A Study to Assess the Efficacy and Safety of Vamorolone in Boys With Duchenne Muscular Dystrophy (DMD)

March 7, 2023 updated by: ReveraGen BioPharma, Inc.

A Phase IIb Randomized, Double-blind, Parallel Group, Placebo- and Active-controlled Study With Double-Blind Extension to Assess the Efficacy and Safety of Vamorolone in Ambulant Boys With Duchenne Muscular Dystrophy (DMD)

Brief Summary: This Phase IIb study is a randomized, double-blind, parallel group, placebo and active-controlled study to evaluate the efficacy, safety, PD, and population PK of vamorolone administered orally at daily doses of 2.0 mg/kg and 6.0 mg/kg versus prednisone 0.75 mg/kg/day and placebo over a Treatment Period of 24 weeks, and to evaluate persistence of effect over a Treatment Period of 48 weeks in ambulant boys ages 4 to <7 years with DMD.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This Phase IIb study is a randomized, double-blind, parallel group, placebo and active-controlled study to evaluate the efficacy, safety, PD, and population PK of vamorolone administered orally at daily doses of 2.0 mg/kg and 6.0 mg/kg versus prednisone 0.75 mg/kg/day and placebo over a Treatment Period of 24 weeks, and to evaluate persistence of effect over a Treatment Period of 48 weeks in ambulant boys ages 4 to <7 years with DMD.

The study is comprised of a 5-week Pretreatment Screening Period, a 1-day Pretreatment Baseline Period, a 24-week Treatment Period #1 (Weeks 1-24), a 4-week Transition Period (Weeks 25-28), a 20-week Treatment Period #2 (Weeks 28 + 1 day to 48), and a 4-week Dose-tapering Period (Weeks 49-52).

Subjects will be randomized to one of six treatment groups in a 2:2:1:1:1:1 ratio, where the two prednisone groups in Treatment Period #1 (Groups 3 and 4) will be combined and the two placebo groups in Treatment Period #1 (Groups 5 and 6) will be combined, effectively resulting in a 1:1:1:1 randomization (vamorolone 2.0 mg/kg/day : vamorolone 6.0 mg/kg/day : prednisone 0.75 mg/kg/day : placebo) for Treatment Period #1.

Subjects will be stratified based on age at study entry (<6 vs. ≥ 6 years). During the 4-week Transition Period between Treatment Period #1 and Treatment Period #2, all subjects will continue on the same oral suspension (vamorolone 2.0 mg/kg or 6.0 mg/kg, or matching placebo) they received during Treatment Period #1 and all subjects will have their tablet dose tapered to zero. Thus, subjects randomized to receive vamorolone during Treatment Period #1 (Groups 1 and 2) will continue to receive vamorolone at the same dose, while subjects randomized to receive prednisone will have their dose tapered to zero, and subjects randomized to placebo will continue to receive placebo.

The prednisone group will be used as an active control comparison for safety and efficacy endpoints as requested by the European Medicines Agency (EMA). The placebo group will be used as comparator for efficacy endpoints (superiority model) as requested by the EMA and Food and Drug Administration (FDA) protocol advisory board. Although glucocorticoids are part of the care recommendations for DMD, their adverse effect profile has limited their use. The age at which glucocorticoids should be started in DMD boys is uncertain, ranging from 4 to 7 years, based on a balance between benefits and side effects. In view of the age inclusion criteria and duration of the placebo-controlled study period (6 months), the use of a placebo group has been considered acceptable as in clinical practice it will not cause a real delay in prescription of an accepted treatment for this condition. Any exposure of placebo longer than 6 months was considered unethical.

At the end of the Treatment Period #2, subjects may be given access to vamorolone through an additional study or general access program, or given the option to transition to standard of care treatment for DMD (may include glucocorticoids). Subjects completing VBP15-004 and enrolling directly into an additional vamorolone study or general access program to receive vamorolone will not need to taper their vamorolone dose prior to enrollment. All other subjects will begin a 4-week double-blind Dose-tapering Period during which the dose of study medication will be progressively reduced and discontinued.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
121

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Melbourne, Australia
        • Royal Children's Hospital
      • Westmead, Australia
        • Sydney Children's Hospital
  • Belgium
      • Ghent, Belgium
        • Ghent University Hospital
      • Leuven, Belgium
        • University Hospitals Leuven
  • Canada
    • Alberta
      • Calgary, Alberta, Canada, AB T3B 6A8
        • Alberta'S Children Hospital
    • British Columbia
      • Vancouver, British Columbia, Canada, V6H 3N1
        • British Columbia Children's Hospital
    • Ontario
      • Ottawa, Ontario, Canada, K1H 8L1
        • Children's Hospital of Eastern Ontario
    • Quebec
      • Montréal, Quebec, Canada, H4A 3J1
        • Montreal Children's Hospital
  • Czechia
      • Brno, Czechia
        • University Hospital Brno
      • Prague, Czechia
        • Charles University
  • Greece
      • Athens, Greece
        • Agia Sofia Children's Hospital
  • Israel
      • Petah Tikvah, Israel, 49202
        • Schneider Children's Medical Center
  • Netherlands
      • Leiden, Netherlands
        • Leiden University Medical Center
      • Nijmegen, Netherlands
        • Radboud University
  • Spain
      • Barcelona, Spain
        • Sant Joan de Deu Hospital - Barcelona, Spain
      • Valencia, Spain
        • Hospital Universitario y Politécnico La Fe
  • Sweden
      • Gothenburg, Sweden, 41685
        • Queen Silvia Children's Hospital
  • United Kingdom
      • Birmingham, United Kingdom
        • Birmingham Heartlands Hospital
      • Glasgow, United Kingdom, G51 4TF
        • Royal Hospital For Children
      • Leeds, United Kingdom
        • Leeds Teaching Hospital Trust
      • Liverpool, United Kingdom, L12 2AP
        • Alder Hey Children's NHS Foundation Trust
      • London, United Kingdom
        • Great Ormond Street Hospital
      • Newcastle upon Tyne, United Kingdom, NE7 7DN
        • Newcastle upon Tyne Hospitals NHS Foundation Trust
  • United States
    • California
      • Davis, California, United States, 95616
        • University of California Davis
      • Los Angeles, California, United States, 90095
        • University of California Los Angeles
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Children's Hospital Colorado
    • Florida
      • Orlando, Florida, United States, 32827
        • Nemours Children's Hospital
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Ann & Robert H. Lurie Children's Hospital
    • Minnesota
      • Saint Paul, Minnesota, United States, 55101
        • Gillette Children's Speciality Health Care
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke Children's Hospital
    • Texas
      • Dallas, Texas, United States, 75207
        • University of Texas Southwestern Medical Center
    • Virginia
      • Richmond, Virginia, United States, 23219
        • Children's Hospital of Virginia of Virginia Commonwealth University
    • Washington
      • Seattle, Washington, United States, 98105
        • Seattle Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

4 years to 7 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  1. Subject's parent(s) or legal guardian(s) has (have) provided written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization, where applicable, prior to any study-related procedures; participants will be asked to give written or verbal assent according to local requirements

  2. Subject has a centrally confirmed (by TRiNDS central genetic counselor[s]) diagnosis of DMD as defined as:

    • Dystrophin immunofluorescence and/or immunoblot showing complete dystrophin deficiency, and clinical picture consistent with typical DMD, OR
    • 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
    • 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 clinical picture consistent with typical DMD;
  3. Subject is ≥ 4 years and <7 years of age at time of enrollment in the study;
  4. Subject weighs >13.0 kg and ≤ 39.9 kg at the Screening Visit;
  5. Subject is able to walk independently without assistive devices;
  6. Subject is able to complete the Time to Stand Test (TTSTAND) without assistance in <10 seconds, as assessed at the Screening Visit;
  7. 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. [Notes: Serum gamma glutamyl transferase (GGT), creatinine, and total bilirubin all must be ≤ upper limit of the normal range at the Screening Visit. An abnormal vitamin D level that is considered clinically significant will not exclude a subject from randomization];

  8. 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 local laboratory from blood collected during the Screening Period, OR
    • Documentation, provided at the Screening Visit, that the subject has had 2 doses of varicella vaccine, with or without serologic evidence of immunity; the second of the 2 immunizations must have been given at least 14 days prior to randomization.
  9. Subject is able to swallow tablets, as confirmed by successful test swallowing of placebo tablets during the Screening Period; and
  10. Subject and parent(s)/guardian(s) are willing and able to comply with scheduled visits, study drug administration plan, and study procedures.

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 a history of primary hyperaldosteronism;
  6. Subject has evidence of symptomatic cardiomyopathy [Note: Asymptomatic cardiac abnormality on investigation would not be exclusionary];
  7. 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 1 month 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, unless discontinued for intolerance. Inhaled and/or topical glucocorticoids are permitted if last use is at least 4 weeks prior to first dose of study medication or if administered at stable dose beginning at least 4 weeks prior to first dose of study medication and anticipated to be used at the stable dose regimen for the duration of the study];
  8. Subject has an allergy or hypersensitivity to the study medication or to any of its constituents;
  9. Subject has used idebenone within 4 weeks prior to the first dose of study medication;
  10. Subject has severe behavioral or cognitive problems that preclude participation in the study, in the opinion of the Investigator;
  11. 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;
  12. Subject is taking (or has taken within 4 weeks prior to the first dose of study medication) herbal remedies and supplements which can impact muscle strength and function (e.g., Co-enzyme Q10, creatine, etc);
  13. Subject is taking (or has taken within 3 months prior to the first dose of study medication) any medication indicated for DMD, including Exondys51 and Translarna;
  14. Subject has been administered a live attenuated vaccine within 14 days prior to the first dose of study medication;
  15. Subject is currently taking any other investigational drug or has taken any other investigational drug within 3 months prior to the first dose of study medication;
  16. Subject has a sibling who is currently enrolled in any vamorolone study or Expanded Access Program, or who intends to enroll in any vamorolone study or Expanded Access Program during the subject's participation in the VBP15-004 study; or
  17. Subject has previously been enrolled in the study. Note: Any parameter/test may be repeated at the Investigator's discretion during Screening to determine 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 injury, or if ineligible due to negative anti-varicella IgG antibody test result.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Treatment Group 1
Patients enrolled in Treatment Group 1 (experimental group) will receive vamorolone 2.0 mg/kg/day for the duration of the study.
Drug: Vamorolone
Oral administration of 2.0 mg/kg/day for the duration of the study.
Other Names:
  • VBP15
Drug: Vamorolone
Oral administration of 6.0 mg/kg/day for the duration of the study.
Other Names:
  • VBP15
Drug: Vamorolone
Oral administration of 2.0 mg/kg/day for 20 weeks.
Other Names:
  • VBP15
Drug: Vamorolone
Oral administration of 6.0 mg/kg/day for 20 weeks.
Other Names:
  • VBP15
Experimental: Treatment Group 2
Patients enrolled in Treatment Group 2 (experimental group) will receive vamorolone at 6.0 mg/kg/day for the duration of the study.
Drug: Vamorolone
Oral administration of 2.0 mg/kg/day for the duration of the study.
Other Names:
  • VBP15
Drug: Vamorolone
Oral administration of 6.0 mg/kg/day for the duration of the study.
Other Names:
  • VBP15
Drug: Vamorolone
Oral administration of 2.0 mg/kg/day for 20 weeks.
Other Names:
  • VBP15
Drug: Vamorolone
Oral administration of 6.0 mg/kg/day for 20 weeks.
Other Names:
  • VBP15
Active Comparator: Treatment Group 3
Patients enrolled in Treatment Group 3 (active comparator group) will receive prednisone 0.75 mg/kg/day for 24 weeks followed by 20 weeks of treatment with 2.0 mg/kg/day vamorolone.
Drug: Vamorolone
Oral administration of 2.0 mg/kg/day for the duration of the study.
Other Names:
  • VBP15
Drug: Vamorolone
Oral administration of 6.0 mg/kg/day for the duration of the study.
Other Names:
  • VBP15
Drug: Vamorolone
Oral administration of 2.0 mg/kg/day for 20 weeks.
Other Names:
  • VBP15
Drug: Vamorolone
Oral administration of 6.0 mg/kg/day for 20 weeks.
Other Names:
  • VBP15
Drug: Prednisone
Oral administration of 0.75 mg/kg/day for 24 weeks.
Active Comparator: Treatment Group 4
Patients enrolled in Treatment Group 4 (active comparator group) will receive prednisone 0.75 mg/kg/day for 24 weeks followed by 20 weeks treatment with 6.0 mg/kg/day vamorolone.
Drug: Vamorolone
Oral administration of 2.0 mg/kg/day for the duration of the study.
Other Names:
  • VBP15
Drug: Vamorolone
Oral administration of 6.0 mg/kg/day for the duration of the study.
Other Names:
  • VBP15
Drug: Vamorolone
Oral administration of 2.0 mg/kg/day for 20 weeks.
Other Names:
  • VBP15
Drug: Vamorolone
Oral administration of 6.0 mg/kg/day for 20 weeks.
Other Names:
  • VBP15
Drug: Prednisone
Oral administration of 0.75 mg/kg/day for 24 weeks.
Placebo Comparator: Treatment Group 5
Patients enrolled in Treatment Group 5 (placebo comparator group) will receive placebo daily for 24 weeks followed by 20 weeks treatment with 2.0 mg/kg/day vamorolone.
Drug: Vamorolone
Oral administration of 2.0 mg/kg/day for the duration of the study.
Other Names:
  • VBP15
Drug: Vamorolone
Oral administration of 6.0 mg/kg/day for the duration of the study.
Other Names:
  • VBP15
Drug: Vamorolone
Oral administration of 2.0 mg/kg/day for 20 weeks.
Other Names:
  • VBP15
Drug: Vamorolone
Oral administration of 6.0 mg/kg/day for 20 weeks.
Other Names:
  • VBP15
Other: Placebo
Oral administration of placebo daily for 24 weeks.
Placebo Comparator: Treatment Group 6
Patients enrolled in Treatment Group 6 (placebo comparator group) will receive placebo daily for 24 weeks followed by 20 weeks treatment with 6.0 mg/kg/day vamorolone.
Drug: Vamorolone
Oral administration of 2.0 mg/kg/day for the duration of the study.
Other Names:
  • VBP15
Drug: Vamorolone
Oral administration of 6.0 mg/kg/day for the duration of the study.
Other Names:
  • VBP15
Drug: Vamorolone
Oral administration of 2.0 mg/kg/day for 20 weeks.
Other Names:
  • VBP15
Drug: Vamorolone
Oral administration of 6.0 mg/kg/day for 20 weeks.
Other Names:
  • VBP15
Other: Placebo
Oral administration of placebo daily for 24 weeks.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Efficacy Measured by Time to Stand Test (TTSTAND) Velocity in Rises/Second Change From Baseline
Time Frame: 24 weeks
Vamorolone at 6.0mg/kg/day vs. placebo group in change from baseline to the Week 24 assessment
24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
ReveraGen BioPharma, Inc.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University of Pittsburgh
Newcastle University
European Union
Cooperative International Neuromuscular Research Group

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 29, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 23, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 19, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 9, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 13, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 20, 2018

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 9, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 7, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • VBP15-004

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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