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: 14 December 2020
• Main ID: EUCTR2017-003568-10-GB
• Date of registration: 17/05/2018
• 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 24-month Phase II Open-label, Multicenter Long-term Extension Study to Assess the Long-term Safety and Efficacy of Vamorolone in Boys with Duchenne Muscular Dystrophy (DMD) - VBP15-LTE
• Date of first enrolment: 05/01/2018
• Target sample size: 48
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-003568-10
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: no; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; 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: Director, Research
• Affiliation: ReveraGen BioPharma Inc.

• Name: Director, Research
• Affiliation: ReveraGen BioPharma Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Subject's parent or legal guardian has provided written informed consent and HIPAA authorization (if applicable) prior to any VBP15-LTE longterm extension study-specific procedures;
2. Subject has previously completed study VBP15-003 up to and including the Week 24 Final assessments, prior to enrolling in the VBP15-LTE study at the conclusion of the VBP15-003 Week 24 Visit [Note: if entering the dose-tapering period, subject is enrolling within 8 weeks after the VBP15-003 final visit following dose-tapering]; 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: 7
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion criteria:
1. Subject had a serious or severe adverse event in study VBP15-003 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 long-term extension 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 glucocorticoids 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 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: Vamorolone
Pharmaceutical Form: Oral suspension
INN or Proposed INN: Vamorolone
CAS Number: 13209-41-1
Other descriptive name: EV substance code: SUB188638
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 40-

Product Name: Vamorolone
Pharmaceutical Form: Oral suspension
INN or Proposed INN: Vamorolone
CAS Number: 13209-41-1
Other descriptive name: EV substance code: SUB188638
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 40-

Product Name: Vamorolone
Pharmaceutical Form: Oral suspension
INN or Proposed INN: Vamorolone
CAS Number: 13209-41-1
Other descriptive name: EV substance code: SUB188638
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 40-

Product Name: Vamorolone
Pharmaceutical Form: Oral suspension
INN or Proposed INN: Vamorolone
CAS Number: 13209-41-1
Other descriptive name: EV substance code: SUB188638
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 40-

Primary Outcome(s)

Primary end point(s): Safety Endpoint BMI z-score: Comparison with a prednisone-treated historical control group for change from Baseline to Month 12.

Efficacy Endpoint Time to Stand Test (TTSTAND) velocity (rise/second): Comparison with a historical natural history (untreated) control group for change from Baseline to Month 12.

Main Objective: Primary: 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-month Treatment Period, in young boys with DMD who completed protocol VBP15-003; 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-month Treatment Period vs. untreated DMD historical controls in young boys with DMD; and 3. To compare the safety, as measured by body mass index (BMI) z-score, of vamorolone administered orally at daily doses up to 6.0 mg/kg over a 24-month Treatment Period vs. prednisone-treated historical controls in young boys with DMD.

Secondary Objective: To investigate the effects of vamorolone, administered orally at daily doses up to 6.0 mg/kg over a 24-month Treatment Period:
- vs. prednisone-treated historical controls, on serum pharmacodynamic (PD) biomarkers of safety (insulin resistance, adrenal axis suppression, and bone turnover); and
-on muscle strength, mobility and functional exercise capacity vs. untreated DMD historical controls as measured by Time to Run/Walk Test (TTRW), North Star Ambulatory Assessment (NSAA), Time to Climb Test (TTCLIMB), 6-minute Walk Test (6MWT), and Quantitative Muscle Testing (QMT) in young boys with DMD.
Exploratory Objectives To investigate the effects of vamorolone administered orally at daily doses up to 6.0 mg/kg over a 24-month Treatment Period on:

-Quality of Life measures (Peadiatric Outcomes Data Collection Instrument [PODCI]); and

-on an extended panel of exploratory PD biomarkers using somaSCAN aptamer arrays, steroid hormone profiling, and other biomarker methods.

Timepoint(s) of evaluation of this end point: Baseline, Month 12

Secondary Outcome(s)

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, oral body temperature]: Change from Baseline to each of the scheduled ontreatment and post-treatment assessment time points;
4. Body weight: Change from Baseline to each of the scheduled ontreatment and 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; Data for the following additional safety outcomes will be listed only: Physical examination findings at Pretreatment, Month 12, and Month 24.

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 ontreatment and post-treatment assessment time points;
4. Total distance traveled, in meters, in completing the Six-minute Walk Test (6MWT): Change from Baseline to each of the scheduled ontreatment and posttreatment assessment time points;
5. Time to Run/Walk Test (TTRW): Change from Baseline to each of the scheduled on-treatment and post-treatment assessment time points; and
6. Quantitative Muscle Testing (QMT): Change from Baseline to each of the scheduled on-treatment and post-treatment assessment time points.

Exploratory Efficacy Endpoint:
To investigate the effects of vamorolone administered orally at daily doses up to 6.0 mg/kg over a 24-month Treatment Period on Quality of Life measures (PODCI)

Pharmacodynamic Endpoints:
Concentrations of serum and/or salivary PD biomarkers of adrenal suppression (morning salivary cortisol), insulin resistance (fasting insulin and glucose), and bone turnover (osteocalcin, serum carboxyterminal telopeptide of type I collagen [CTX1]).

Exploratory Endpoints:
Levels of an extended panel of PD efficacy and safety biomarkers using somaSCAN aptamer arrays, steroid hormone profiling, and other biomarker methods.

Endpoints for Subject Reported Outcomes:
Safety endpoints based on subject reports of AEs are listed in the protocol (section 2.2.1.2). Additionally, subjects' parents/legal guardians will be asked to complete the Pediatric Outcomes Data Collection Instrument. No other subject-reported outcomes are planned.

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

Secondary ID(s)

VBP15-LTE

2017-003568-10-SE

NCT03038399

Source(s) of Monetary Support

ReveraGen BioPharma Inc.

Ethics review

Status: Approved
Approval date: 05/01/2018
Contact: