A Study to Assess Vamorolone in Boys With Duchenne Muscular Dystrophy (DMD)

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2016-004462-26-GB
• Date of registration: 23/12/2016
• Prospective Registration: Yes
• Primary sponsor: ReveraGen BioPharma, Inc.
• Public title: A Study to Assess Vamorolone in Boys With Duchenne Muscular Dystrophy (DMD)
• Scientific title: VBP15-002 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)
• Date of first enrolment: 16/02/2017
• Target sample size: 48
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-004462-26
• 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, 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. Participant’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. Participant has a confirmed (by Central Genetic Counselor) diagnosis of DMD as defined as:
a) Dystrophin immunofluorescence and/or immunoblot showing complete dystrophin deficiency, and clinical picture
consistent with typical DMD, OR
b) 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
c) 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;
Participant is = 4 years and < 7 years of age at time of enrollment in the study;
4. Participant is able to complete the Time to Stand Test (TTSTAND) without assistance, as assessed at the Screening
or 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.Participant 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. Participant and caregiver 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. Participant has current or history of major renal or hepatic impairment, diabetes mellitus or immunosuppression;
2. Participant has current or history of chronic systemic fungal or viral infections;
3. Participant has had an acute illness within 4 weeks prior to the first dose of study medication;
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. Participant 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;
11.Participant 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.Participant has previously been enrolled in the study.
Note: Any parameter/test may be repeated at the Investigator's
discretion during Screening and/or Day 1 to determine sustainability
and 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 if ineligible
due to negative anti-varicella IgG antibody test result.



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

Health Condition(s) or Problem(s) studied

Duchenne muscular dystrophy (DMD)
MedDRA version: 19.0 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)

Secondary Objective: 1. To investigate the single-dose and multiple-dose pharmacokinetics (PK) of oral vamorolone at multiple dose levels in ambulant boys ages 4-< 7 years with DMD;
2. To investigate the effects of single and multiple oral doses of vamorolone on serum pharmacodynamic (PD) biomarkers in ambulant boys ages 4-< 7 years with DMD;
3. To evaluate metabolites of vamorolone in Metabolites in Safety Testing (MIST) assessments following administration of multiple ascending oral doses.

Primary end point(s): Safety Endpoints
1. Treatment-emergent adverse events (TEAEs) and serious adverse
events (SAEs), by system organ class (SOC): overall by treatment, by
treatment and relationship, by treatment and outcome, and by treatment
and intensity (Common Terminology Criteria for Adverse Events [CTCAE]
grade);
2. Vital sign [supine blood pressure (BP), heart rate, respiratory rate,
oral temperature] values: change from Pretreatment to each of the
scheduled on-treatment and post-treatment assessment time points;
3. Body weight: change from Pretreatment to each of the scheduled ontreatment
and post-treatment assessment time points;
4. Clinical laboratory values: change from Pretreatment to each of the
scheduled on-treatment and post-treatment assessment time points in:
- Hematology and biochemistry
- Lipid profile (triglycerides, total cholesterol, low density lipoprotein
[LDL], high density lipoprotein [HDL])
- Urinalysis (urine protein and glucose);
5. Concentrations of serum metabolites of vamorolone;
6. 12-lead electrocardiogram (ECG) results: change from Pretreatment to
Day 14 and Day 28; and
7. Physical examination findings of abnormality.

Main Objective: To evaluate the safety and tolerability of multiple ascending oral doses of vamorolone in ambulant boys ages 4-< 7 years with DMD

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

Secondary Outcome(s)

Secondary end point(s): Pharmacodynamic Endpoints
1. Concentration of acute and chronic serum PD biomarkers (change
from Pretreatment to on-treatment and post-treatment time points):
osteocalcin, serum aminoterminal propeptide of type I collagen (P1NP),
carboxy-terminal telopeptide (CTX), cortisol, ACTH, 17-
hydroxyprogesterone, testosterone, corticosterone, and 11-
deoxycortisol, insulin, and glucose and SomaScan and proteomics
profiling.
Exploratory Clinical Efficacy Endpoints
All exploratory clinical efficacy measures are assessed as change from
Pretreatment to each of the scheduled on-treatment and post-treatment
assessment time points:
1. Quantitative Muscle Testing (QMT): unilateral elbow and knee muscle
flexion and extension;
2. Time to Stand Test (TTSTAND) from a supine position;
3. Time to Climb 4 Steps Test (TTCLIMB);
4. Time to Run/Walk 10 meters Test (TTRW);
5. North Star Ambulatory Assessment (NSAA); and
6. Six-minute Walk Test (6MWT).
Acceptability of vamorolone by a 5-point hedonic scale. Assessed ontreatment
and post-treatment assessment time points
Pharmacokinetic Endpoints
Plasma PK parameters derived from serial blood samples collected 0.5
hour pre-dose and 1, 2, 4, 6, and 8 hours after the first and final doses of study drug on Day 1 and Day 14.

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

Secondary ID(s)

VBP15-002

NCT02760264

Source(s) of Monetary Support

ReveraGen BioPharma, Inc.

Ethics review

Status: Approved
Approval date:
Contact: