippe, and Landy, Hal

Published
2012

20. Long-term safety in adults with X-linked Hypophosphatemia (XLH) treated with Burosumab, a fully human monoclonal antibody against FGF23: Final results of a phase 3 trial

Author

Kamenický, Peter, primary, Portale, Anthony A., additional, Carpenter, Tom, additional, Briot, Karine, additional, Imel, Erik A., additional, Weber, Thomas, additional, Pitukcheewanont, Pisit, additional, Cheong, Hae Il, additional, de Beur, Suzanne Jan, additional, Imanishi, Yasuo, additional, Ito, Nobuaki, additional, Lachmann, Robin, additional, Tanaka, Hiroyuki, additional, Perwad, Farzana, additional, Zhang, Lin, additional, Skrinar, Alison, additional, Rees, Linda, additional, and Insogna, Karl L., additional

Published
2020
Full Text
View/download PDF

22. OR29-01 Long-Term Safety in Adults with X-Linked Hypophosphatemia (XLH) Treated with Burosumab, a Fully Human Monoclonal Antibody Against FGF23: Final Results of a Phase 3 Trial

Author

Perwad, Farzana, primary, Portale, Anthony A, primary, Carpenter, Thomas O, primary, Briot, Karine, primary, Imel, Erik Allen, primary, Kamenicky, Peter, primary, Weber, Thomas Joseph, primary, Pitukcheewanont, Pisit, primary, Cheong, Hae Il, primary, De Beur, Suzanne Marie Jan, primary, Imanishi, Yasuo, primary, Ito, Nobuaki, primary, Lachmann, Robin, primary, Tanaka, Hiroyuki, primary, Zhang, Lin, primary, Skrinar, Alison, primary, Rees, Linda, primary, and Insogna, Karl Leonard, primary

Published
2020
Full Text
View/download PDF

23. A Randomized Study of Alglucosidase Alfa in Late-Onset Pompeʼs Disease

Author

van der Ploeg, Ans T., Clemens, Paula R., Corzo, Deyanira, Escolar, Diana M., Florence, Julaine, Groeneveld, Geert Jan, Herson, Serge, Kishnani, Priya S., Laforet, Pascal, Lake, Stephen L., Lange, Dale J., Leshner, Robert T., Mayhew, Jill E., Morgan, Claire, Nozaki, Kenkichi, Park, Dorothy J., Pestronk, Alan, Rosenbloom, Barry, Skrinar, Alison, van Capelle, Carine I., van der Beek, Nadine A., Wasserstein, Melissa, and Zivkovic, Sasa A.

Published
2010
Full Text
View/download PDF

24. Burosumab versus conventional therapy in children with X-linked hypophosphataemia : a randomised, active-controlled, open-label, phase 3 trial

Author

Imel, Erik A., Glorieux, Francis H., Whyte, Michael P., Munns, Craig F., Ward, Leanne M., Nilsson, Ola, Simmons, Jill H., Padidela, Raja, Namba, Noriyuki, Cheong, Hae Il, Pitukcheewanont, Pisit, Sochett, Etienne, Högler, Wolfgang, Muroya, Koji, Tanaka, Hiroyuki, Gottesman, Gary S., Biggin, Andrew, Perwad, Farzana, Mao, Meng, Chen, Chao-Yin, Skrinar, Alison, San Martin, Javier, Portale, Anthony A., Imel, Erik A., Glorieux, Francis H., Whyte, Michael P., Munns, Craig F., Ward, Leanne M., Nilsson, Ola, Simmons, Jill H., Padidela, Raja, Namba, Noriyuki, Cheong, Hae Il, Pitukcheewanont, Pisit, Sochett, Etienne, Högler, Wolfgang, Muroya, Koji, Tanaka, Hiroyuki, Gottesman, Gary S., Biggin, Andrew, Perwad, Farzana, Mao, Meng, Chen, Chao-Yin, Skrinar, Alison, San Martin, Javier, and Portale, Anthony A.

Abstract

Background: X-linked hypophosphataemia in children is characterised by elevated serum concentrations of fibroblast growth factor 23 (FGF23), hypophosphataemia, rickets, lower extremity bowing, and growth impairment. We compared the efficacy and safety of continuing conventional therapy, consisting of oral phosphate and active vitamin D, versus switching to burosumab, a fully human monoclonal antibody against FGF23, in paediatric X-linked hypophosphataemia. Methods: In this randomised, active-controlled, open-label, phase 3 trial at 16 clinical sites, we enrolled children with X-linked hypophosphataemia aged 1-12 years. Key eligibility criteria were a total Thacher rickets severity score of at least 2.0, fasting serum phosphorus lower than 0.97 mmol/L (3.0 mg/dL), confirmed PHEX (phosphate-regulating endopep-tidase homolog, X-linked) mutation or variant of unknown significance in the patient or a family member with appropriate X-linked dominant inheritance, and receipt of conventional therapy for at least 6 consecutive months for children younger than 3 years or at least 12 consecutive months for children older than 3 years. Eligible patients were randomly assigned (1: 1) to receive either subcutaneous burosumab starting at 0.8 mg/kg every 2 weeks (burosumab group) or conventional therapy prescribed by investigators (conventional therapy group). Both interventions lasted 64 weeks. The primary endpoint was change in rickets severity at week 40, assessed by the Radiographic Global Impression of Change global score. All patients who received at least one dose of treatment were included in the primary and safety analyses. The trial is registered with ClinicalTrials.gov, number NCT02915705. Findings: Recruitment took place between Aug 3, 2016, and May 8, 2017. Of 122 patients assessed, 61 were enrolled. Of these, 32 (18 girls, 14 boys) were randomly assigned to continue receiving conventional therapy and 29 (16 girls, 13 boys) to receive burosumab. For the primary endpoin, Funding Agencies:Ultragenyx Pharmaceutical Kyowa Kirin International

Published
2019
Full Text
View/download PDF

25. A phase 3 randomized study evaluating sialic acid extended-release for GNE myopathy

Author

Lochmüller, Hann, Behin, Anthony, Caraco, Yoseph, Lau, Heather, Mirabella, Massimiliano, Tournev, Ivailo, Tarnopolsky, Mark, Pogoryelova, Oksana, Woods, Catherine, Lai, Alexander, Shah, Jinay, Koutsoukos, Tony, Skrinar, Alison, Mansbach, Hank, Kakkis, Emil, Mozaffar, Tahseen, Mirabella, Massimiliano (ORCID:0000-0002-7783-114X), Lochmüller, Hann, Behin, Anthony, Caraco, Yoseph, Lau, Heather, Mirabella, Massimiliano, Tournev, Ivailo, Tarnopolsky, Mark, Pogoryelova, Oksana, Woods, Catherine, Lai, Alexander, Shah, Jinay, Koutsoukos, Tony, Skrinar, Alison, Mansbach, Hank, Kakkis, Emil, Mozaffar, Tahseen, and Mirabella, Massimiliano (ORCID:0000-0002-7783-114X)

Abstract

OBJECTIVE: To investigate the efficacy and safety of aceneuramic acid extended-release (Ace-ER), a treatment intended to replace deficient sialic acid, in patients with GNE myopathy. METHODS: UX001-CL301 was a phase 3, double-blind, placebo-controlled, randomized, international study evaluating the efficacy and safety of Ace-ER in patients with GNE myopathy. Participants who could walk ≥200 meters in a 6-minute walk test at screening were randomized 1:1, and stratified by sex, to receive Ace-ER 6 g/d or placebo for 48 weeks and assessed every 8 weeks. The primary endpoint was change in muscle strength over 48 weeks measured by upper extremity composite (UEC) score. Key secondary endpoints included change in lower extremity composite (LEC) score, knee extensor strength, and GNE myopathy-Functional Activity Scale (GNEM-FAS) mobility domain score. Safety assessments included adverse events (AEs), vital signs, and clinical laboratory results. RESULTS: Eighty-nine patients were randomized (Ace-ER n = 45; placebo n = 44). Change from baseline to week 48 for UEC score between treatments did not differ (least square mean [LSM] Ace-ER -2.25 kg vs placebo -2.99 kg; LSM difference confidence interval [CI] 0.74 [-1.61 to 3.09]; p = 0.5387). At week 48, there was no significant difference between treatments for the change in key secondary endpoints: LEC LSM difference (CI) -1.49 (-5.83 to 2.86); knee extension strength -0.40 (-2.38 to 1.58); and GNEM-FAS mobility domain score -0.72 (-2.01 to 0.57). Gastrointestinal events were the most common AEs. CONCLUSIONS: Ace-ER was not superior to placebo in improving muscle strength and function in patients with GNE myopathy. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for patients with GNE myopathy, Ace-ER does not improve muscle strength compared to placebo.

Published
2019

26. Burosumab resulted in greater improvement in clinical outcomes than continuation with conventional therapy in younger (1-4 years-old) and older (5-12 years-old) children with X-linked hypophosphatemia

Author

Ward, Leanne, primary, Imel, Erik, additional, Whyte, Michael, additional, Munns, Craig, additional, Portale, Anthony, additional, Hogler, Wolfgang, additional, Simmons, Jill, additional, Padidela, Raja, additional, Namba, Noriyuki, additional, Cheong, Hae, additional, Nilsson, Ola, additional, Mao, Meng, additional, Skrinar, Alison, additional, Chen, Chao-Yin, additional, Martin, Javier San, additional, and Glorieux, Francis, additional

Published
2019
Full Text
View/download PDF

27. Sustained efficacy and safety of burosumab, a fully human anti-FGF23 monoclonal antibody, in children and early adolescents with X-linked hypophosphatemia

Author

Hogler, Wolfgang, primary, Carpenter, Thomas, additional, Imel, Erik, additional, Portale, Anthony, additional, Boot, Annemieke, additional, Linglart, Agnes, additional, Padidela, Raja, additional, Hoff, William van't, additional, Mao, Meng, additional, Skrinar, Alison, additional, Martin, Javier San, additional, and Whyte, Michael, additional

Published
2019
Full Text
View/download PDF

29. Burosumab versus conventional therapy in children with X-linked hypophosphataemia: a randomised, active-controlled, open-label, phase 3 trial

Author

Imel, Erik A, primary, Glorieux, Francis H, additional, Whyte, Michael P, additional, Munns, Craig F, additional, Ward, Leanne M, additional, Nilsson, Ola, additional, Simmons, Jill H, additional, Padidela, Raja, additional, Namba, Noriyuki, additional, Cheong, Hae Il, additional, Pitukcheewanont, Pisit, additional, Sochett, Etienne, additional, Högler, Wolfgang, additional, Muroya, Koji, additional, Tanaka, Hiroyuki, additional, Gottesman, Gary S, additional, Biggin, Andrew, additional, Perwad, Farzana, additional, Mao, Meng, additional, Chen, Chao-Yin, additional, Skrinar, Alison, additional, San Martin, Javier, additional, and Portale, Anthony A, additional

Published
2019
Full Text
View/download PDF

31. OR13-2 Burosumab Resulted in Greater Improvement in Rickets Than Conventional Therapy in Children with X-Linked Hypophosphatemia (XLH)

Author

Imel, Erik, primary, Whyte, Michael, additional, Munns, Craig, additional, Portale, Anthony, additional, Ward, Leanne, additional, Nilsson, Ola, additional, Simmons, Jill, additional, Padidela, Raja, additional, Namba, Noriyuki, additional, Cheong, Hae Il, additional, Mao, Meng, additional, Chen, Chao-Yin, additional, Skrinar, Alison, additional, San Martin, Javier, additional, and Glorieux, Francis, additional

Published
2019
Full Text
View/download PDF

32. Burosumab Improved Rickets, Phosphate Metabolism, and Clinical Outcomes Compared to Conventional Therapy in Children with X-Linked Hypophosphatemia (XLH) - A Randomized Controlled Phase 3 Study

