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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02760277




Registration number
NCT02760277
Ethics application status
Date submitted
28/04/2016
Date registered
3/05/2016
Date last updated
23/07/2019

Titles & IDs
Public title
An Extension Study to Assess Vamorolone in Boys With Duchenne Muscular Dystrophy (DMD)
Scientific 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)
Secondary ID [1] 0 0
1R44NS095423-01
Secondary ID [2] 0 0
VBP15-003
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/day/day
Treatment: Drugs - Vamorolone 0.75 mg/day/day
Treatment: Drugs - Vamorolone 2.0 mg/day/day
Treatment: Drugs - Vamorolone 6.0 mg/day/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/day/day
Oral administration of 0.25 mg/kg/day daily for 24 weeks.

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

Treatment: Drugs: Vamorolone 2.0 mg/day/day
Oral administration of 2.0 mg/kg/day daily for 24 weeks.

Treatment: Drugs: Vamorolone 6.0 mg/day/day
Oral administration of 6.0 mg/kg/day daily for 24 weeks.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Adverse Events as Assessed by CTCAE Version 4.03 - 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). Serious adverse events were recorded for up to 30 days after the final administration of study drug; 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- week Treatment Period, in boys ages 4-7 years with DMD.
Timepoint [1] 0 0
24 weeks
Primary outcome [2] 0 0
Total Number of Adverse Events as Assessed by CTCAE Version 4.03 - 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). Serious adverse events were recorded for up to 30 days after the final administration of study drug; 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- week Treatment Period, in boys ages 4-7 years with DMD.
Timepoint [2] 0 0
24 weeks
Primary outcome [3] 0 0
Muscle Function Measured by Time to Stand Test (TTSTAND)- Velocity - To compare the efficacy, as measured by the Time to Stand Test (TTSTAND), of vamorolone administered orally at daily doses up to 6.0 mg/kg over a 24-week Treatment Period vs. untreated DMD historical controls in boys ages 4-7 years with DMD
Timepoint [3] 0 0
002 Baseline, 003 Baseline, 003 Week 12, Week 24 (Note: 002 Baseline is from VBP15-002 4 week study (NCT02760264), previous to VBP15-003)
Primary outcome [4] 0 0
BMI Z-score - Summary of BMI Z-score of Safety Population.
Please note 0 is the mean. A negative result indicates a response that is many standard deviations below the mean, and a positive result indicates a response that is many standard deviations above the mean. In this case, the closer the group mean BMI Z-score is to 0 is more favorable.
Timepoint [4] 0 0
002 Baseline, 003 Week 12, Week 24
Secondary outcome [1] 0 0
Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c - To investigate the effects of vamorolone, administered orally at daily doses up to 6.0 mg/kg over a 24-week Treatment Period vs. prednisone-treated historical controls, on serum pharmacodynamic (PD) biomarkers of safety (insulin resistance, adrenal axis suppression, and bone turnover). SomaScan aptamer panels testing 1,200 serum proteins were used to discover a candidate set of prednisone-responsive biomarkers, with a subset of these validating in a longitudinal sample set (individual DMD patients pre/post steroid treatment). These PD biomarkers were assigned to a safety panel or efficacy panel based on comparison to normal controls and information concerning the function of each protein.
Timepoint [1] 0 0
002 Baseline, 003 Week 8, 003 Week 16, 003 Week 24, 003 Week 26-29
Secondary outcome [2] 0 0
Serum Pharmacodynamics Biomarkers Measured by Levels of ACTH - To investigate the effects of vamorolone, administered orally at daily doses up to 6.0 mg/kg over a 24-week Treatment Period vs. prednisone-treated historical controls, on serum pharmacodynamic (PD) biomarkers of safety (insulin resistance, adrenal axis suppression, and bone turnover). SomaScan aptamer panels testing 1,200 serum proteins were used to discover a candidate set of prednisone-responsive biomarkers, with a subset of these validating in a longitudinal sample set (individual DMD patients pre/post steroid treatment). These PD biomarkers were assigned to a safety panel or efficacy panel based on comparison to normal controls and information concerning the function of each protein.
Timepoint [2] 0 0
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)
Secondary outcome [3] 0 0
Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Glucose - To investigate the effects of vamorolone, administered orally at daily doses up to 6.0 mg/kg over a 24-week Treatment Period vs. prednisone-treated historical controls, on serum pharmacodynamic (PD) biomarkers of safety (insulin resistance, adrenal axis suppression, and bone turnover). SomaScan aptamer panels testing 1,200 serum proteins were used to discover a candidate set of prednisone-responsive biomarkers, with a subset of these validating in a longitudinal sample set (individual DMD patients pre/post steroid treatment). These PD biomarkers were assigned to a safety panel or efficacy panel based on comparison to normal controls and information concerning the function of each protein.
Timepoint [3] 0 0
002 Baseline, 003 Week 12, 003 Week 24
Secondary outcome [4] 0 0
Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Insulin - To investigate the effects of vamorolone, administered orally at daily doses up to 6.0 mg/kg over a 24-week Treatment Period vs. prednisone-treated historical controls, on serum pharmacodynamic (PD) biomarkers of safety (insulin resistance, adrenal axis suppression, and bone turnover). SomaScan aptamer panels testing 1,200 serum proteins were used to discover a candidate set of prednisone-responsive biomarkers, with a subset of these validating in a longitudinal sample set (individual DMD patients pre/post steroid treatment). These PD biomarkers were assigned to a safety panel or efficacy panel based on comparison to normal controls and information concerning the function of each protein.
Timepoint [4] 0 0
002 Baseline, 003 Week 12, 003 Week 24
Secondary outcome [5] 0 0
Serum Pharmacodynamics Biomarkers Measured by Levels of Osteocalcin - To investigate the effects of vamorolone, administered orally at daily doses up to 6.0 mg/kg over a 24-week Treatment Period vs. prednisone-treated historical controls, on serum pharmacodynamic (PD) biomarkers of safety (insulin resistance, adrenal axis suppression, and bone turnover). SomaScan aptamer panels testing 1,200 serum proteins were used to discover a candidate set of prednisone-responsive biomarkers, with a subset of these validating in a longitudinal sample set (individual DMD patients pre/post steroid treatment). These PD biomarkers were assigned to a safety panel or efficacy panel based on comparison to normal controls and information concerning the function of each protein.
Timepoint [5] 0 0
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)
Secondary outcome [6] 0 0
Serum Pharmacodynamics Biomarkers Measured by Levels of P1NP - To investigate the effects of vamorolone, administered orally at daily doses up to 6.0 mg/kg over a 24-week Treatment Period vs. prednisone-treated historical controls, on serum pharmacodynamic (PD) biomarkers of safety (insulin resistance, adrenal axis suppression, and bone turnover). SomaScan aptamer panels testing 1,200 serum proteins were used to discover a candidate set of prednisone-responsive biomarkers, with a subset of these validating in a longitudinal sample set (individual DMD patients pre/post steroid treatment). These PD biomarkers were assigned to a safety panel or efficacy panel based on comparison to normal controls and information concerning the function of each protein.
Timepoint [6] 0 0
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)
Secondary outcome [7] 0 0
Serum Pharmacodynamics Biomarkers Measured by Levels of CTX - To investigate the effects of vamorolone, administered orally at daily doses up to 6.0 mg/kg over a 24-week Treatment Period vs. prednisone-treated historical controls, on serum pharmacodynamic (PD) biomarkers of safety (insulin resistance, adrenal axis suppression, and bone turnover). SomaScan aptamer panels testing 1,200 serum proteins were used to discover a candidate set of prednisone-responsive biomarkers, with a subset of these validating in a longitudinal sample set (individual DMD patients pre/post steroid treatment). These PD biomarkers were assigned to a safety panel or efficacy panel based on comparison to normal controls and information concerning the function of each protein.
Timepoint [7] 0 0
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)
Secondary outcome [8] 0 0
Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Climb Test (TTCLIMB)- Velocity - To investigate the effects of vamorolone, administered orally at daily doses up to 6.0 mg/kg over a 24-week Treatment Period, on muscle strength, mobility and functional exercise capacity vs. historical controls as measured by Time to Climb Test (TTCLIMB) in boys ages 4-7 years with DMD.
Timepoint [8] 0 0
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)
Secondary outcome [9] 0 0
Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Run/Walk 10 Meters Test (TTRW)- Velocity - To investigate the effects of vamorolone, administered orally at daily doses up to 6.0 mg/kg over a 24-week Treatment Period, on muscle strength, mobility and functional exercise capacity vs. historical controls as measured by Time to Run/Walk Test (TTRW) in boys ages 4-7 years with DMD.
Timepoint [9] 0 0
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)
Secondary outcome [10] 0 0
Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by North Star Ambulatory Assessment (NSAA) - To investigate the effects of vamorolone, administered orally at daily doses up to 6.0 mg/kg over a 24-week Treatment Period, on muscle strength, mobility and functional exercise capacity vs. historical controls as measured by North Star Ambulatory Assessment (NSAA) in boys ages 4-7 years with DMD. ***Total NSAA score is being reported. The score can range from 0 to 32. Higher scores (approaching 32) indicate a better outcome assessing functional mobility.
Timepoint [10] 0 0
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)
Secondary outcome [11] 0 0
Muscle Strength, Mobility, and Functional Exercise Capacity vs. Historical Controls as Measured by 6-minute Walk Test (6MWT) Meters - To investigate the effects of vamorolone, administered orally at daily doses up to 6.0 mg/kg over a 24-week Treatment Period, on muscle strength, mobility and functional exercise capacity vs. historical controls as measured by 6-minute Walk Test (6MWT) in boys ages 4-7 years with DMD.
Timepoint [11] 0 0
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)

Eligibility
Key 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.
Minimum age
4 Years
Maximum age
7 Years
Gender
Males
Can healthy volunteers participate?
No
Key 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

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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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 Tikwah
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 Neurological Disorders and Stroke (NINDS)
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Cooperative International Neuromuscular Research Group
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Government body
Name [4] 0 0
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Address [4] 0 0
Country [4] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02760277
Trial related presentations / publications
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
Other publications