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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02760277
Recruitment Status : Completed
First Posted : May 3, 2016
Results First Posted : July 23, 2019
Last Update Posted : July 23, 2019
Sponsor:
Collaborators:
University of Pittsburgh
National Institute of Neurological Disorders and Stroke (NINDS)
Cooperative International Neuromuscular Research Group
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Information provided by (Responsible Party):
ReveraGen BioPharma, Inc.

Brief Summary:
The main purposes of this study are to see if it is safe to use a new medication called vamorolone for more than two weeks in children with Duchenne muscular dystrophy (DMD), to see if vamorolone works for the treatment for DMD, and to see how any potential side effects compare to those seen in boys using steroids.

Condition or disease Intervention/treatment Phase
Duchenne Muscular Dystrophy Drug: Vamorolone 0.25 mg/day/day Drug: Vamorolone 0.75 mg/day/day Drug: Vamorolone 2.0 mg/day/day Drug: Vamorolone 6.0 mg/day/day Phase 2

Detailed Description:
This study will evaluate if it is safe to use a new medication called vamorolone for more than two weeks in children with DMD, if boys with DMD who take the study medication have improved muscle function compared to boys with DMD in other studies who did not take any type of steroid, and to see if boys with DMD who take the study medication gain less weight compared to boys with DMD in a prior study who took another type of steroid called prednisone. Enrolled participants will take the study medication for 24 weeks.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 48 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Open-label, Multicenter Extension Study to Assess the Long-term Safety and Efficacy of Vamorolone in Boys With Duchenne Muscular Dystrophy (DMD)
Actual Study Start Date : July 28, 2016
Actual Primary Completion Date : April 26, 2018
Actual Study Completion Date : April 26, 2018


Arm Intervention/treatment
Experimental: Dose Level Group 1
Participants enrolled in Dose Level Group 1 will receive vamorolone 0.25 mg/kg/day.
Drug: Vamorolone 0.25 mg/day/day
Oral administration of 0.25 mg/kg/day daily for 24 weeks.
Other Name: VBP15

Experimental: Dose Level Group 2
Participants enrolled in Dose Level Group 2 will receive vamorolone 0.75 mg/kg/day.
Drug: Vamorolone 0.75 mg/day/day
Oral administration of 0.75 mg/kg/day daily for 24 weeks.
Other Name: VBP15

Experimental: Dose Level Group 3
Participants enrolled in Dose Level Group 3 will receive vamorolone 2.0 mg/kg/day.
Drug: Vamorolone 2.0 mg/day/day
Oral administration of 2.0 mg/kg/day daily for 24 weeks.
Other Name: VBP15

Experimental: Dose Level Group 4
Participants enrolled in Dose Level Group 4 will receive vamorolone 6.0 mg/kg/day.
Drug: Vamorolone 6.0 mg/day/day
Oral administration of 6.0 mg/kg/day daily for 24 weeks.
Other Name: VBP15




Primary Outcome Measures :
  1. Number of Participants With Adverse Events as Assessed by CTCAE Version 4.03 [ Time Frame: 24 weeks ]
    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; To evaluate the long-term safety and tolerability of vamorolone, administered orally at daily doses up to 6.0 mg/kg/day over a 24- week Treatment Period, in boys ages 4-7 years with DMD.

  2. Total Number of Adverse Events as Assessed by CTCAE Version 4.03 [ Time Frame: 24 weeks ]
    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; To evaluate the long-term safety and tolerability of vamorolone, administered orally at daily doses up to 6.0 mg/kg/day over a 24- week Treatment Period, in boys ages 4-7 years with DMD.

  3. Muscle Function Measured by Time to Stand Test (TTSTAND)- Velocity [ Time Frame: 002 Baseline, 003 Baseline, 003 Week 12, Week 24 (Note: 002 Baseline is from VBP15-002 4 week study (NCT02760264), previous to VBP15-003) ]
    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

  4. BMI Z-score [ Time Frame: 002 Baseline, 003 Week 12, Week 24 ]

    Summary of BMI Z-score of Safety Population.

    Please note 0 is the mean. A negative result indicates a response that is many standard deviations below the mean, and a positive result indicates a response that is many standard deviations above the mean. In this case, the closer the group mean BMI Z-score is to 0 is more favorable.



Secondary Outcome Measures :
  1. Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c [ Time Frame: 002 Baseline, 003 Week 8, 003 Week 16, 003 Week 24, 003 Week 26-29 ]
    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). SomaScan aptamer panels testing 1,200 serum proteins were used to discover a candidate set of prednisone-responsive biomarkers, with a subset of these validating in a longitudinal sample set (individual DMD patients pre/post steroid treatment). These PD biomarkers were assigned to a safety panel or efficacy panel based on comparison to normal controls and information concerning the function of each protein.

  2. Serum Pharmacodynamics Biomarkers Measured by Levels of ACTH [ Time Frame: 002 Baseline, 003 Baseline, 003 Week 8, 003 Week 16, 003 Week 24, 003 Week 26-29 (Note: 002 Baseline is from VBP15-002 4 week study (NCT02760264), previous to VBP15-003) ]
    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). SomaScan aptamer panels testing 1,200 serum proteins were used to discover a candidate set of prednisone-responsive biomarkers, with a subset of these validating in a longitudinal sample set (individual DMD patients pre/post steroid treatment). These PD biomarkers were assigned to a safety panel or efficacy panel based on comparison to normal controls and information concerning the function of each protein.

  3. Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Glucose [ Time Frame: 002 Baseline, 003 Week 12, 003 Week 24 ]
    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). SomaScan aptamer panels testing 1,200 serum proteins were used to discover a candidate set of prednisone-responsive biomarkers, with a subset of these validating in a longitudinal sample set (individual DMD patients pre/post steroid treatment). These PD biomarkers were assigned to a safety panel or efficacy panel based on comparison to normal controls and information concerning the function of each protein.

  4. Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Insulin [ Time Frame: 002 Baseline, 003 Week 12, 003 Week 24 ]
    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). SomaScan aptamer panels testing 1,200 serum proteins were used to discover a candidate set of prednisone-responsive biomarkers, with a subset of these validating in a longitudinal sample set (individual DMD patients pre/post steroid treatment). These PD biomarkers were assigned to a safety panel or efficacy panel based on comparison to normal controls and information concerning the function of each protein.

  5. Serum Pharmacodynamics Biomarkers Measured by Levels of Osteocalcin [ Time Frame: 002 Baseline, 003 Baseline, 003 Week 8, 003 Week 16, 003 Week 24, 003 Week 26-29 (Note: 002 Baseline is from VBP15-002 4 week study (NCT02760264), previous to VBP15-003) ]
    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). SomaScan aptamer panels testing 1,200 serum proteins were used to discover a candidate set of prednisone-responsive biomarkers, with a subset of these validating in a longitudinal sample set (individual DMD patients pre/post steroid treatment). These PD biomarkers were assigned to a safety panel or efficacy panel based on comparison to normal controls and information concerning the function of each protein.

  6. Serum Pharmacodynamics Biomarkers Measured by Levels of P1NP [ Time Frame: 002 Baseline, 003 Baseline, 003 Week 8, 003 Week 16, 003 Week 24, 003 Week 26-29 (Note: 002 Baseline is from VBP15-002 4 week study (NCT02760264), previous to VBP15-003) ]
    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). SomaScan aptamer panels testing 1,200 serum proteins were used to discover a candidate set of prednisone-responsive biomarkers, with a subset of these validating in a longitudinal sample set (individual DMD patients pre/post steroid treatment). These PD biomarkers were assigned to a safety panel or efficacy panel based on comparison to normal controls and information concerning the function of each protein.

  7. Serum Pharmacodynamics Biomarkers Measured by Levels of CTX [ Time Frame: 002 Baseline, 003 Baseline, 003 Week 8, 003 Week 16, Week 24, 003 Week 26-29 (Note: 002 Baseline is from VBP15-002 4 week study (NCT02760264), previous to VBP15-003) ]
    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). SomaScan aptamer panels testing 1,200 serum proteins were used to discover a candidate set of prednisone-responsive biomarkers, with a subset of these validating in a longitudinal sample set (individual DMD patients pre/post steroid treatment). These PD biomarkers were assigned to a safety panel or efficacy panel based on comparison to normal controls and information concerning the function of each protein.

  8. Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Climb Test (TTCLIMB)- Velocity [ Time Frame: 002 Baseline, 003 Baseline, 003 Week 12, 003 Week 24 (Note: 002 Baseline is from VBP15-002 4 week study (NCT02760264), previous to VBP15-003) ]
    To investigate the effects of vamorolone, administered orally at daily doses up to 6.0 mg/kg over a 24-week Treatment Period, on muscle strength, mobility and functional exercise capacity vs. historical controls as measured by Time to Climb Test (TTCLIMB) in boys ages 4-7 years with DMD.

  9. Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Run/Walk 10 Meters Test (TTRW)- Velocity [ Time Frame: 002 Baseline, 003 Baseline, 003 Week 12, 003 Week 24 (Note: 002 Baseline is from VBP15-002 4 week study (NCT02760264), previous to VBP15-003) ]
    To investigate the effects of vamorolone, administered orally at daily doses up to 6.0 mg/kg over a 24-week Treatment Period, on muscle strength, mobility and functional exercise capacity vs. historical controls as measured by Time to Run/Walk Test (TTRW) in boys ages 4-7 years with DMD.

  10. Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by North Star Ambulatory Assessment (NSAA) [ Time Frame: 002 Baseline, 003 Baseline, 003 Week 12, 003 Week 24 (Note: 002 Baseline is from VBP15-002 4 week study (NCT02760264), previous to VBP15-003) ]
    To investigate the effects of vamorolone, administered orally at daily doses up to 6.0 mg/kg over a 24-week Treatment Period, on muscle strength, mobility and functional exercise capacity vs. historical controls as measured by North Star Ambulatory Assessment (NSAA) in boys ages 4-7 years with DMD. ***Total NSAA score is being reported. The score can range from 0 to 32. Higher scores (approaching 32) indicate a better outcome assessing functional mobility.

  11. Muscle Strength, Mobility, and Functional Exercise Capacity vs. Historical Controls as Measured by 6-minute Walk Test (6MWT) Meters [ Time Frame: 002 Baseline, 003 Baseline, 003 Week 12, 003 Week 24 (Note: 002 Baseline is from VBP15-002 4 week study (NCT02760264), previous to VBP15-003) ]
    To investigate the effects of vamorolone, administered orally at daily doses up to 6.0 mg/kg over a 24-week Treatment Period, on muscle strength, mobility and functional exercise capacity vs. historical controls as measured by 6-minute Walk Test (6MWT) in boys ages 4-7 years with DMD.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   4 Years to 7 Years   (Child)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Participant's parent or legal guardian has provided written informed consent/HIPAA authorization prior to any extension study-specific procedures;
  2. Participant has previously completed study VBP15-002 up to and including the Week 4 Follow-up assessments within 8 weeks prior to enrollment; and
  3. Participant and parent/guardian are willing and able to comply with scheduled visits, study drug administration plan, and study procedures.

Exclusion Criteria:

  1. Participant 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. Participant has current or history of major renal or hepatic impairment, diabetes mellitus or immunosuppression;
  3. Participant has current or history of chronic systemic fungal or viral infections;
  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. Subject 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; or
  11. Participant 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: Participants may be re-evaluated if ineligible due to a transient condition which would prevent the subject from participating


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02760277


Locations
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United States, California
University of California Davis
Davis, California, United States, 95616
United States, Florida
University of Florida
Gainesville, Florida, United States, 32611
Nemours Children's Hospital
Orlando, Florida, United States, 32827
United States, Illinois
Ann & Robert H. Lurie Children's Hospital
Chicago, Illinois, United States, 60611
United States, North Carolina
Duke University
Durham, North Carolina, United States, 27710
United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75207
Australia
Royal Children's Hospital
Melbourne, Australia
Sydney Children's Hospital
Westmead, Australia
Canada, Alberta
Alberta Children's Hospital
Calgary, Alberta, Canada, T3B 6A8
Israel
Schneider Children's Medical Center
Petah Tikwah, Israel, 49202
Sweden
Queen Silvia Children's Hospital
Gothenburg, Sweden, 41685
United Kingdom
Newcastle upon Tyne Hospitals NHS Foundation Trust
Newcastle upon Tyne, United Kingdom, NE7 7DN
Sponsors and Collaborators
ReveraGen BioPharma, Inc.
University of Pittsburgh
National Institute of Neurological Disorders and Stroke (NINDS)
Cooperative International Neuromuscular Research Group
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Investigators
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Study Chair: Paula R Clemens, MD University of Pittsburgh
  Study Documents (Full-Text)

Documents provided by ReveraGen BioPharma, Inc.:
Study Protocol  [PDF] February 22, 2017
Statistical Analysis Plan  [PDF] July 27, 2018


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Responsible Party: ReveraGen BioPharma, Inc.
ClinicalTrials.gov Identifier: NCT02760277     History of Changes
Other Study ID Numbers: VBP15-003
1R44NS095423-01 ( U.S. NIH Grant/Contract )
1U34AR068616-01 ( U.S. NIH Grant/Contract )
First Posted: May 3, 2016    Key Record Dates
Results First Posted: July 23, 2019
Last Update Posted: July 23, 2019
Last Verified: July 2019
Keywords provided by ReveraGen BioPharma, Inc.:
Duchenne muscular dystrophy
vamorolone
Additional relevant MeSH terms:
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Muscular Dystrophies
Muscular Dystrophy, Duchenne
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked