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
• Last Update Posted: September 28, 2020
• Sponsor: ReveraGen BioPharma, Inc.
• Collaborators: University of Pittsburgh; Cooperative International Neuromuscular Research Group
• Information provided by (Responsible Party): ReveraGen BioPharma, Inc.

Tracking Information

• First Submitted Date: January 30, 2017
• First Posted Date: January 31, 2017
• Last Update Posted Date: September 28, 2020
• Actual Study Start Date: February 2, 2017
• Actual Primary Completion Date: April 30, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 30, 2017)

• Number of participants with treatment-related adverse events as assessed by CTCAE Version 4.03 [ Time Frame: 24 months ]
• Muscle function measured by Time to Stand Test (TTSTAND) [ Time Frame: 24 weeks ]
• Body size as measured by body mass index (BMI) z-score [ Time Frame: 24 months ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 30, 2017)

• Serum pharmacodynamics biomarkers measured by levels of cortisol [ Time Frame: 24 months ]
• Serum pharmacodynamics biomarkers measured by levels of ACTH [ Time Frame: 24 months ]
• Serum pharmacodynamics biomarkers measured by levels of PINP [ Time Frame: 24 months ]
• Serum pharmacodynamics biomarkers measured by levels of osteocalcin [ Time Frame: 24 months ]
• Serum pharmacodynamics biomarkers measured by levels of CTX [ Time Frame: 24 months ]
• Serum pharmacodynamics biomarkers measured by levels of 17- hydroxyprogesterone [ Time Frame: 24 months ]
• Serum pharmacodynamics biomarkers measured by levels of testosterone [ Time Frame: 24 months ]
• Serum pharmacodynamics biomarkers measured by levels of corticosterone [ Time Frame: 24 months ]
• Serum pharmacodynamics biomarkers measured by levels of 11-deoxycortisol [ Time Frame: 24 months ]
• Serum pharmacodynamics biomarkers measured by levels of glucose [ Time Frame: 24 months ]
• Serum pharmacodynamics biomarkers measured by levels of insulin [ Time Frame: 24 months ]
• Muscle strength measured by Quantitative Muscle Testing (QMT) [ Time Frame: 24 months ]
• Muscle function measured by Time to Climb Test (TTCLIMB) [ Time Frame: 24 months ]
• Muscle function measured by Time to Run/Walk 10 Meters Test (TTRW) [ Time Frame: 24 months ]
• Muscle function measured by North Star Ambulatory Assessment (NSAA) [ Time Frame: 24 months ]
• Muscle function measured by Six-minute Walk Test (6MWT) [ Time Frame: 24 months ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Long-term Extension Study to Assess Vamorolone in Boys With Duchenne Muscular Dystrophy (DMD)
• 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)
• 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.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Duchenne Muscular Dystrophy

Intervention

• Drug: Vamorolone 0.25 mg/day/day
  Oral administration of 0.25 mg/kg/day daily for 24 months.
  Other Name: VBP15
• Drug: Vamorolone 0.75 mg/day/day
  Oral administration of 0.75 mg/kg/day daily for 24 months.
  Other Name: VBP15
• Drug: Vamorolone 2.0 mg/day/day
  Oral administration of 2.0 mg/kg/day daily for 24 months.
  Other Name: VBP15
• Drug: Vamorolone 6.0 mg/day/day
  Oral administration of 6.0 mg/kg/day daily for 24 months.
  Other Name: VBP15

Study Arms

• Experimental: Dose Level Group 1
  Participants enrolled in Dose Level Group 1 will receive vamorolone 0.25 mg/kg/day.
  Intervention: Drug: Vamorolone 0.25 mg/day/day
• Experimental: Dose Level Group 2
  Participants enrolled in Dose Level Group 2 will receive vamorolone 0.75 mg/kg/day.
  Intervention: Drug: Vamorolone 0.75 mg/day/day
• Experimental: Dose Level Group 3
  Participants enrolled in Dose Level Group 3 will receive vamorolone 2.0 mg/kg/day.
  Intervention: Drug: Vamorolone 2.0 mg/day/day
• Experimental: Dose Level Group 4
  Participants enrolled in Dose Level Group 4 will receive vamorolone 6.0 mg/kg/day.
  Intervention: Drug: Vamorolone 6.0 mg/day/day

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 9, 2019): 46
• Original Estimated Enrollment (submitted: January 30, 2017): 48
• Actual Study Completion Date: April 30, 2020
• Actual Primary Completion Date: April 30, 2020 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 4 Years to 7 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, Israel, Sweden, United Kingdom, United States

Administrative Information

• NCT Number: NCT03038399
• Other Study ID Numbers: VBP15-LTE
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

• IPD Sharing Statement: Not Provided
• Responsible Party: ReveraGen BioPharma, Inc.
• Study Sponsor: ReveraGen BioPharma, Inc.

Collaborators

• University of Pittsburgh
• Cooperative International Neuromuscular Research Group

Investigators

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

• PRS Account: ReveraGen BioPharma, Inc.
• Verification Date: September 2020