Author

Nilsson, Ola, Whyte, Michael P., Imel, Erik A., Munns, Craig, Portale, Anthony A., Ward, Leanne, Simmons, Jill H., Padidela, Raja, Namba, Noriyuki, Cheong, Hae Il, Mao, Meng, Skrinar, Alison, Chen, Chao-Yin, Martin, Javier San, Glorieux, Francis, Nilsson, Ola, Whyte, Michael P., Imel, Erik A., Munns, Craig, Portale, Anthony A., Ward, Leanne, Simmons, Jill H., Padidela, Raja, Namba, Noriyuki, Cheong, Hae Il, Mao, Meng, Skrinar, Alison, Chen, Chao-Yin, Martin, Javier San, and Glorieux, Francis

Abstract

In children with XLH, high circulating levels of FGF23 cause hypophosphatemia with consequent rickets, skeletal deformities, and growth impairment. Conventional therapy consists of multiple daily doses of oral phosphate and active vitamin D (Pi/D). Burosumab is a fully human monoclonal antibody against FGF23 indicated for the treatment of XLH. In the active-control study CL301 (NCT02915705), 61 children with XLH (1-12 years old) were randomized (1:1) to receive subcutaneous burosumab starting at 0.8 mg/kg every 2 weeks (Q2W) or Pi/D as prescribed by investigators. Eligibility criteria included a Total Rickets Severity Score (RSS) ≥2.0 and prior receipt of Pi/D. The primary endpoint was healing of rickets at Week 40 assessed by radiologists blinded to treatment using the Radiographic Global Impression of Change (RGI-C). At Week 40, burosumab significantly improved rickets compared with Pi/D (RGI-C global score least squares [LS] mean ± SE: +1.92 ± 0.11 vs +0.77 ± 0.11; p<0.0001). More subjects in the burosumab group had substantial healing (RGI-C ≥+2.0) at Week 40, compared with the Pi/D group (21/29, 72% vs 2/32, 6%; odds ratio of 39.1, p<0.0001). Additional evidence for improvement of rickets included decreased Total RSS (LS mean ± SE change, burosumab vs Pi/D: -2.04 ± 0.145 vs -0.71 ± 0.138; p<0.0001), decreased alkaline phosphatase (-131 ± 13 vs -35 ± 19; p<0.0001), and improved RGI-C lower limb deformity score (+0.62 ± 0.12 vs +0.21 ± 0.12; p=0.020). At Week 40, increases in serum phosphorous (p<0.0001) and TmP/GFR (p<0.0001) were significantly greater with burosumab compared with Pi/D. Standing height Z-score increased in both treatment groups from baseline to Week 40 with an LS mean change of +0.15 (95% CI: 0.05, 0.25) for burosumab and +0.08 (-0.02, 0.19) for Pi/D. Percent predicted distance walked in six minutes increased with burosumab (Baseline to Week 40: 62% to 72%) and was unchanged with Pi/D (76% to 75%). Pre-defined adverse events (A

Published
2018

33. Growth Curves for Children with X-linked Hypophosphatemia.

Author

Meng Mao, Carpenter, Thomas O., Whyte, Michael P., Skrinar, Alison, Chao-Yin Chen, Martin, Javier San, Rogol, Alan D., Mao, Meng, Chen, Chao-Yin, and San Martin, Javier

Subjects
GROWTH of children, HYPOPHOSPHATEMIA, CALCITRIOL, PITUITARY dwarfism, METABOLIC bone disorders, FIBROBLAST growth factors, CLINICAL trial registries, STATURE, X-linked genetic disorders, CLINICAL trials, CHILD development, WEIGHTS & measures, RETROSPECTIVE studies, VITAMIN D, TREATMENT effectiveness, PHOSPHATES
Abstract

Context: We characterized linear growth in infants and children with X-linked hypophosphatemia (XLH).Objective: Provide linear growth curves for children with XLH from birth to early adolescence.Design: Data from 4 prior studies of XLH were pooled to construct growth curves. UX023-CL002 was an observational, retrospective chart review. Pretreatment data were collected from 3 interventional trials: two phase 2 trials (UX023-CL201, UX023-CL205) and a phase 3 trial (UX023-CL301).Setting: Medical centers with expertise in treating XLH.Patients: Children with XLH, 1-14 years of age.Intervention: None.Main Outcome Measure: Height-for-age linear growth curves, including values for the 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles for children with XLH compared to population norms.Results: A total of 228 patients (132 girls, 96 boys) with 2381 height measurements were included. Nearly all subjects (> 99%) reported prior management with supplementation therapy. Compared to the Center for Disease Control and Prevention growth curves, boys at age 3 months, 6 months, 9 months, 1 year, and 2 years had median height percentiles of 46%, 37%, 26%, 18%, and 5%, respectively; for girls the median height percentiles were 52%, 37%, 25%, 18%, and 7%, respectively. Annual growth in children with XLH fell below that of healthy children near 1 year of age and progressively declined during early childhood, with all median height percentiles < 8% between 2 and 12 years old.Conclusion: Children with XLH show decreased height gain by 1 year of age and remain below population norms thereafter. These data will help evaluate therapeutic interventions on linear growth for pediatric XLH. [ABSTRACT FROM AUTHOR]

Published
2020
Full Text
View/download PDF

34. Burosumab Therapy in Children with X-Linked Hypophosphatemia

Author

Carpenter, Thomas O., primary, Whyte, Michael P., additional, Imel, Erik A., additional, Boot, Annemieke M., additional, Högler, Wolfgang, additional, Linglart, Agnès, additional, Padidela, Raja, additional, van’t Hoff, William, additional, Mao, Meng, additional, Chen, Chao-Yin, additional, Skrinar, Alison, additional, Kakkis, Emil, additional, San Martin, Javier, additional, and Portale, Anthony A., additional

Published
2018
Full Text
View/download PDF

36. Abstract #525 Burosumab for X-Linked Hypophosphatemia (XLH): Results from Two Pediatric Phase 2 Trials

Author

Portale, Anthony, primary, Imel, Erik, additional, Whyte, Michael, additional, Boot, Annemieke, additional, Högler, Wolfgang, additional, Linglart, Agnès, additional, Padidela, Raja, additional, vant Hoff, William, additional, Gottesman, Gary, additional, Mao, Meng, additional, Skrinar, Alison, additional, Martin, Javier San, additional, and Carpenter, Thomas, additional

Published
2018
Full Text
View/download PDF

37. Effects of KRN23, a fully human anti-FGF23 monoclonal antibody, on functional outcomes in children with X-linked hypophosphatemia (XLH): results from a randomized, open-label Phase 2 study

Author

Imel, Erik, primary, Carpenter, Thomas, additional, Linglart, Agnes, additional, Boot, Annemieke, additional, Hogler, Wolfgang, additional, Padidela, Raja, additional, van't, Hoff William, additional, Portale, Anthony, additional, Mao, Meng, additional, Skrinar, Alison, additional, San, Martin Javier, additional, and Whyte, Michael P, additional

Published
2017
Full Text
View/download PDF

39. A randomized, open-label Phase 2 study of KRN23, an investigational fully human Anti-FGF23 monoclonal antibody, in children with X-linked Hypophosphatemia (XLH)

Author

Hogler, Wolfgang, primary, Portale, Anthony, additional, Imel, Erik, additional, Boot, Annemieke, additional, Linglart, Agnes, additional, Padidela, Raja, additional, van't, Hoff William, additional, Whyte, Michael, additional, Mao, Meng, additional, Skrinar, Alison, additional, Martin, Javier San, additional, and Carpenter, Thomas, additional

Published
2017
Full Text
View/download PDF

41. Effect of KRN23, a fully human anti-FGF23 monoclonal antibody, on rickets in children with X-linked hypophosphatemia (XLH): 40-week interim results from a randomized, open-label phase 2 study

Author

Padidela, Raja, primary, van't, Hoff William, additional, Hogler, Wolfgang, additional, Portale, Anthony, additional, Imel, Erik, additional, Boot, Annemieke, additional, Linglart, Agnes, additional, Whyte, Michael, additional, Skrinar, Alison, additional, San, Martin Javier, additional, and Carpenter, Thomas, additional

Published
2016
Full Text
View/download PDF

42. Neurocognitive clinical outcome assessments for inborn errors of metabolism and other rare conditions

Author

Shapiro, Elsa, primary, Bernstein, Jessica, additional, Adams, Heather R., additional, Barbier, Ann J., additional, Buracchio, Teresa, additional, Como, Peter, additional, Delaney, Kathleen A., additional, Eichler, Florian, additional, Goldsmith, Jonathan C., additional, Hogan, Melissa, additional, Kovacs, Sarrit, additional, Mink, Jonathan W., additional, Odenkirchen, Joanne, additional, Parisi, Melissa A., additional, Skrinar, Alison, additional, Waisbren, Susan E., additional, and Mulberg, Andrew E., additional

Published
2016
Full Text
View/download PDF

43. Effect of KRN23, a fully human anti-FGF23 monoclonal antibody, on rickets in children with X-linked hypophosphatemia (XLH): 40-week interim results from a randomized, open-label Phase 2 study

Author

Imel, Erik, primary, Carpenter, Thomas, additional, Boot, Annemieke, additional, Hogler, Wolfgang, additional, Linglart, Agnes, additional, Padidela, Raja, additional, van't, Hoff William, additional, Whyte, Michael, additional, Agarwal, Sunil, additional, Chen, Chao-Yin, additional, Skrinar, Alison, additional, Martin, Javier San, additional, and Portale, Anthony, additional

Published
2016
Full Text
View/download PDF

44. Aceneuramic Acid Extended Release Administration Maintains Upper Limb Muscle Strength in a 48-week Study of Subjects with GNE Myopathy: Results from a Phase 2, Randomized, Controlled Study

Author

Argov, Zohar, primary, Caraco, Yoseph, additional, Lau, Heather, additional, Pestronk, Alan, additional, Shieh, Perry B., additional, Skrinar, Alison, additional, Koutsoukos, Tony, additional, Ahmed, Ruhi, additional, Martinisi, Julia, additional, and Kakkis, Emil, additional

Published
2016
Full Text
View/download PDF

47. Clinical outcomes after long-term treatment with alglucosidase alfa in infants and children with advanced Pompe disease

Author

Nicolino, Marc, primary, Byrne, Barry, additional, Wraith, J. Edmund, additional, Leslie, Nancy, additional, Mandel, Hanna, additional, Freyer, David R., additional, Arnold, Georgianne L., additional, Pivnick, Eniko K., additional, Ottinger, C.J., additional, Robinson, Peter H., additional, Loo, John-Charles A., additional, Smitka, Martin, additional, Jardine, Philip, additional, Tatò, Luciano, additional, Chabrol, Brigitte, additional, McCandless, Shawn, additional, Kimura, Shigemi, additional, Mehta, L., additional, Bali, Deeksha, additional, Skrinar, Alison, additional, Morgan, Claire, additional, Rangachari, Lakshmi, additional, Corzo, Deya, additional, and Kishnani, Priya S., additional

Published
2009
Full Text
View/download PDF

48. Clinical features of late-onset Pompe disease: A prospective cohort study

Author

Wokke, John H.J., primary, Escolar, Diana M., additional, Pestronk, Alan, additional, Jaffe, Kenneth M., additional, Carter, Gregory T., additional, van den Berg, Leonard H., additional, Florence, Julaine M., additional, Mayhew, Jill, additional, Skrinar, Alison, additional, Corzo, Deyanira, additional, and Laforet, Pascal, additional

Published
2008
Full Text
View/download PDF

49. Erratum to “Rapid diagnosis of late-onset Pompe disease by fluorometric assay of α-glucosidase activities in dried blood spots” [Mol. Genet. Metab. 90 (2007) 449–452]

Author

Kallwass, Helmut, primary, Carr, Cortney, additional, Gerrein, Joseph, additional, Titlow, Mariah, additional, Pomponio, Robert, additional, Bali, Deeksha, additional, Dai, Jian, additional, Kishnani, Priya, additional, Skrinar, Alison, additional, Corzo, Deyanira, additional, and Keutzer, Joan, additional

Published
2007
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results