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Record W4391708105 · doi:10.1212/wnl.0000000000208112

Efficacy and Safety of Vamorolone Over 48 Weeks in Boys With Duchenne Muscular Dystrophy

2024· article· en· W4391708105 on OpenAlexaff
Utkarsh J. Dang, Jesse M. Damsker, Michela Guglieri, Paula R. Clemens, Seth J. Perlman, Edward C. Smith, Iain Horrocks, Richard S. Finkel, Jean K. Mah, Nicolas Deconinck, Nathalie Goemans, Jana Haberlová, Volker Straub, L. Mengle-Gaw, Benjamin D. Schwartz, Amy Harper, Perry B. Shieh, Liesbeth De Waele, Diana Castro, Michele Yang, Monique M. Ryan, Craig M. McDonald, M. Tulinius, Richard Webster, Hugh J. McMillan, Nancy L. Kuntz, Vamshi K. Rao, Giovanni Baranello, Stefan Spinty, Anne‐Marie Childs, Annie M. Sbrocchi, Kathryn Selby, Migvis Monduy, Yoram Nevo, Juan J. Vílchez, Andres Nascimento-Osorio, E. Niks, Imelda J. M. de Groot, Marina Katsalouli, John N. van den Anker, Leanne M. Ward, Mika Leinonen, Andrea L. D'Alessandro, Eric P. Hoffman

Bibliographic record

VenueNeurology · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMuscle Physiology and Disorders
Canadian institutionsVeterans Affairs Canada
FundersNational Center for Advancing Translational SciencesDuchenne Research FundNational Institute of Arthritis and Musculoskeletal and Skin DiseasesNational Institutes of HealthNational Institute for Health and Care ResearchParent Project Muscular DystrophyNational Institute of Neurological Disorders and StrokeFoundation to Eradicate DuchenneChildren's TrustEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentEuropean CommissionMuscular Dystrophy Association
KeywordsDuchenne muscular dystrophyMedicinePrednisoneCrossover studyPlaceboAdverse effectSupine positionMuscular dystrophyAmbulatoryRandomized controlled trialInternal medicineAnesthesiaPhysical therapy

Abstract

fetched live from OpenAlex

BACKGROUND AND OBJECTIVES: Vamorolone is a dissociative agonist of the glucocorticoid receptor that has shown similar efficacy and reduced safety concerns in comparison with prednisone in Duchenne muscular dystrophy (DMD). This study was conducted to determine the efficacy and safety of vamorolone over 48 weeks and to study crossover participants (prednisone to vamorolone; placebo to vamorolone). METHODS: A randomized, double-blind, placebo-controlled and prednisone-controlled clinical trial of 2 doses of vamorolone was conducted in participants with DMD, in the ages from 4 years to younger than 7 years at baseline. The interventions were 2 mg/kg/d of vamorolone and 6 mg/kg/d of vamorolone for 48 weeks (period 1: 24 weeks + period 2: 24 weeks) and 0.75 mg/kg/d of prednisone and placebo for the first 24 weeks (before crossover). Efficacy was evaluated through gross motor outcomes and safety through adverse events, growth velocity, body mass index (BMI), and bone turnover biomarkers. This analysis focused on period 2. RESULTS: = 0.67), but less improvement for other motor outcomes. The placebo to vamorolone 6 mg/kg/d group showed rapid improvements after 20 weeks of treatment approaching benefit seen with 48-week 6 mg/kg/d of vamorolone treatment for TTSTAND, time to run/walk 10 m, and NSAA. There was significant improvement in linear growth after crossover in the prednisone to vamorolone 6 mg/kg/d group, and rapid reversal of prednisone-induced decline in bone turnover biomarkers in both crossover groups. There was an increase in BMI after 24 weeks of treatment that then stabilized for both vamorolone groups. DISCUSSION: Improvements of motor outcomes seen with 6 mg/kg/d of vamorolone at 24 weeks of treatment were maintained to 48 weeks of treatment. Vamorolone at a dose of 6 mg/kg/d showed better maintenance of effect compared with vamorolone at a dose of 2 mg/kg/d for most (3/5) motor outcomes. Bone morbidities of prednisone (stunting of growth and declines in serum bone biomarkers) were reversed when treatment transitioned to vamorolone. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT03439670. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for boys with DMD, the efficacy of vamorolone at a dose of 6 mg/kg/d was maintained over 48 weeks.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.949
Threshold uncertainty score0.417

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.004
GPT teacher head0.214
Teacher spread0.210 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations70
Published2024
Admission routes1
Has abstractyes

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