A Study to Assess the Efficacy and Safety of Vamorolone in Boys With Duchenne Muscular Dystrophy (DMD)

NCT03439670 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: VBP15-004
• Study Type: interventional
• Target: 121
• Locations: 11 countries
• Sites: 33

Brief Summary

Brief Summary: This Phase IIb study is a randomized, double-blind, parallel group, placebo and active-controlled study to evaluate the efficacy, safety, PD, and population PK of vamorolone administered orally at daily doses of 2.0 mg/kg and 6.0 mg/kg versus prednisone 0.75 mg/kg/day and placebo over a Treatment Period of 24 weeks, and to evaluate persistence of effect over a Treatment Period of 48 weeks in ambulant boys ages 4 to \<7 years with DMD.

Conditions

Duchenne Muscular Dystrophy

Keywords

Duchenne Muscular Dystrophy; Vamorolone

Outcome Measures

Primary Outcomes (1)

• Efficacy Measured by Time to Stand Test (TTSTAND) Velocity in Rises/Second Change From Baseline

  Vamorolone at 6.0mg/kg/day vs. placebo group in change from baseline to the Week 24 assessment

  24 weeks

Study Arms (6)

Treatment Group 1

EXPERIMENTAL

Patients enrolled in Treatment Group 1 (experimental group) will receive vamorolone 2.0 mg/kg/day for the duration of the study.

Drug: Vamorolone

Treatment Group 2

EXPERIMENTAL

Patients enrolled in Treatment Group 2 (experimental group) will receive vamorolone at 6.0 mg/kg/day for the duration of the study.

Drug: Vamorolone

Treatment Group 3

ACTIVE COMPARATOR

Patients enrolled in Treatment Group 3 (active comparator group) will receive prednisone 0.75 mg/kg/day for 24 weeks followed by 20 weeks of treatment with 2.0 mg/kg/day vamorolone.

Drug: Prednisone; Drug: Vamorolone

Treatment Group 4

ACTIVE COMPARATOR

Patients enrolled in Treatment Group 4 (active comparator group) will receive prednisone 0.75 mg/kg/day for 24 weeks followed by 20 weeks treatment with 6.0 mg/kg/day vamorolone.

Drug: Prednisone; Drug: Vamorolone

Treatment Group 5

PLACEBO COMPARATOR

Patients enrolled in Treatment Group 5 (placebo comparator group) will receive placebo daily for 24 weeks followed by 20 weeks treatment with 2.0 mg/kg/day vamorolone.

Other: Placebo; Drug: Vamorolone

Treatment Group 6

PLACEBO COMPARATOR

Patients enrolled in Treatment Group 6 (placebo comparator group) will receive placebo daily for 24 weeks followed by 20 weeks treatment with 6.0 mg/kg/day vamorolone.

Other: Placebo; Drug: Vamorolone

Interventions

Vamorolone DRUG

Oral administration of 2.0 mg/kg/day for the duration of the study.

Also known as: VBP15

Treatment Group 1

Prednisone DRUG

Oral administration of 0.75 mg/kg/day for 24 weeks.

Treatment Group 3

Placebo OTHER

Oral administration of placebo daily for 24 weeks.

Treatment Group 5

Eligibility Criteria

• Age: 4 Years - 7 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Subject's parent(s) or legal guardian(s) has (have) provided written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization, where applicable, prior to any study-related procedures; participants will be asked to give written or verbal assent according to local requirements
• Subject has a centrally confirmed (by TRiNDS central genetic counselor\[s\]) diagnosis of DMD as defined as:
• Dystrophin immunofluorescence and/or immunoblot showing complete dystrophin deficiency, and clinical picture consistent with typical DMD, OR
• Identifiable mutation within the DMD gene (deletion/duplication of one or more exons), where reading frame can be predicted as 'out-of-frame,' and clinical picture consistent with typical DMD, OR
• Complete dystrophin gene sequencing showing an alteration (point mutation, duplication, other) that is expected to preclude production of the dystrophin protein (i.e., nonsense mutation, deletion/duplication leading to a downstream stop codon), with a clinical picture consistent with typical DMD;
• Subject is ≥ 4 years and \<7 years of age at time of enrollment in the study;
• Subject weighs \>13.0 kg and ≤ 39.9 kg at the Screening Visit;
• Subject is able to walk independently without assistive devices;
• Subject is able to complete the Time to Stand Test (TTSTAND) without assistance in \<10 seconds, as assessed at the Screening Visit;
• Clinical laboratory test results are within the normal range at the Screening Visit, or if abnormal, are not clinically significant, in the opinion of the Investigator. \[Notes: Serum gamma glutamyl transferase (GGT), creatinine, and total bilirubin all must be ≤ upper limit of the normal range at the Screening Visit. An abnormal vitamin D level that is considered clinically significant will not exclude a subject from randomization\];
• Subject has evidence of chicken pox immunity as determined by:
• Presence of IgG antibodies to varicella, as documented by a positive test result from the local laboratory from blood collected during the Screening Period, OR
• Documentation, provided at the Screening Visit, that the subject has had 2 doses of varicella vaccine, with or without serologic evidence of immunity; the second of the 2 immunizations must have been given at least 14 days prior to randomization.
• Subject is able to swallow tablets, as confirmed by successful test swallowing of placebo tablets during the Screening Period; and
• Subject and parent(s)/guardian(s) are willing and able to comply with scheduled visits, study drug administration plan, and study procedures.

You may not qualify if:

• Subject has current or history of major renal or hepatic impairment, diabetes mellitus or immunosuppression;
• Subject has current or history of chronic systemic fungal or viral infections;
• Subject has had an acute illness within 4 weeks prior to the first dose of study medication;
• Subject has used mineralocorticoid receptor agents, such as spironolactone, eplerenone, canrenone (canrenoate potassium), prorenone (prorenoate potassium), mexrenone (mexrenoate potassium) within 4 weeks prior to the first dose of study medication;
• Subject has a history of primary hyperaldosteronism;
• Subject is currently being treated or has received previous treatment with oral glucocorticoids or other immunosuppressive agents \[Notes: Past transient use of oral glucocorticoids or other oral immunosuppressive agents for no longer than 1 month cumulative, with last use at least 3 months prior to first dose of study medication, will be considered for eligibility on a case-by-case basis, unless discontinued for intolerance. Inhaled and/or topical glucocorticoids are permitted if last use is at least 4 weeks prior to first dose of study medication or if administered at stable dose beginning at least 4 weeks prior to first dose of study medication and anticipated to be used at the stable dose regimen for the duration of the study\];
• Subject has an allergy or hypersensitivity to the study medication or to any of its constituents;
• Subject has used idebenone within 4 weeks prior to the first dose of study medication;
• Subject has severe behavioral or cognitive problems that preclude participation in the study, in the opinion of the Investigator;
• Subject has previous or ongoing medical condition, medical history, physical findings or laboratory abnormalities that could affect safety, make it unlikely that treatment and follow-up will be correctly completed or impair the assessment of study results, in the opinion of the Investigator;
• Subject is taking (or has taken within 4 weeks prior to the first dose of study medication) herbal remedies and supplements which can impact muscle strength and function (e.g., Co-enzyme Q10, creatine, etc);
• Subject is taking (or has taken within 3 months prior to the first dose of study medication) any medication indicated for DMD, including Exondys51 and Translarna;
• Subject has been administered a live attenuated vaccine within 14 days prior to the first dose of study medication;
• Subject is currently taking any other investigational drug or has taken any other investigational drug within 3 months prior to the first dose of study medication;
• Subject has a sibling who is currently enrolled in any vamorolone study or Expanded Access Program, or who intends to enroll in any vamorolone study or Expanded Access Program during the subject's participation in the VBP15-004 study; or

Sponsors & Collaborators

• ReveraGen BioPharma, Inc.: lead
• European Union: collaborator
• Cooperative International Neuromuscular Research Group: collaborator
• Newcastle University: collaborator
• University of Pittsburgh: collaborator

Study Sites (33)

University of California Davis

Davis, California, 95616, United States

Location

University of California Los Angeles

Los Angeles, California, 90095, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Nemours Children's Hospital

Orlando, Florida, 32827, United States

Location

Ann & Robert H. Lurie Children's Hospital

Chicago, Illinois, 60611, United States

Location

Gillette Children's Speciality Health Care

Saint Paul, Minnesota, 55101, United States

Location

Duke Children's Hospital

Durham, North Carolina, 27710, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75207, United States

