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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02760264




Registration number
NCT02760264
Ethics application status
Date submitted
28/04/2016
Date registered
3/05/2016
Date last updated
2/01/2019

Titles & IDs
Public title
A Study to Assess Vamorolone in Boys With Duchenne Muscular Dystrophy (DMD)
Scientific title
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)
Secondary ID [1] 0 0
1R44NS095423-01
Secondary ID [2] 0 0
VBP15-002
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/kg/day
Treatment: Drugs - Vamorolone 0.75 mg/kg/day
Treatment: Drugs - Vamorolone 2.0 mg/kg/day
Treatment: Drugs - Vamorolone 6.0 mg/kg/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/kg/day
Oral administration of 0.25 mg/kg/day daily for 14 days.

Treatment: Drugs: Vamorolone 0.75 mg/kg/day
Oral administration of 0.75 mg/kg/day daily for 14 days.

Treatment: Drugs: Vamorolone 2.0 mg/kg/day
Oral administration of 2.0 mg/kg/day daily for 14 days.

Treatment: Drugs: Vamorolone 6.0 mg/kg/day
Oral administration of 6 mg/kg/day daily for 14 days.

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

Outcomes
Primary outcome [1] 0 0
Overall Summary 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.
Note: Total Number of Treatment Emergent Adverse Events: The total incidences of TEAEs experienced in study; Any Treatment Emergent Adverse Event: TEAEs reported at least once per dose group
Timepoint [1] 0 0
Adverse events will be recorded from the date of informed consent and through the time of the subject's last study visit. Serious adverse events will be recorded from the date of informed consent and for up to 30 days after final drug administration.
Secondary outcome [1] 0 0
Serum Pharmacodynamic Biomarkers (Insulin Resistance)- Fasting Glucose - Pharmacodynamic biomarkers were measured to investigate the effects of single and multiple oral doses of vamorolone on serum PD biomarkers in ambulant boys ages 4-< 7 years with DMD.
Timepoint [1] 0 0
Baseline, Week 2
Secondary outcome [2] 0 0
Serum Pharmacodynamic Biomarkers (Insulin Resistance) -Fasting Glucose - Pharmacodynamic biomarkers were measured to investigate the effects of single and multiple oral doses of vamorolone on serum PD biomarkers in ambulant boys ages 4-< 7 years with DMD.
Timepoint [2] 0 0
Baseline, Week 2
Secondary outcome [3] 0 0
Serum Pharmacodynamic Biomarkers (Insulin Resistance)- Insulin - Pharmacodynamic biomarkers were measured to investigate the effects of single and multiple oral doses of vamorolone on serum PD biomarkers in ambulant boys ages 4-< 7 years with DMD.
Timepoint [3] 0 0
Baseline , Week 2
Secondary outcome [4] 0 0
Serum Pharmacodynamic Biomarkers (Insulin Resistance)- Insulin - Pharmacodynamic biomarkers were measured to investigate the effects of single and multiple oral doses of vamorolone on serum PD biomarkers in ambulant boys ages 4-< 7 years with DMD.
Timepoint [4] 0 0
Baseline, Week 2
Secondary outcome [5] 0 0
Serum Pharmacodynamic Biomarkers (Adrenal Axis Suppression)- First in Morning Cortisol - Pharmacodynamic biomarkers were measured to investigate the effects of single and multiple oral doses of vamorolone on serum PD biomarkers in ambulant boys ages 4-< 7 years with DMD.
Timepoint [5] 0 0
Week 2 (pre-dose)
Secondary outcome [6] 0 0
Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin - Pharmacodynamic biomarkers were measured to investigate the effects of single and multiple oral doses of vamorolone on serum PD biomarkers in ambulant boys ages 4-< 7 years with DMD.
Timepoint [6] 0 0
Baseline, Day 1, Week 2, Week 4
Secondary outcome [7] 0 0
Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide - Pharmacodynamic biomarkers were measured to investigate the effects of single and multiple oral doses of vamorolone on serum PD biomarkers in ambulant boys ages 4-< 7 years with DMD.
Timepoint [7] 0 0
Baseline Day 1 Week 2 Week 4
Secondary outcome [8] 0 0
Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide - Pharmacodynamic biomarkers were measured to investigate the effects of single and multiple oral doses of vamorolone on serum PD biomarkers in ambulant boys ages 4-< 7 years with DMD.
Timepoint [8] 0 0
Baseline, Day 1, Week 2, Week 4
Secondary outcome [9] 0 0
Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides - Pharmacodynamic biomarkers were measured to investigate the effects of single and multiple oral doses of vamorolone on serum PD biomarkers in ambulant boys ages 4-< 7 years with DMD.
Timepoint [9] 0 0
Baseline, Day 1, Week 4
Secondary outcome [10] 0 0
Pharmacokinetic (PK) Assessments (Tmax) - Plasma concentrations of vamorolone were measured using a specific and validated liquid chromatography tandem mass spectrometry (LC-MS) assay. tmax= time when plasma concentration is at maximum.
Timepoint [10] 0 0
Day 1, Week 2
Secondary outcome [11] 0 0
Pharmacokinetic (PK) Assessments (AUC Inf) - Plasma concentrations of vamorolone were measured using a specific and validated liquid chromatography tandem mass spectrometry (LC-MS) assay. AUC inf= Area under the concentration vs. time curve to time infinity.
Timepoint [11] 0 0
Day 1, Week 2
Secondary outcome [12] 0 0
Pharmacokinetic (PK) Assessments CL (ml/hr/kg) - Plasma concentrations of vamorolone were measured using a specific and validated liquid chromatography tandem mass spectrometry (LC-MS) assay
Timepoint [12] 0 0
Day 1, Week 2
Secondary outcome [13] 0 0
Pharmacokinetic (PK) Assessments t(1/2) - Plasma concentrations of vamorolone were measured using a specific and validated liquid chromatography tandem mass spectrometry (LC-MS) assay. t1/2= elimination half life.
Timepoint [13] 0 0
Day 1, Week 2
Secondary outcome [14] 0 0
Pharmacokinetic (PK) Assessments (Cmax) - Plasma concentrations of vamorolone were measured using a specific and validated liquid chromatography tandem mass spectrometry (LC-MS) assay
Timepoint [14] 0 0
Day 1, Week 2
Secondary outcome [15] 0 0
Metabolites in Safety Testing (MIST) Assessment - A portion of each blood sample of the Week 2 (Day 14) pharmacokinetic assessment time points for the subjects receiving vamorolone 2 mg/kg/day was used for analysis of vamorolone metabolites.
Timepoint [15] 0 0
Week 2 (Day 14)

Eligibility
Key inclusion criteria
1. Subject'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. Subject has a confirmed (by Central Genetic Counselor) diagnosis of DMD as defined as:

1. Dystrophin immunofluorescence and/or immunoblot showing complete dystrophin
deficiency, and clinical picture consistent with typical DMD, OR

2. 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

3. 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;

3. Subject is = 4 years and < 7 years of age at time of enrollment in the study;

4. Subject is able to complete the Time to Stand Test (TTSTAND) without assistance, as
assessed at the Screening 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. 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 testing
laboratory at the Screening Visit; and

7. Subject 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
6 Years
Gender
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 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;

11. Subject 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. Subject has previously been enrolled in the study.

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 Tikvah
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 Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Government body
Name [3] 0 0
National Institute of Neurological Disorders and Stroke (NINDS)
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
Cooperative International Neuromuscular Research Group
Address [4] 0 0
Country [4] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to determine whether a new medication called vamorolone is safe
and well-tolerated by boys with Duchenne muscular dystrophy (DMD) ages = 4 and < 7 years old.
Trial website
https://clinicaltrials.gov/show/NCT02760264
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