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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02760264




Registration number
NCT02760264
Ethics application status
Date submitted
28/04/2016
Date registered
3/05/2016
Date last updated
2/01/2019

Titles & IDs
Public title
A Study to Assess Vamorolone in Boys With Duchenne Muscular Dystrophy (DMD)
Scientific title
A Phase IIa Open-Label, Multiple Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Exploratory Efficacy of Vamorolone in Boys With Duchenne Muscular Dystrophy (DMD)
Secondary ID [1] 0 0
1R44NS095423-01
Secondary ID [2] 0 0
VBP15-002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Duchenne Muscular Dystrophy 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Neurological 0 0 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Vamorolone 0.25 mg/kg/day
Treatment: Drugs - Vamorolone 0.75 mg/kg/day
Treatment: Drugs - Vamorolone 2.0 mg/kg/day
Treatment: Drugs - Vamorolone 6.0 mg/kg/day

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

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

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

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


Treatment: Drugs: Vamorolone 0.25 mg/kg/day
Oral administration of 0.25 mg/kg/day daily for 14 days.

Treatment: Drugs: Vamorolone 0.75 mg/kg/day
Oral administration of 0.75 mg/kg/day daily for 14 days.

Treatment: Drugs: Vamorolone 2.0 mg/kg/day
Oral administration of 2.0 mg/kg/day daily for 14 days.

Treatment: Drugs: Vamorolone 6.0 mg/kg/day
Oral administration of 6 mg/kg/day daily for 14 days.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Summary of Adverse Events as Assessed by CTCAE Version 4.03
Timepoint [1] 0 0
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 outcome [1] 0 0
Serum Pharmacodynamic Biomarkers (Insulin Resistance)- Fasting Glucose
Timepoint [1] 0 0
Baseline, Week 2
Secondary outcome [2] 0 0
Serum Pharmacodynamic Biomarkers (Insulin Resistance) -Fasting Glucose
Timepoint [2] 0 0
Baseline, Week 2
Secondary outcome [3] 0 0
Serum Pharmacodynamic Biomarkers (Insulin Resistance)- Insulin
Timepoint [3] 0 0
Baseline , Week 2
Secondary outcome [4] 0 0
Serum Pharmacodynamic Biomarkers (Insulin Resistance)- Insulin
Timepoint [4] 0 0
Baseline, Week 2
Secondary outcome [5] 0 0
Serum Pharmacodynamic Biomarkers (Adrenal Axis Suppression)- First in Morning Cortisol
Timepoint [5] 0 0
Week 2 (pre-dose)
Secondary outcome [6] 0 0
Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin
Timepoint [6] 0 0
Baseline, Day 1, Week 2, Week 4
Secondary outcome [7] 0 0
Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide
Timepoint [7] 0 0
Baseline Day 1 Week 2 Week 4
Secondary outcome [8] 0 0
Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide
Timepoint [8] 0 0
Baseline, Day 1, Week 2, Week 4
Secondary outcome [9] 0 0
Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides
Timepoint [9] 0 0
Baseline, Day 1, Week 4
Secondary outcome [10] 0 0
Pharmacokinetic (PK) Assessments (Tmax)
Timepoint [10] 0 0
Day 1, Week 2
Secondary outcome [11] 0 0
Pharmacokinetic (PK) Assessments (AUC Inf)
Timepoint [11] 0 0
Day 1, Week 2
Secondary outcome [12] 0 0
Pharmacokinetic (PK) Assessments CL (ml/hr/kg)
Timepoint [12] 0 0
Day 1, Week 2
Secondary outcome [13] 0 0
Pharmacokinetic (PK) Assessments t(1/2)
Timepoint [13] 0 0
Day 1, Week 2
Secondary outcome [14] 0 0
Pharmacokinetic (PK) Assessments (Cmax)
Timepoint [14] 0 0
Day 1, Week 2
Secondary outcome [15] 0 0
Metabolites in Safety Testing (MIST) Assessment
Timepoint [15] 0 0
Week 2 (Day 14)

Eligibility
Key inclusion criteria
1. 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;
2. Subject has a confirmed (by Central Genetic Counselor) diagnosis of DMD as defined as:

1. Dystrophin immunofluorescence and/or immunoblot showing complete dystrophin deficiency, and clinical picture consistent with typical DMD, OR
2. 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
3. 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;
3. Subject is = 4 years and < 7 years of age at time of enrollment in the study;
4. Subject is able to complete the Time to Stand Test (TTSTAND) without assistance, as assessed at the Screening and Baseline Visits;
5. 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);
6. 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
7. Subject and parent/guardian are willing and able to comply with scheduled visits, study drug administration plan, and study procedures.
Minimum age
4 Years
Maximum age
6 Years
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
1. Subject has current or history of major renal or hepatic impairment, diabetes mellitus or immunosuppression;
2. Subject has current or history of chronic systemic fungal or viral infections;
3. Subject has had an acute illness within 4 weeks prior to the first dose of study medication;
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 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. 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 taking any other investigational drug currently or has taken any other investigational drug within 3 months prior to the start of study treatment; or
12. Subject has previously been enrolled in the study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/06/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/05/2018
Sample size
Target
Accrual to date
Final
48
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Royal Children's Hospital - Melbourne
Recruitment hospital [2] 0 0
Sydney Children's Hospital - Westmead
Recruitment postcode(s) [1] 0 0
- Melbourne
Recruitment postcode(s) [2] 0 0
- Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
North Carolina
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
Canada
State/province [6] 0 0
Alberta
Country [7] 0 0
Israel
State/province [7] 0 0
Petah Tikvah
Country [8] 0 0
Sweden
State/province [8] 0 0
Gothenburg
Country [9] 0 0
United Kingdom
State/province [9] 0 0
Newcastle upon Tyne

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
ReveraGen BioPharma, Inc.
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
University of Pittsburgh
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Government body
Name [2] 0 0
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Government body
Name [3] 0 0
National Institute of Neurological Disorders and Stroke (NINDS)
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
Cooperative International Neuromuscular Research Group
Address [4] 0 0
Country [4] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT02760264
Trial related presentations / 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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Paula R Clemens, MD
Address 0 0
University of Pittsburgh
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02760264