Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A 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: NCT02760264
Recruitment Status : Completed
First Posted : May 3, 2016
Results First Posted : January 1, 2019
Last Update Posted : January 1, 2019
Sponsor:
Collaborators:
University of Pittsburgh
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
National Institute of Neurological Disorders and Stroke (NINDS)
Cooperative International Neuromuscular Research Group
Information provided by (Responsible Party):
ReveraGen BioPharma, Inc.

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.

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

Detailed Description:
This study will evaluate the safety and tolerability of a new steroid-like medication called vamorolone in boys with DMD ages ≥ 4 years and < 7 years. Enrolled participants will take the study medication for 14 days followed by a 14 day follow-up period. The potential effectiveness of vamorolone in treating DMD will also be explored.

Layout table for study information
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 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)
Study Start Date : June 2016
Actual Primary Completion Date : May 1, 2018
Actual Study Completion Date : May 1, 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/kg/day
Oral administration of 0.25 mg/kg/day daily for 14 days.
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/kg/day
Oral administration of 0.75 mg/kg/day daily for 14 days.
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/kg/day
Oral administration of 2.0 mg/kg/day daily for 14 days.
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/kg/day
Oral administration of 6 mg/kg/day daily for 14 days.
Other Name: VBP15




Primary Outcome Measures :
  1. Overall Summary of Adverse Events as Assessed by CTCAE Version 4.03 [ Time Frame: 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. ]

    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



Secondary Outcome Measures :
  1. Serum Pharmacodynamic Biomarkers (Insulin Resistance)- Fasting Glucose [ Time Frame: Baseline, Week 2 ]
    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.

  2. Serum Pharmacodynamic Biomarkers (Insulin Resistance) -Fasting Glucose [ Time Frame: Baseline, Week 2 ]
    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.

  3. Serum Pharmacodynamic Biomarkers (Insulin Resistance)- Insulin [ Time Frame: Baseline , Week 2 ]
    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.

  4. Serum Pharmacodynamic Biomarkers (Insulin Resistance)- Insulin [ Time Frame: Baseline, Week 2 ]
    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.

  5. Serum Pharmacodynamic Biomarkers (Adrenal Axis Suppression)- First in Morning Cortisol [ Time Frame: Week 2 (pre-dose) ]
    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.

  6. Serum Pharmacodynamics Biomarkers (Bone Turnover) -Osteocalcin [ Time Frame: Baseline, Day 1, Week 2, Week 4 ]
    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.

  7. Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide [ Time Frame: Baseline Day 1 Week 2 Week 4 ]
    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.

  8. Serum Pharmacodynamic Biomarkers (Bone Turnover)- Procollagen 1 N-Terminal Propeptide [ Time Frame: Baseline, Day 1, Week 2, Week 4 ]
    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.

  9. Serum Pharmacodynamic Biomarkers (Bone Turnover)-Type I Collagen C-Telopeptides [ Time Frame: Baseline, Day 1, Week 4 ]
    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.

  10. Pharmacokinetic (PK) Assessments (Tmax) [ Time Frame: Day 1, Week 2 ]
    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.

  11. Pharmacokinetic (PK) Assessments (AUC Inf) [ Time Frame: Day 1, Week 2 ]
    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.

  12. Pharmacokinetic (PK) Assessments CL (ml/hr/kg) [ Time Frame: Day 1, Week 2 ]
    Plasma concentrations of vamorolone were measured using a specific and validated liquid chromatography tandem mass spectrometry (LC-MS) assay

  13. Pharmacokinetic (PK) Assessments t(1/2) [ Time Frame: Day 1, Week 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.

  14. Pharmacokinetic (PK) Assessments (Cmax) [ Time Frame: Day 1, Week 2 ]
    Plasma concentrations of vamorolone were measured using a specific and validated liquid chromatography tandem mass spectrometry (LC-MS) assay

  15. Metabolites in Safety Testing (MIST) Assessment [ Time Frame: Week 2 (Day 14) ]
    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.



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.


Layout table for eligibility information
Ages Eligible for Study:   4 Years to 6 Years   (Child)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

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.

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.

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): NCT02760264


Locations
Layout table for location information
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 Tikvah, 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 Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
National Institute of Neurological Disorders and Stroke (NINDS)
Cooperative International Neuromuscular Research Group
Investigators
Layout table for investigator information
Study Chair: Paula R Clemens, MD University of Pittsburgh
  Study Documents (Full-Text)

Documents provided by ReveraGen BioPharma, Inc.:
Study Protocol  [PDF] January 20, 2017
Statistical Analysis Plan  [PDF] January 31, 2018


Additional Information:
Layout table for additonal information
Responsible Party: ReveraGen BioPharma, Inc.
ClinicalTrials.gov Identifier: NCT02760264     History of Changes
Other Study ID Numbers: VBP15-002
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: January 1, 2019
Last Update Posted: January 1, 2019
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by ReveraGen BioPharma, Inc.:
Duchenne Muscular Dystrophy
vamorolone
Additional relevant MeSH terms:
Layout table for MeSH terms
Muscular Dystrophies
Muscular Dystrophy, Duchenne
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked