Clinical trial NCT02760277: An Extension Study to Assess Vamorolone in Boys With Duchenne Muscular Dystrophy (DMD)
Official title: A Phase II Open-label, Multicenter Extension Study to Assess the Long-term Safety and Efficacy of Vamorolone in Boys With Duchenne Muscular Dystrophy (DMD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Duchenne Muscular Dystrophy
Keywords: Duchenne muscular dystrophy
vamorolone
Lead sponsor: ReveraGen BioPharma, Inc.
Sponsor class: INDUSTRY
Collaborators: name: University of Pittsburgh
name: National Institute of Neurological Disorders and Stroke (NINDS)
name: Cooperative International Neuromuscular Research Group
name: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
First posted: 2016-05-03
Enrollment: 48
Sex: MALE
Minimum age (years): 4
Maximum age (years): 7
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The main purposes of this study are to see if it is safe to use a new medication called vamorolone for more than two weeks in children with Duchenne muscular dystrophy (DMD), to see if vamorolone works for the treatment for DMD, and to see how any potential side effects compare to those seen in boys using steroids.

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 weeks.

Eligibility criteria: Inclusion Criteria:

1. Participant's parent or legal guardian has provided written informed consent/HIPAA authorization prior to any extension study-specific procedures;
2. Participant has previously completed study VBP15-002 up to and including the Week 4 Follow-up assessments within 8 weeks prior to enrollment; and
3. Participant and parent/guardian are willing and able to comply with scheduled visits, study drug administration plan, and study procedures.

Exclusion Criteria:

1. Participant had a serious or severe adverse event in study VBP15-002 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 study;
2. Participant has current or history of major renal or hepatic impairment, diabetes mellitus or immunosuppression;
3. Participant has current or history of chronic systemic fungal or viral infections;
4. Participant 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. Participant has evidence of symptomatic cardiomyopathy. \[Note: Asymptomatic cardiac abnormality on investigation would not be exclusionary\];
6. Participant is currently being treated or has received previous treatment with oral glucocorticoids or other immunosuppressive agents. \[Notes: Past transient use of oral glucocorticoids or other oral immunosuppressive agents for no longer than 3 months cumulative, with last use at least 3 months prior to first dose of study medication, will be considered for eligibility on a case-by-case basis. Inhaled and/or topical corticosteroids prescribed for an indication other than DMD are permitted but must be administered at stable dose for at least 3 months prior to study drug administration\];
7. Subject has used idebenone within 4 weeks prior to the first dose of study medication;
8. Participant has an allergy or hypersensitivity to the study medication or to any of its constituents;
9. Participant has severe behavioral or cognitive problems that preclude participation in the study, in the opinion of the Investigator;
10. Participant 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; or
11. Participant 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: Participants may be re-evaluated if ineligible due to a transient condition which would prevent the subject from participating

Primary outcomes:
measure: Number of Participants With Adverse Events as Assessed by CTCAE Version 4.03
timeFrame: 24 weeks
measure: Total Number of Adverse Events as Assessed by CTCAE Version 4.03
timeFrame: 24 weeks
measure: Muscle Function Measured by Time to Stand Test (TTSTAND)- Velocity
timeFrame: 002 Baseline, 003 Baseline, 003 Week 12, Week 24 (Note: 002 Baseline is from VBP15-002 4 week study (NCT02760264), previous to VBP15-003)
measure: BMI Z-score
timeFrame: 002 Baseline, 003 Week 12, Week 24
Secondary outcomes:
measure: Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c
timeFrame: 002 Baseline, 003 Week 8, 003 Week 16, 003 Week 24, 003 Week 26-29
measure: Serum Pharmacodynamics Biomarkers Measured by Levels of ACTH
timeFrame: 002 Baseline, 003 Baseline, 003 Week 8, 003 Week 16, 003 Week 24, 003 Week 26-29 (Note: 002 Baseline is from VBP15-002 4 week study (NCT02760264), previous to VBP15-003)
measure: Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Glucose
timeFrame: 002 Baseline, 003 Week 12, 003 Week 24
measure: Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Insulin
timeFrame: 002 Baseline, 003 Week 12, 003 Week 24
measure: Serum Pharmacodynamics Biomarkers Measured by Levels of Osteocalcin
timeFrame: 002 Baseline, 003 Baseline, 003 Week 8, 003 Week 16, 003 Week 24, 003 Week 26-29 (Note: 002 Baseline is from VBP15-002 4 week study (NCT02760264), previous to VBP15-003)
measure: Serum Pharmacodynamics Biomarkers Measured by Levels of P1NP
timeFrame: 002 Baseline, 003 Baseline, 003 Week 8, 003 Week 16, 003 Week 24, 003 Week 26-29 (Note: 002 Baseline is from VBP15-002 4 week study (NCT02760264), previous to VBP15-003)
measure: Serum Pharmacodynamics Biomarkers Measured by Levels of CTX
timeFrame: 002 Baseline, 003 Baseline, 003 Week 8, 003 Week 16, Week 24, 003 Week 26-29 (Note: 002 Baseline is from VBP15-002 4 week study (NCT02760264), previous to VBP15-003)
measure: Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Climb Test (TTCLIMB)- Velocity
timeFrame: 002 Baseline, 003 Baseline, 003 Week 12, 003 Week 24 (Note: 002 Baseline is from VBP15-002 4 week study (NCT02760264), previous to VBP15-003)
measure: Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Run/Walk 10 Meters Test (TTRW)- Velocity
timeFrame: 002 Baseline, 003 Baseline, 003 Week 12, 003 Week 24 (Note: 002 Baseline is from VBP15-002 4 week study (NCT02760264), previous to VBP15-003)
measure: Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by North Star Ambulatory Assessment (NSAA)
timeFrame: 002 Baseline, 003 Baseline, 003 Week 12, 003 Week 24 (Note: 002 Baseline is from VBP15-002 4 week study (NCT02760264), previous to VBP15-003)
measure: Muscle Strength, Mobility, and Functional Exercise Capacity vs. Historical Controls as Measured by 6-minute Walk Test (6MWT) Meters
timeFrame: 002 Baseline, 003 Baseline, 003 Week 12, 003 Week 24 (Note: 002 Baseline is from VBP15-002 4 week study (NCT02760264), previous to VBP15-003)
Other outcomes:
Locations:
city: Davis
country: United States
facility: University of California Davis
state: California
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Orlando
country: United States
facility: Nemours Children's Hospital
state: Florida
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital
state: Illinois
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Melbourne
country: Australia
facility: Royal Children's Hospital
city: Westmead
country: Australia
facility: Sydney Children's Hospital
city: Calgary
country: Canada
facility: Alberta Children's Hospital
state: Alberta
city: Petah Tikwah
country: Israel
facility: Schneider Children's Medical Center
city: Gothenburg
country: Sweden
facility: Queen Silvia Children's Hospital
city: Newcastle upon Tyne
country: United Kingdom
facility: Newcastle upon Tyne Hospitals NHS Foundation Trust
Study officials:
affiliation: University of Pittsburgh
name: Paula R Clemens, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.