Pivotal trial of vamorolone in Duchenne muscular dystrophy
瓦莫龙治疗杜氏肌营养不良症的关键试验
基本信息
- 批准号:9767888
- 负责人:
- 金额:$ 149.91万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-02-15 至 2020-08-31
- 项目状态:已结题
- 来源:
- 关键词:7 year oldAdrenal Cortex HormonesAdrenal GlandsAdverse drug effectAdverse effectsAffinityAgeAgonistAgreementAnti-inflammatoryAutoimmune ProcessAwardBecker Muscular DystrophyBindingBiological MarkersBlindedBody mass indexCapitalChemistryChildClinicalClinical ResearchClinical TrialsControlled StudyDermatomyositisDevelopmentDoseDouble-Blind MethodDrug KineticsDuchenne muscular dystrophyEnrollmentEssential DrugsEuropeanExerciseFormulationFoundationsFundingFutureGeneticGenetic TranscriptionGlucocorticoid ReceptorGlucocorticoidsGoalsGovernmentGrantGrowthHalf-LifeHydrocortisoneInsulin ResistanceInternationalLabelLeadershipLegal patentMarketingMeasuresMediatingMineralocorticoid ReceptorMonitorNR3C1 geneNR3C2 geneNational Institute of Neurological Disorders and StrokeNeuromuscular DiseasesOsteopeniaOutcomeOutcome MeasurePamphletsPatientsPharmaceutical PreparationsPharmacodynamicsPhasePlacebosPrednisoneProgram DevelopmentProtocols documentationQuality of lifeRandomizedRare DiseasesResearchResearch ContractsResearch PersonnelRisk ManagementSafetySalesSmall Business Innovation Research GrantSteroidsStructureTestingTherapeutics for Rare and Neglected DiseasesTimeToxicologyTransactivationUnited States National Institutes of HealthWeight Gainactigraphybiomarker panelbone fragilitybone turnoverboysclinical developmentclinical efficacycommercializationcommunity settingdeflazacortdrug developmentimprovedinnovationmHealthneuromuscularnoveloff-patentopen labelpaymentpharmacodynamic biomarkerpharmacokinetics and pharmacodynamicsphase III trialpreclinical developmentpreservationprogramsresearch clinical testingstandard of caretooltrial design
项目摘要
Abstract
ReveraGen BioPharma is a clinical stage drug development company that is developing vamorolone (VBP15),
a first-in-class dissociative steroidal drug. The initial indication being tested is Duchenne muscular dystrophy
(DMD), where vamorolone holds promise for retaining or increasing efficacy of glucocorticoids, while reducing
adverse effects (bone fragility, stunting of growth, weight gain, insulin resistance). ReveraGen received a
NINDS SBIR Phase II grant in support of the Phase 2a studies in 4 to <7 year old DMD boys in 2016 (protocols
VBP15-002; VBP15-003) (R44NS095423). The original trial was planned for four dose groups, with 2-6 boys
per dose group (up to 24 patients). After award of the grant, the size of the trial was increased to 48 DMD
boys (12 per dose group; n=48). Despite the narrow age range in a rare disease, the trial was fully enrolled
within 15 months, and the Phase 2a study completed in November 2017, within the time frame of the SBIR
Phase II grant (15 February 2016-31 January 2018). All doses were well-tolerated (0.25 mg/k/gday – 6.0
mg/kg/day; or to 10-times the typical prednisone dose in DMD boys). Pharmacokinetics showed a well-
behaved drug, with PK similar to corticosteroids (short half-life of 2-3 hrs, and no drug accumulation between
doses). There was no significant change in body mass index (primary clinical safety outcome relative to
prednisone). Pharmacodynamic biomarker results showed improved safety compared to corticosteroids, with
no evidence of insulin resistance at any dose, and a >10 fold improved safety margin for bone turnover and
adrenal suppression. Here, we request partial support for the pivotal double blind Phase 2b study of 120 DMD
boys, ages 4 to <7 years. The Phase 2b study (VBP15-004) includes four groups with six months treatment
(placebo, prednisone, low dose vamorolone, high dose vamorolone), followed by an additional 6 months
treatment with two dose levels of vamorolone. Co-funding for the Phase 2b study is from the European
Commission ($7M Horizons 2020 grant awarded in 2016), venture philanthropy support by non-profit
foundations, and an option agreement for future sales and marketing. Aim 1 is to test 6 months of treatment
of two dose levels of vamorolone, with efficacy (time to stand) vs. placebo, and safety (change in body mass
index) vs. prednisone. Aim 2 is to bridge pharmacodynamic biomarkers to clinical outcomes of both safety and
efficacy. Anticipated new matching funding during the proposed award period includes a 2nd milestone
payment on the option agreement ($15M August 2018). The completion of the proposed Phase IIB SBIR
research will lead to discussions with the FDA regarding possible accelerated approval, with Phase III trials in
the post-marketing period. The bridging of novel safety and efficacy biomarkers to clinical outcomes will
enable the utilization of these biomarkers to expand labeling to younger DMD children (0-4 years), and efficient
testing of vamorolone for treatment of new indications (eg. Becker muscular dystrophy, juvenile
dermatomyositis), thus providing the potential to significantly augment the treatment options and quality of life
for patients with genetic and autoimmune neuromuscular disorders.
摘要
项目成果
期刊论文数量(0)
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Paula R Clemens其他文献
Paula R Clemens的其他文献
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{{ truncateString('Paula R Clemens', 18)}}的其他基金
Vamorolone trial in Becker muscular dystrophy
贝克尔肌营养不良症的瓦莫洛龙试验
- 批准号:
10277734 - 财政年份:2021
- 资助金额:
$ 149.91万 - 项目类别:
Pilot Trial of Vamorolone for the Treatment of Becker Muscular Dystrophy
瓦莫洛龙治疗贝克尔肌营养不良症的初步试验
- 批准号:
10215387 - 财政年份:2020
- 资助金额:
$ 149.91万 - 项目类别:
Pilot Trial of Vamorolone for the Treatment of Becker Muscular Dystrophy
瓦莫洛龙治疗贝克尔肌营养不良症的初步试验
- 批准号:
10437669 - 财政年份:2020
- 资助金额:
$ 149.91万 - 项目类别:
Establishing a Cost-effective Return of Results to Parents of Boys in VISION-DMD Clinical Trials
在 VISION-DMD 临床试验中建立具有成本效益的结果返回给男孩父母
- 批准号:
9929267 - 财政年份:2019
- 资助金额:
$ 149.91万 - 项目类别:
Network of Excellence in Neuroscience Clinical Trials (University of Pittsburgh CRS)
神经科学临床试验卓越网络(匹兹堡大学 CRS)
- 批准号:
10742528 - 财政年份:2018
- 资助金额:
$ 149.91万 - 项目类别:
Network of Excellence in Neuroscience Clinical Trials (University of Pittsburgh CRS)
神经科学临床试验卓越网络(匹兹堡大学 CRS)
- 批准号:
10604634 - 财政年份:2018
- 资助金额:
$ 149.91万 - 项目类别:
Network of Excellence in Neuroscience Clinical Trials (University of Pittsburgh CRS)
神经科学临床试验卓越网络(匹兹堡大学 CRS)
- 批准号:
10163275 - 财政年份:2018
- 资助金额:
$ 149.91万 - 项目类别:
Phase IIa study of VBP15 for Duchenne muscular dystrophy
VBP15 治疗杜氏肌营养不良症的 IIa 期研究
- 批准号:
9047701 - 财政年份:2016
- 资助金额:
$ 149.91万 - 项目类别:
VBP15, an Innovative Steroid-like Intervention on DMD: VISION-DMD
VBP15,一种针对 DMD 的创新类固醇干预措施:VISION-DMD
- 批准号:
8960452 - 财政年份:2015
- 资助金额:
$ 149.91万 - 项目类别:
Becker muscular dystrophy: A natural history study to predict efficacy of exon sk
贝克尔肌营养不良症:预测外显子 sk 功效的自然史研究
- 批准号:
8102468 - 财政年份:2011
- 资助金额:
$ 149.91万 - 项目类别: