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

• ClinicalTrials.gov Identifier: NCT03038399
• Recruitment Status: Completed
• First Posted: January 31, 2017
• Results First Posted: May 20, 2021
• Last Update Posted: May 20, 2021
• Sponsor: ReveraGen BioPharma, Inc.
• Collaborators: University of Pittsburgh; Cooperative International Neuromuscular Research Group
• Information provided by (Responsible Party): ReveraGen BioPharma, Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Duchenne Muscular Dystrophy	Drug: Vamorolone 0.25 mg/day/day; Drug: Vamorolone 0.75 mg/day/day; Drug: Vamorolone 2.0 mg/day/day; Drug: Vamorolone 6.0 mg/day/day	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 46 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A 24-month Phase II Open-label, Multicenter Long-term Extension Study to Assess the Long-Term Safety and Efficacy of Vamorolone in Boys With Duchenne Muscular Dystrophy (DMD)
• Actual Study Start Date: February 2, 2017
• Actual Primary Completion Date: April 30, 2020
• Actual Study Completion Date: April 30, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Dose Level Group 1; Participants enrolled in Dose Level Group 1 will receive vamorolone 0.25 mg/kg/day.	Drug: Vamorolone 0.25 mg/day/day; Oral administration of 0.25 mg/kg/day daily for 24 months.; Other Name: VBP15
Experimental: Dose Level Group 2; Participants enrolled in Dose Level Group 2 will receive vamorolone 0.75 mg/kg/day.	Drug: Vamorolone 0.75 mg/day/day; Oral administration of 0.75 mg/kg/day daily for 24 months.; Other Name: VBP15
Experimental: Dose Level Group 3; Participants enrolled in Dose Level Group 3 will receive vamorolone 2.0 mg/kg/day.	Drug: Vamorolone 2.0 mg/day/day; Oral administration of 2.0 mg/kg/day daily for 24 months.; Other Name: VBP15
Experimental: Dose Level Group 4; Participants enrolled in Dose Level Group 4 will receive vamorolone 6.0 mg/kg/day.	Drug: Vamorolone 6.0 mg/day/day; Oral administration of 6.0 mg/kg/day daily for 24 months.; Other Name: VBP15

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE Version 4.03 [ Time Frame: 24 months ]
   To evaluate the long-term safety and tolerability of vamorolone, administered orally at daily doses up to 6.0 mg/kg/day over a 24- month Treatment Period, in boys ages 4-7 years with DMD; 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);
2. Total Number of Adverse Events as Assessed by CTCAE Version 4.03 [ Time Frame: 24 Months ]
   To evaluate the long-term safety and tolerability of vamorolone, administered orally at daily doses up to 6.0 mg/kg/day over a 24-month Treatment Period, in boys ages 4-7 years with DMD. 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).

Eligibility Criteria

• Ages Eligible for Study: 4 Years to 7 Years (Child)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, California

University of California Davis

Davis, California, United States, 95616

United States, Florida

University of Florida

Gainesville, Florida, United States, 32611

Nemours Children's Hospital

Orlando, Florida, United States, 32827

United States, Illinois

Ann & Robert H. Lurie Children's Hospital

Chicago, Illinois, United States, 60611

United States, North Carolina

Duke University

Durham, North Carolina, United States, 27710

United States, Texas

University of Texas Southwestern Medical Center

Dallas, Texas, United States, 75207

Australia

Royal Children's Hospital

Melbourne, Australia

Sydney Children's Hospital

Westmead, Australia

Canada, Alberta

Alberta Children's Hospital

Calgary, Alberta, Canada, T3B 6A8

Israel

Schneider Children's Medical Center

Petah Tikwah, Israel, 49202

Sweden

Queen Silvia Children's Hospital

Gothenburg, Sweden, 41685

United Kingdom

Newcastle upon Tyne Hospitals NHS Foundation Trust

Newcastle upon Tyne, United Kingdom, NE7 7DN

Sponsors and Collaborators

ReveraGen BioPharma, Inc.

University of Pittsburgh

Cooperative International Neuromuscular Research Group

Investigators

• Study Chair: Paula R Clemens, MD; University of Pittsburgh

  Study Documents (Full-Text)

Documents provided by ReveraGen BioPharma, Inc.:

Study Protocol  [PDF] October 3, 2018

Statistical Analysis Plan  [PDF] June 21, 2019

Informed Consent Form  [PDF] October 17, 2018

More Information

Additional Information:

Link to publication 

Publications of Results:

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: ReveraGen BioPharma, Inc.
• ClinicalTrials.gov Identifier: NCT03038399
• Other Study ID Numbers: VBP15-LTE
• First Posted: January 31, 2017
• Results First Posted: May 20, 2021
• Last Update Posted: May 20, 2021
• Last Verified: April 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by ReveraGen BioPharma, Inc.:

Duchenne muscular dystrophy; vamorolone

Additional relevant MeSH terms:

Muscular Dystrophies; Muscular Dystrophy, Duchenne; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked