A Study to Assess Vamorolone in Boys With Duchenne Muscular Dystrophy (DMD)

NCT02760264 | Completed Phase 2 Results DMC

• 3 other identifiers: VBP15-0021R44NS095423-011U34AR068616-01
• Study Type: interventional
• Target: 48
• Locations: 6 countries
• Sites: 12

Brief Summary

The purpose of this study is to determine whether a new medication called vamorolone is safe and well-tolerated by boys with Duchenne muscular dystrophy (DMD) ages ≥ 4 and \< 7 years old.

Conditions

Duchenne Muscular Dystrophy

Keywords

Duchenne Muscular Dystrophy; vamorolone

Outcome Measures

Primary Outcomes (1)

• Overall Summary of Adverse Events as Assessed by CTCAE Version 4.03

  Treatment-emergent adverse events (TEAEs) are defined as any adverse event or worsening of an existing conditions after initiation of the investigational product and through the subject's last study visit (study completion or early termination). Serious adverse events were recorded for up to 30 days after the final administration of study drug. Note: Total Number of Treatment Emergent Adverse Events: The total incidences of TEAEs experienced in study; Any Treatment Emergent Adverse Event: TEAEs reported at least once per dose group

  Adverse events will be recorded from the date of informed consent and through the time of the subject's last study visit. Serious adverse events will be recorded from the date of informed consent and for up to 30 days after final drug administration.

Secondary Outcomes (15)

• Serum Pharmacodynamic Biomarkers (Insulin Resistance)- Fasting Glucose

  Baseline, Week 2

• Serum Pharmacodynamic Biomarkers (Insulin Resistance) -Fasting Glucose

  Baseline, Week 2

• Serum Pharmacodynamic Biomarkers (Insulin Resistance)- Insulin

  Baseline , Week 2

• Serum Pharmacodynamic Biomarkers (Insulin Resistance)- Insulin

  Baseline, Week 2

• Serum Pharmacodynamic Biomarkers (Adrenal Axis Suppression)- First in Morning Cortisol

  Week 2 (pre-dose)

Study Arms (4)

Dose Level Group 1

EXPERIMENTAL

Participants enrolled in Dose Level Group 1 will receive vamorolone 0.25 mg/kg/day.

Drug: Vamorolone 0.25 mg/kg/day

Dose Level Group 2

EXPERIMENTAL

Participants enrolled in Dose Level Group 2 will receive vamorolone 0.75 mg/kg/day.

Drug: Vamorolone 0.75 mg/kg/day

Dose Level Group 3

EXPERIMENTAL

Participants enrolled in Dose Level Group 3 will receive vamorolone 2.0 mg/kg/day.

Drug: Vamorolone 2.0 mg/kg/day

Dose Level Group 4

EXPERIMENTAL

Participants enrolled in Dose Level Group 4 will receive vamorolone 6.0 mg/kg/day.

Drug: Vamorolone 6.0 mg/kg/day

Interventions

Vamorolone 0.25 mg/kg/day DRUG

Oral administration of 0.25 mg/kg/day daily for 14 days.

Also known as: VBP15

Dose Level Group 1

Vamorolone 0.75 mg/kg/day DRUG

Oral administration of 0.75 mg/kg/day daily for 14 days.

Also known as: VBP15

Dose Level Group 2

Vamorolone 2.0 mg/kg/day DRUG

Oral administration of 2.0 mg/kg/day daily for 14 days.

Also known as: VBP15

Dose Level Group 3

Vamorolone 6.0 mg/kg/day DRUG

Oral administration of 6 mg/kg/day daily for 14 days.

Also known as: VBP15

Dose Level Group 4

Eligibility Criteria

• Age: 4 Years - 6 Years
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Subject's parent or legal guardian has provided written informed consent/Health Insurance Portability and Accountability Act (HIPAA) authorization prior to any study-related procedures;
• Subject has a confirmed (by Central Genetic Counselor) 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 typical clinical picture of DMD;
• Subject is ≥ 4 years and \< 7 years of age at time of enrollment in the study;
• Subject is able to complete the Time to Stand Test (TTSTAND) without assistance, as assessed at the Screening and Baseline Visits;
• 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. (Note: Serum gamma glutamyl transferase \[GGT\], creatinine, and total bilirubin all must be ≤ upper limit of the normal range at the Screening Visit);
• 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 testing laboratory at the Screening Visit; and
• Subject and parent/guardian 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 is currently being treated or has received previous treatment with oral glucocorticoids or other immunosuppressive agents. \[Notes: Past transient use of oral glucocorticoids or other oral immunosuppressive agents for no longer than 3 months cumulative, with last use at least 3 months prior to first dose of study medication, will be considered for eligibility on a case-by-case basis. Inhaled and/or topical corticosteroids prescribed for an indication other than DMD are permitted but must be administered at stable dose for at least 3 months prior to study drug administration\];
• Subject has used idebenone within 4 weeks prior to the first dose of study medication;
• Subject has an allergy or hypersensitivity to the study medication or to any of its constituents;
• 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 any other investigational drug currently or has taken any other investigational drug within 3 months prior to the start of study treatment; or
• Subject has previously been enrolled in the study.

Sponsors & Collaborators

• ReveraGen BioPharma, Inc.: lead
• University of Pittsburgh: collaborator
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): collaborator
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• Cooperative International Neuromuscular Research Group: collaborator

Study Sites (12)

University of California Davis

Davis, California, 95616, United States

Location

University of Florida

Gainesville, Florida, 32611, 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

Duke University

Durham, North Carolina, 27710, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75207, United States

Location

Royal Children's Hospital

Melbourne, Australia

Location

Sydney Children's Hospital

Westmead, Australia

Location

Alberta Children's Hospital

Calgary, Alberta, T3B 6A8, Canada

Location

Schneider Children's Medical Center

Petah Tikvah, 49202, Israel

Location

Queen Silvia Children's Hospital

Gothenburg, 41685, Sweden

Location

Newcastle upon Tyne Hospitals NHS Foundation Trust

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Related Publications (3)

• Hoffman E, Gaglianone S, Ketema R, Tu W, Peay H, Clemens P, Dang U, Conklin L. Return of participant-level clinical trial results to participants: pilot of a simplified centralised approach. BMJ Open. 2024 Mar 23;14(3):e080097. doi: 10.1136/bmjopen-2023-080097.

  PMID: 38521535 DERIVED

• Smith EC, Conklin LS, Hoffman EP, Clemens PR, Mah JK, Finkel RS, Guglieri M, Tulinius M, Nevo Y, Ryan MM, Webster R, Castro D, Kuntz NL, Kerchner L, Morgenroth LP, Arrieta A, Shimony M, Jaros M, Shale P, Gordish-Dressman H, Hagerty L, Dang UJ, Damsker JM, Schwartz BD, Mengle-Gaw LJ, McDonald CM; CINRG VBP15 and DNHS Investigators. Efficacy and safety of vamorolone in Duchenne muscular dystrophy: An 18-month interim analysis of a non-randomized open-label extension study. PLoS Med. 2020 Sep 21;17(9):e1003222. doi: 10.1371/journal.pmed.1003222. eCollection 2020 Sep.

  PMID: 32956407 DERIVED

• Li X, Conklin LS, van den Anker J, Hoffman EP, Clemens PR, Jusko WJ. Exposure-Response Analysis of Vamorolone (VBP15) in Boys With Duchenne Muscular Dystrophy. J Clin Pharmacol. 2020 Oct;60(10):1385-1396. doi: 10.1002/jcph.1632. Epub 2020 May 20.

  PMID: 32434278 DERIVED

Related Links

• Cooperative International Research Group
• ReveraGen BioPharma, Inc
• Phase IIa trial in Duchenne muscular dystrophy shows vamorolone is a first-in-class dissociative steroidal anti-inflammatory drug.

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne

Interventions

VBP15 compound

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

Results Point of Contact

• Title: Dr. Eric P. Hoffman
• Organization: ReveraGen Biopharma Inc.

ericphoffman@gmail.com

240-672-0295

Study Officials

• Paula R Clemens, MD

  University of Pittsburgh

  STUDY CHAIR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2016
• First Posted: May 3, 2016
• Study Start: June 1, 2016
• Primary Completion: May 1, 2018
• Study Completion: May 1, 2018
• Last Updated: January 2, 2019
• Results First Posted: January 2, 2019

Record last verified: 2018-12

Locations

CA (1); US (6); IL (1); SE (1); AU (2); GB (1)