An Extension Study to Assess the Long-term Safety and Efficacy of Vamorolone in Boys With Duchenne Muscular Dystrophy (DMD)

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2016-004263-38-GB
• Date of registration: 08/02/2019
• Prospective Registration: No
• Primary sponsor: ReveraGen BioPharma, Inc.
• Public title: An Extension Study to Assess the Long-term Safety and Efficacy of Vamorolone in Boys With Duchenne Muscular Dystrophy (DMD)
• Scientific title: A Phase II Open-label, Multicenter Extension Study to Assess the Longterm Safety and Efficacy of Vamorolone in Boys with Duchenne Muscular Dystrophy (DMD)
• Date of first enrolment: 10/02/2017
• Target sample size: 48
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-004263-38
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: yes Other trial design description: Multiple ascending dose If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Canada, Israel, Sweden, United Kingdom, United States

Contacts

• Name: Jesse Damsker
• Affiliation: ReveraGen BioPharma Inc

• Name: Jesse Damsker
• Affiliation: ReveraGen BioPharma Inc

Key inclusion & exclusion criteria

Inclusion criteria:
1. Subject's parent or legal guardian has provided written informed
consent/HIPAA authorization prior to any extension study-specific
procedures;
2. Subject has previously completed study VBP15-002 up to and
including the Week 4 Follow-up assessments within 8 weeks prior to
enrollment; and
3. Subject and parent/guardian are willing and able to comply with
scheduled visits, study drug administration plan, and study procedures.
Are the trial subjects under 18? yes
Number of subjects for this age range: 48
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Subject 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. 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 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; or
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.



Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

Duchenne muscular dystrophy (DMD)
MedDRA version: 20.0 Level: PT Classification code 10013801 Term: Duchenne muscular dystrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Intervention(s)

Product Name: Vamarolone
Product Code: VBP15
Pharmaceutical Form: Oral suspension
INN or Proposed INN: vamorolone
CAS Number: 13209-41-1
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: equal
Concentration number: 0.25-

Product Name: Vamorolone
Product Code: VBP15
Pharmaceutical Form: Oral suspension
INN or Proposed INN: vamorolone
CAS Number: 13209-41-1
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: equal
Concentration number: 0.75-

Product Name: Vamorolone
Product Code: VBP15
Pharmaceutical Form: Oral suspension
INN or Proposed INN: vamorolone
CAS Number: 13209-41-1
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: equal
Concentration number: 2.0-

Product Name: Vamorolone
Product Code: VBP15
Pharmaceutical Form: Oral suspension
INN or Proposed INN: vamorolone
CAS Number: 13209-41-1
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: equal
Concentration number: 6.0-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: See E.5.1

Primary end point(s): Safety Endpoint
- BMI z-score: Comparison with a prednisone-treated historical control
group for change from Baseline to Week 24.
Clinical Efficacy Endpoint
- Time to Stand Test (TTSTAND) velocity (rise/second): Comparison with
a historical natural history (untreated) control group for change from
Baseline to Week 24.

Main Objective: The primary objectives:
1. To evaluate the long-term safety and tolerability of vamorolone,
administered orally at daily doses up to 6.0 mg/kg over a 24-week
Treatment Period, in boys ages 4-7 years with DMD;
2. 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; and
3. To compare the safety, as measured by body mass index (BMI) zscore,
of vamorolone administered orally at daily doses up to 6.0 mg/kg
over a 24-week Treatment Period vs. prednisone-treated historical
controls in boys ages 4-7 years with DMD.

Secondary Objective: 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);
- vs. untreated historical controls, on serum PD biomarkers of efficacy
(inflammatory protein suppression); and
- on muscle strength, mobility and functional exercise capacity vs.
historical controls as measured by Quantitative Muscle Testing (QMT),
Time to Run/Walk Test (TTRW), North Star Ambulatory Assessment
(NSAA), Time to Climb Test (TTCLIMB), and 6-minute Walk Test (6MWT)
in boys ages 4-7 years with DMD.
Exploratory Objective: To investigate the effects of vamorolone
administered orally at daily doses up to 6.0 mg/kg over a 24-week
Treatment Period on an extended panel of PD biomarkers using
SomaScan aptamer arrays, and proteomic profiling.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: See E.5.2

Secondary end point(s): Safety Endpoints
1. BMI z-score: Change from Baseline to each of the scheduled ontreatment and post treatment assessment time points.
2. Treatment-emergent adverse events (TEAEs) and serious adverse
events (SAEs) by system organ class (SOC): Overall by treatment, by
treatment and relationship, and by treatment and intensity.;
3. Vital signs [blood pressure, heart rate, respiratory rate, body
temperature]: Change from Baseline to each of the scheduled on treatment and post-treatment assessment time points;
4. Body weight: Change from Baseline to each of the scheduled on treatmentand post-treatment assessment time points;
5. Clinical laboratory values (hematology and biochemistry): Change
from Baseline to each of the scheduled on-treatment and post-treatment assessment time points;
6. Lipid profile (triglycerides, total cholesterol, low density lipoprotein [LDL], high density lipoprotein [HDL]): Change from Baseline to each of the scheduled on-treatment and post-treatment assessment time points;
7. Urinalysis by dipstick and microscopic analysis: Change from Baseline to each of the scheduled on-treatment and post-treatment assessment time points;
8. 12-lead electrocardiogram (ECG): Change from Baseline to each of the scheduled on-treatment and post-treatment assessment time points Efficacy Endpoints
1. Time to Stand Test (TTSTAND) velocity (rise/second): Change from
Baseline to each of the scheduled on-treatment and post-treatment
assessment time points;
2. Time to Climb (4 Steps) Test (TTCLIMB): Change from Baseline to
each of the scheduled on-treatment and post-treatment assessment time points;
3. North Star Ambulatory Assessment (NSAA): Change in timed
assessments and total score from Baseline to each of the scheduled on treatment and post-treatment assessment time points;
4. Quantitative Muscle Testing (QMT): Change from Baseline to each of the scheduled on-treatment and post-treatment assessment time points;
5. Total distance traveled, in meters, in completing the Six-minute Walk Test (6MWT): Change from Baseline to each of the scheduled ontreatment and post-treatment assessment time points; and
6. Time to Run/Walk Test (TTRW): Change from Baseline to each of the scheduled on-treatment and post-treatment assessment time points.
Pharmacodynamic Endpoints
1. Concentrations of serum PD biomarkers: osteocalcin, ACTH, insulin, glucose, 17 hydroxyprogesterone, carboxy-terminal telopeptide (CTX), serum aminoterminal propeptide of type I collagen (P1NP), cortisol, testosterone, corticosterone, 11-deoxycortisol, and hemoglobin A1c (HbA1c).
Exploratory Endpoints
- Levels of an extended panel of PD biomarkers using SomaScan aptamer arrays and proteomic profiling.
Acceptability of vamorolone by a 5-point hedonic scale at the Week 12 and Week 24 Visits.
Quality of life assessment by Pediatric Outcomes Data Collection
Instrument at Baseline Day -1, Week 12, and Week 24 Visits.

Secondary ID(s)

VBP15-003

2016-004263-38-SE

NCT02760264

Source(s) of Monetary Support

ReveraGen BioPharma, Inc.

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 30/03/2019
• Date Completed: 26/04/2018
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-004263-38/results