Long-term Extension Study to Assess Vamorolone in Boys With Duchenne Muscular Dystrophy (DMD)

NCT ID: NCT03038399

Last Updated: 2021-05-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-02-02
• Study Completion Date: 2020-04-30

Brief Summary

This long-term extension study is an open-label, multiple-dose study to evaluate the long-term safety, tolerability, efficacy and PD of vamorolone administered once daily by liquid oral suspension over a Treatment Period of 24 months to young boys with DMD who participated in the VBP15-002 Phase IIa and VBP15-003 Phase IIa extension core studies.

Detailed Description

This study will evaluate if it is safe to use a new medication called vamorolone for more than two weeks in children with DMD, if boys with DMD who take the study medication have improved muscle function compared to boys with DMD in other studies who did not take any type of steroid, and to see if boys with DMD who take the study medication gain less weight compared to boys with DMD in a prior study who took another type of steroid called prednisone. Enrolled participants will take the study medication for 24 months.

Conditions

Duchenne Muscular Dystrophy

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dose Level Group 1

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

Group Type: EXPERIMENTAL

Vamorolone 0.25 mg/day/day

Intervention Type: DRUG

Oral administration of 0.25 mg/kg/day daily for 24 months.

Dose Level Group 2

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

Group Type: EXPERIMENTAL

Vamorolone 0.75 mg/day/day

Intervention Type: DRUG

Oral administration of 0.75 mg/kg/day daily for 24 months.

Dose Level Group 3

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

Group Type: EXPERIMENTAL

Vamorolone 2.0 mg/day/day

Intervention Type: DRUG

Oral administration of 2.0 mg/kg/day daily for 24 months.

Dose Level Group 4

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

Group Type: EXPERIMENTAL

Vamorolone 6.0 mg/day/day

Intervention Type: DRUG

Oral administration of 6.0 mg/kg/day daily for 24 months.

Interventions

Vamorolone 0.25 mg/day/day

Oral administration of 0.25 mg/kg/day daily for 24 months.

Intervention Type: DRUG

Vamorolone 0.75 mg/day/day

Oral administration of 0.75 mg/kg/day daily for 24 months.

Intervention Type: DRUG

Vamorolone 2.0 mg/day/day

Oral administration of 2.0 mg/kg/day daily for 24 months.

Intervention Type: DRUG

Vamorolone 6.0 mg/day/day

Oral administration of 6.0 mg/kg/day daily for 24 months.

Intervention Type: DRUG

Other Intervention Names

VBP15; VBP15; VBP15; VBP15

Eligibility Criteria

Inclusion Criteria

1. Subject's parent or legal guardian has provided written informed consent and HIPAA authorization (if applicable) prior to any VBP15-LTE long-term extension study-specific procedures;

2. Subject has previously completed study VBP15-003 up to and including the Week 24 Final assessments, prior to enrolling in the VBP15-LTE study at the conclusion of the VBP15-003 Week 24 Visit [Note: if entering the dose-tapering period, subject is enrolling within 8 weeks after the VBP15-003 final visit following dose-tapering]; and

3. Subject and parent/guardian are willing and able to comply with scheduled visits, study drug administration plan, and study procedures.

Exclusion Criteria

1. Subject had a serious or severe adverse event in study VBP15-003 that, in the opinion of the Investigator, was probably or definitely related to vamorolone use and precludes safe use of vamorolone for the subject in this long-term extension study;

2. Subject has current or history of major renal or hepatic impairment, diabetes mellitus or immunosuppression;

3. Subject has current or history of chronic systemic fungal or viral infections;

4. 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;

5. Subject has evidence of symptomatic cardiomyopathy. [Note: Asymptomatic cardiac abnormality on investigation would not be exclusionary];

6. 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 glucocorticoids 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];

7. Subject has used idebenone within 4 weeks prior to the first dose of study medication;

8. Subject has an allergy or hypersensitivity to the study medication or to any of its constituents;

9. Subject has severe behavioral or cognitive problems that preclude participation in the study, in the opinion of the Investigator;

10. 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

11. Subject is currently taking any investigational drug, or has taken any investigational drug other than vamorolone within 3 months prior to the start of study treatment.

Note: Subjects may be re-evaluated if ineligible due to a transient condition which would prevent the subject from participating.

• Minimum Eligible Age: 4 Years
• Maximum Eligible Age: 7 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

University of Pittsburgh

OTHER

Sponsor Role: collaborator

Cooperative International Neuromuscular Research Group

NETWORK

Sponsor Role: collaborator

ReveraGen BioPharma, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Paula R Clemens, MD

Role: STUDY_CHAIR

University of Pittsburgh

Locations

University of California Davis

Davis, California, United States

University of Florida

Gainesville, Florida, United States

Nemours Children's Hospital

Orlando, Florida, United States

Ann & Robert H. Lurie Children's Hospital

Chicago, Illinois, United States

Duke University

Durham, North Carolina, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Royal Children's Hospital

Melbourne, , Australia

Sydney Children's Hospital

Westmead, , Australia

Alberta Children's Hospital

Calgary, Alberta, Canada

Schneider Children's Medical Center

Petah Tikva, , Israel

Queen Silvia Children's Hospital

Gothenburg, , Sweden

Newcastle upon Tyne Hospitals NHS Foundation Trust

Newcastle upon Tyne, , United Kingdom

Countries

United States; Australia; Canada; Israel; Sweden; United Kingdom

References

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.

Reference Type: RESULT

PMID: 32956407 (View on PubMed)

Mah JK, Clemens PR, Guglieri M, Smith EC, Finkel RS, Tulinius M, Nevo Y, Ryan MM, Webster R, Castro D, Kuntz NL, McDonald CM, Damsker JM, Schwartz BD, Mengle-Gaw LJ, Jackowski S, Stimpson G, Ridout DA, Ayyar-Gupta V, Baranello G, Manzur AY, Muntoni F, Gordish-Dressman H, Leinonen M, Ward LM, Hoffman EP, Dang UJ; NorthStar UK Network and CINRG DNHS Investigators. Efficacy and Safety of Vamorolone in Duchenne Muscular Dystrophy: A 30-Month Nonrandomized Controlled Open-Label Extension Trial. JAMA Netw Open. 2022 Jan 4;5(1):e2144178. doi: 10.1001/jamanetworkopen.2021.44178.

Reference Type: DERIVED

PMID: 35076703 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Related Links

https://pubmed.ncbi.nlm.nih.gov/32956407/

Link to publication

Other Identifiers

VBP15-LTE

Identifier Type: -

Identifier Source: org_study_id