- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02760277
An Extension Study to Assess Vamorolone in Boys With Duchenne Muscular Dystrophy (DMD)
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)
Study Overview
Status
Conditions
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Melbourne, Australia
- Royal Children's Hospital
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Westmead, Australia
- Sydney Children's Hospital
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Alberta
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Calgary, Alberta, Canada, T3B 6A8
- Alberta Children's Hospital
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Petah Tikwah, Israel, 49202
- Schneider Children's Medical Center
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Gothenburg, Sweden, 41685
- Queen Silvia Children's Hospital
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Newcastle upon Tyne, United Kingdom, NE7 7DN
- Newcastle upon Tyne Hospitals NHS Foundation Trust
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California
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Davis, California, United States, 95616
- University of California Davis
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Florida
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Gainesville, Florida, United States, 32611
- University of Florida
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Orlando, Florida, United States, 32827
- Nemours Children's Hospital
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Illinois
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Chicago, Illinois, United States, 60611
- Ann & Robert H. Lurie Children's Hospital
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North Carolina
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Durham, North Carolina, United States, 27710
- Duke University
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Texas
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Dallas, Texas, United States, 75207
- University of Texas Southwestern Medical Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Participant's parent or legal guardian has provided written informed consent/HIPAA authorization prior to any extension study-specific procedures;
- Participant has previously completed study VBP15-002 up to and including the Week 4 Follow-up assessments within 8 weeks prior to enrollment; and
- Participant and parent/guardian are willing and able to comply with scheduled visits, study drug administration plan, and study procedures.
Exclusion Criteria:
- 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;
- Participant has current or history of major renal or hepatic impairment, diabetes mellitus or immunosuppression;
- Participant has current or history of chronic systemic fungal or viral infections;
- 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;
- Participant has evidence of symptomatic cardiomyopathy. [Note: Asymptomatic cardiac abnormality on investigation would not be exclusionary];
- 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];
- Subject has used idebenone within 4 weeks prior to the first dose of study medication;
- Participant has an allergy or hypersensitivity to the study medication or to any of its constituents;
- Participant has severe behavioral or cognitive problems that preclude participation in the study, in the opinion of the Investigator;
- 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
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Dose Level Group 1
Participants enrolled in Dose Level Group 1 will receive vamorolone 0.25 mg/kg/day.
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Oral administration of 0.25 mg/kg/day daily for 24 weeks.
Other Names:
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Experimental: Dose Level Group 2
Participants enrolled in Dose Level Group 2 will receive vamorolone 0.75 mg/kg/day.
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Oral administration of 0.75 mg/kg/day daily for 24 weeks.
Other Names:
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Experimental: Dose Level Group 3
Participants enrolled in Dose Level Group 3 will receive vamorolone 2.0 mg/kg/day.
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Oral administration of 2.0 mg/kg/day daily for 24 weeks.
Other Names:
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Experimental: Dose Level Group 4
Participants enrolled in Dose Level Group 4 will receive vamorolone 6.0 mg/kg/day.
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Oral administration of 6.0 mg/kg/day daily for 24 weeks.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Number of Participants With Adverse Events as Assessed by CTCAE Version 4.03
Time Frame: 24 weeks
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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.
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24 weeks
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Total Number of Adverse Events as Assessed by CTCAE Version 4.03
Time Frame: 24 weeks
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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.
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24 weeks
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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)
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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
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002 Baseline, 003 Baseline, 003 Week 12, Week 24 (Note: 002 Baseline is from VBP15-002 4 week study (NCT02760264), previous to VBP15-003)
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BMI Z-score
Time Frame: 002 Baseline, 003 Week 12, Week 24
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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. |
002 Baseline, 003 Week 12, Week 24
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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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
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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.
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002 Baseline, 003 Week 8, 003 Week 16, 003 Week 24, 003 Week 26-29
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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)
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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.
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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)
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Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Glucose
Time Frame: 002 Baseline, 003 Week 12, 003 Week 24
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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.
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002 Baseline, 003 Week 12, 003 Week 24
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Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Insulin
Time Frame: 002 Baseline, 003 Week 12, 003 Week 24
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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.
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002 Baseline, 003 Week 12, 003 Week 24
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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)
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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.
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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)
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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)
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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.
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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)
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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)
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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.
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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)
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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)
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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.
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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)
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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)
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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.
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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)
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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)
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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.
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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)
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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)
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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.
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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)
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Chair: Paula R Clemens, MD, University of Pittsburgh
Publications and helpful links
General Publications
- Smith EC, Conklin LS, Hoffman EP, Clemens PR, Mah JK, Finkel RS, Guglieri M, Tulinius M, Nevo Y, Ryan MM, Webster R, Castro D, Kuntz NL, Kerchner L, Morgenroth LP, Arrieta A, Shimony M, Jaros M, Shale P, Gordish-Dressman H, Hagerty L, Dang UJ, Damsker JM, Schwartz BD, Mengle-Gaw LJ, McDonald CM; CINRG VBP15 and DNHS Investigators. Efficacy and safety of vamorolone in Duchenne muscular dystrophy: An 18-month interim analysis of a non-randomized open-label extension study. PLoS Med. 2020 Sep 21;17(9):e1003222. doi: 10.1371/journal.pmed.1003222. eCollection 2020 Sep.
- Li X, Conklin LS, van den Anker J, Hoffman EP, Clemens PR, Jusko WJ. Exposure-Response Analysis of Vamorolone (VBP15) in Boys With Duchenne Muscular Dystrophy. J Clin Pharmacol. 2020 Oct;60(10):1385-1396. doi: 10.1002/jcph.1632. Epub 2020 May 20.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- VBP15-003
- 1R44NS095423-01 (U.S. NIH Grant/Contract)
- 1U34AR068616-01 (U.S. NIH Grant/Contract)
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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