Location

Children's Hospital of Virginia of Virginia Commonwealth University

Richmond, Virginia, 23219, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Royal Children's Hospital

Melbourne, Australia

Location

Sydney Children's Hospital

Westmead, Australia

Location

Ghent University Hospital

Ghent, Belgium

Location

University Hospitals Leuven

Leuven, Belgium

Location

Alberta's Children Hospital

Calgary, Alberta, AB T3B 6A8, Canada

Location

British Columbia Children's Hospital

Vancouver, British Columbia, V6H 3N1, Canada

Location

Children's Hospital of Eastern Ontario

Ottawa, Ontario, K1H 8L1, Canada

Location

Montreal Children's Hospital

Montreal, Quebec, H4A 3J1, Canada

Location

University Hospital Brno

Brno, Czechia

Location

Charles University

Prague, Czechia

Location

Agia Sofia Children's Hospital

Athens, Greece

Location

Schneider Children's Medical Center

Petah Tikvah, 49202, Israel

Location

Leiden University Medical Center

Leiden, Netherlands

Location

Radboud University

Nijmegen, Netherlands

Location

Sant Joan de Deu Hospital - Barcelona, Spain

Barcelona, Spain

Location

Hospital Universitario y Politécnico La Fe

Valencia, Spain

Location

Queen Silvia Children's Hospital

Gothenburg, 41685, Sweden

Location

Birmingham Heartlands Hospital

Birmingham, United Kingdom

Location

Royal Hospital for Children

Glasgow, G51 4TF, United Kingdom

Location

Leeds Teaching Hospital Trust

Leeds, United Kingdom

Location

Alder Hey Children's NHS Foundation Trust

Liverpool, L12 2AP, United Kingdom

Location

Great Ormond Street Hospital

London, United Kingdom

Location

Newcastle upon Tyne Hospitals NHS Foundation Trust

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

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  PMID: 36036925 RESULT

• de Vera A, Clemens PR, Dang UJ, Dutreix C, Gresko E, Guglieri M, Hagerty L, Hasham S, Damsker J, Hathout Y, Linden A, Berglund A, Tobin R, Wahbi K, Hoffman EP. Mineralocorticoid receptor antagonism of vamorolone: Evidence from LIONHEART and VISION-DMD clinical trials. Steroids. 2025 Nov;223:109689. doi: 10.1016/j.steroids.2025.109689. Epub 2025 Sep 14.

  PMID: 40957504 DERIVED

• Dang UJ, Damsker JM, Guglieri M, Clemens PR, Perlman SJ, Smith EC, Horrocks I, Finkel RS, Mah JK, Deconinck N, Goemans NM, Haberlova J, Straub V, Mengle-Gaw L, Schwartz BD, Harper A, Shieh PB, De Waele L, Castro D, Yang ML, Ryan MM, McDonald CM, Tulinius M, Webster RI, Mcmillan HJ, Kuntz N, Rao VK, Baranello G, Spinty S, Childs AM, Sbrocchi AM, Selby KA, Monduy M, Nevo Y, Vilchez JJ, Nascimento-Osorio A, Niks EH, De Groot IJM, Katsalouli M, Van Den Anker JN, Ward LM, Leinonen M, D'Alessandro AL, Hoffman EP. Efficacy and Safety of Vamorolone Over 48 Weeks in Boys With Duchenne Muscular Dystrophy: A Randomized Controlled Trial. Neurology. 2024 Mar 12;102(5):e208112. doi: 10.1212/WNL.0000000000208112. Epub 2024 Feb 9.

  PMID: 38335499 DERIVED

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne

Interventions

VBP15 compound; Prednisone

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Dr. Eric Hoffman
• Organization: ReveraGen BioPharma Inc.

ericphoffman@gmail.com

301-762-7980

Study Officials

• Michela Guglieri, M.D.

  John Walton Muscular Dystrophy Research Centre

  STUDY CHAIR

• Paula Clemens, M.D.

  University of Pittsburgh

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2018
• First Posted: February 20, 2018
• Study Start: June 29, 2018
• Primary Completion: February 23, 2021
• Study Completion: August 19, 2021
• Last Updated: March 9, 2023
• Results First Posted: July 13, 2022

Record last verified: 2023-03

Locations

ES (2); GR (1); GB (6); BE (2); NL (2); IL (1); CA (4); US (10); CZ (2); AU (2); SE (1)