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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03439670




Registration number
NCT03439670
Ethics application status
Date submitted
9/01/2018
Date registered
20/02/2018
Date last updated
9/03/2023

Titles & IDs
Public title
A Study to Assess the Efficacy and Safety of Vamorolone in Boys With Duchenne Muscular Dystrophy (DMD)
Scientific title
A Phase IIb Randomized, Double-blind, Parallel Group, Placebo- and Active-controlled Study With Double-Blind Extension to Assess the Efficacy and Safety of Vamorolone in Ambulant Boys With Duchenne Muscular Dystrophy (DMD)
Secondary ID [1] 0 0
VBP15-004
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
Treatment: Drugs - Prednisone
Other interventions - Placebo
Treatment: Drugs - Vamorolone
Treatment: Drugs - Prednisone
Other interventions - Placebo
Treatment: Drugs - Vamorolone
Treatment: Drugs - Vamorolone

Experimental: Treatment Group 1 - Patients enrolled in Treatment Group 1 (experimental group) will receive vamorolone 2.0 mg/kg/day for the duration of the study.

Experimental: Treatment Group 2 - Patients enrolled in Treatment Group 2 (experimental group) will receive vamorolone at 6.0 mg/kg/day for the duration of the study.

Active comparator: Treatment Group 3 - Patients enrolled in Treatment Group 3 (active comparator group) will receive prednisone 0.75 mg/kg/day for 24 weeks followed by 20 weeks of treatment with 2.0 mg/kg/day vamorolone.

Active comparator: Treatment Group 4 - Patients enrolled in Treatment Group 4 (active comparator group) will receive prednisone 0.75 mg/kg/day for 24 weeks followed by 20 weeks treatment with 6.0 mg/kg/day vamorolone.

Placebo comparator: Treatment Group 5 - Patients enrolled in Treatment Group 5 (placebo comparator group) will receive placebo daily for 24 weeks followed by 20 weeks treatment with 2.0 mg/kg/day vamorolone.

Placebo comparator: Treatment Group 6 - Patients enrolled in Treatment Group 6 (placebo comparator group) will receive placebo daily for 24 weeks followed by 20 weeks treatment with 6.0 mg/kg/day vamorolone.


Treatment: Drugs: Vamorolone
Oral administration of 2.0 mg/kg/day for the duration of the study.

Treatment: Drugs: Prednisone
Oral administration of 0.75 mg/kg/day for 24 weeks.

Other interventions: Placebo
Oral administration of placebo daily for 24 weeks.

Treatment: Drugs: Vamorolone
Oral administration of 6.0 mg/kg/day for the duration of the study.

Treatment: Drugs: Prednisone
Oral administration of 0.75 mg/kg/day for 24 weeks.

Other interventions: Placebo
Oral administration of placebo daily for 24 weeks.

Treatment: Drugs: Vamorolone
Oral administration of 2.0 mg/kg/day for 20 weeks.

Treatment: Drugs: Vamorolone
Oral administration of 6.0 mg/kg/day for 20 weeks.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Efficacy Measured by Time to Stand Test (TTSTAND) Velocity in Rises/Second Change From Baseline
Timepoint [1] 0 0
24 weeks

Eligibility
Key inclusion criteria
1. Subject's parent(s) or legal guardian(s) has (have) provided written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization, where applicable, prior to any study-related procedures; participants will be asked to give written or verbal assent according to local requirements
2. Subject has a centrally confirmed (by TRiNDS central genetic counselor[s]) diagnosis of DMD as defined as:

* Dystrophin immunofluorescence and/or immunoblot showing complete dystrophin deficiency, and clinical picture consistent with typical DMD, OR
* 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
* 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 clinical picture consistent with typical DMD;
3. Subject is = 4 years and <7 years of age at time of enrollment in the study;
4. Subject weighs >13.0 kg and = 39.9 kg at the Screening Visit;
5. Subject is able to walk independently without assistive devices;
6. Subject is able to complete the Time to Stand Test (TTSTAND) without assistance in <10 seconds, as assessed at the Screening Visit;
7. 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. [Notes: Serum gamma glutamyl transferase (GGT), creatinine, and total bilirubin all must be = upper limit of the normal range at the Screening Visit. An abnormal vitamin D level that is considered clinically significant will not exclude a subject from randomization];
8. 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 local laboratory from blood collected during the Screening Period, OR
* Documentation, provided at the Screening Visit, that the subject has had 2 doses of varicella vaccine, with or without serologic evidence of immunity; the second of the 2 immunizations must have been given at least 14 days prior to randomization.
9. Subject is able to swallow tablets, as confirmed by successful test swallowing of placebo tablets during the Screening Period; and
10. Subject and parent(s)/guardian(s) are willing and able to comply with scheduled visits, study drug administration plan, and study procedures.
Minimum age
4 Years
Maximum age
7 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 a history of primary hyperaldosteronism;
6. Subject has evidence of symptomatic cardiomyopathy [Note: Asymptomatic cardiac abnormality on investigation would not be exclusionary];
7. 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 1 month 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, unless discontinued for intolerance. Inhaled and/or topical glucocorticoids are permitted if last use is at least 4 weeks prior to first dose of study medication or if administered at stable dose beginning at least 4 weeks prior to first dose of study medication and anticipated to be used at the stable dose regimen for the duration of the study];
8. Subject has an allergy or hypersensitivity to the study medication or to any of its constituents;
9. Subject has used idebenone within 4 weeks prior to the first dose of study medication;
10. Subject has severe behavioral or cognitive problems that preclude participation in the study, in the opinion of the Investigator;
11. 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;
12. Subject is taking (or has taken within 4 weeks prior to the first dose of study medication) herbal remedies and supplements which can impact muscle strength and function (e.g., Co-enzyme Q10, creatine, etc);
13. Subject is taking (or has taken within 3 months prior to the first dose of study medication) any medication indicated for DMD, including Exondys51 and Translarna;
14. Subject has been administered a live attenuated vaccine within 14 days prior to the first dose of study medication;
15. Subject is currently taking any other investigational drug or has taken any other investigational drug within 3 months prior to the first dose of study medication;
16. Subject has a sibling who is currently enrolled in any vamorolone study or Expanded Access Program, or who intends to enroll in any vamorolone study or Expanded Access Program during the subject's participation in the VBP15-004 study; or
17. Subject has previously been enrolled in the study. Note: Any parameter/test may be repeated at the Investigator's discretion during Screening to determine reproducibility. In addition, subjects may be rescreened if ineligible due to a transient condition which would prevent the subject from participating, such as an upper respiratory tract infection or injury, or if ineligible due to negative anti-varicella IgG antibody test result.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
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
29/06/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
19/08/2021
Sample size
Target
Accrual to date
Final
121
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
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Minnesota
Country [6] 0 0
United States of America
State/province [6] 0 0
North Carolina
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
United States of America
State/province [8] 0 0
Virginia
Country [9] 0 0
United States of America
State/province [9] 0 0
Washington
Country [10] 0 0
Belgium
State/province [10] 0 0
Ghent
Country [11] 0 0
Belgium
State/province [11] 0 0
Leuven
Country [12] 0 0
Canada
State/province [12] 0 0
Alberta
Country [13] 0 0
Canada
State/province [13] 0 0
British Columbia
Country [14] 0 0
Canada
State/province [14] 0 0
Ontario
Country [15] 0 0
Canada
State/province [15] 0 0
Quebec
Country [16] 0 0
Czechia
State/province [16] 0 0
Brno
Country [17] 0 0
Czechia
State/province [17] 0 0
Prague
Country [18] 0 0
Greece
State/province [18] 0 0
Athens
Country [19] 0 0
Israel
State/province [19] 0 0
Petah Tikvah
Country [20] 0 0
Netherlands
State/province [20] 0 0
Leiden
Country [21] 0 0
Netherlands
State/province [21] 0 0
Nijmegen
Country [22] 0 0
Spain
State/province [22] 0 0
Barcelona
Country [23] 0 0
Spain
State/province [23] 0 0
Valencia
Country [24] 0 0
Sweden
State/province [24] 0 0
Gothenburg
Country [25] 0 0
United Kingdom
State/province [25] 0 0
Birmingham
Country [26] 0 0
United Kingdom
State/province [26] 0 0
Glasgow
Country [27] 0 0
United Kingdom
State/province [27] 0 0
Leeds
Country [28] 0 0
United Kingdom
State/province [28] 0 0
Liverpool
Country [29] 0 0
United Kingdom
State/province [29] 0 0
London
Country [30] 0 0
United Kingdom
State/province [30] 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
European Union
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Cooperative International Neuromuscular Research Group
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Newcastle University
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
University of Pittsburgh
Address [4] 0 0
Country [4] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Brief Summary: This Phase IIb study is a randomized, double-blind, parallel group, placebo and active-controlled study to evaluate the efficacy, safety, PD, and population PK of vamorolone administered orally at daily doses of 2.0 mg/kg and 6.0 mg/kg versus prednisone 0.75 mg/kg/day and placebo over a Treatment Period of 24 weeks, and to evaluate persistence of effect over a Treatment Period of 48 weeks in ambulant boys ages 4 to \<7 years with DMD.
Trial website
https://clinicaltrials.gov/study/NCT03439670
Trial related presentations / publications
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McDonald CM, Henricson EK, Abresch RT, Han JJ, Escolar DM, Florence JM, Duong T, Arrieta A, Clemens PR, Hoffman EP, Cnaan A; Cinrg Investigators. The cooperative international neuromuscular research group Duchenne natural history study--a longitudinal investigation in the era of glucocorticoid therapy: design of protocol and the methods used. Muscle Nerve. 2013 Jul;48(1):32-54. doi: 10.1002/mus.23807. Epub 2013 May 16.
Henricson EK, Abresch RT, Cnaan A, Hu F, Duong T, Arrieta A, Han J, Escolar DM, Florence JM, Clemens PR, Hoffman EP, McDonald CM; CINRG Investigators. The cooperative international neuromuscular research group Duchenne natural history study: glucocorticoid treatment preserves clinically meaningful functional milestones and reduces rate of disease progression as measured by manual muscle testing and other commonly used clinical trial outcome measures. Muscle Nerve. 2013 Jul;48(1):55-67. doi: 10.1002/mus.23808. Epub 2013 May 6.
Escolar DM, Hache LP, Clemens PR, Cnaan A, McDonald CM, Viswanathan V, Kornberg AJ, Bertorini TE, Nevo Y, Lotze T, Pestronk A, Ryan MM, Monasterio E, Day JW, Zimmerman A, Arrieta A, Henricson E, Mayhew J, Florence J, Hu F, Connolly AM. Randomized, blinded trial of weekend vs daily prednisone in Duchenne muscular dystrophy. Neurology. 2011 Aug 2;77(5):444-52. doi: 10.1212/WNL.0b013e318227b164. Epub 2011 Jul 13.
Guglieri M, Clemens PR, Perlman SJ, Smith EC, Horrocks I, Finkel RS, Mah JK, Deconinck N, Goemans N, Haberlova J, Straub V, Mengle-Gaw LJ, Schwartz BD, Harper AD, Shieh PB, De Waele L, Castro D, Yang ML, Ryan MM, McDonald CM, Tulinius M, Webster R, McMillan HJ, Kuntz NL, Rao VK, Baranello G, Spinty S, Childs AM, Sbrocchi AM, Selby KA, Monduy M, Nevo Y, Vilchez-Padilla JJ, Nascimento-Osorio A, Niks EH, de Groot IJM, Katsalouli M, James MK, van den Anker J, Damsker JM, Ahmet A, Ward LM, Jaros M, Shale P, Dang UJ, Hoffman EP. Efficacy and Safety of Vamorolone vs Placebo and Prednisone Among Boys With Duchenne Muscular Dystrophy: A Randomized Clinical Trial. JAMA Neurol. 2022 Oct 1;79(10):1005-1014. doi: 10.1001/jamaneurol.2022.2480.
Public notes

Contacts
Principal investigator
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Michela Guglieri, M.D.
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John Walton Muscular Dystrophy Research Centre
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Contact person for public queries
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Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03439670