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A Study to Assess Vamorolone in Becker Muscular Dystrophy (BMD)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05166109
Recruitment Status : Recruiting
First Posted : December 21, 2021
Last Update Posted : April 4, 2024
Sponsor:
Collaborator:
Santhera Pharmaceuticals
Information provided by (Responsible Party):
ReveraGen BioPharma, Inc.

Brief Summary:

This Phase II pilot study is a randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, PK, PD, and exploratory clinical efficacy of vamorolone 500mg (250mg for body weight <50 kg) daily administered orally compared to placebo over a treatment period of 24 weeks in males with BMD.

Funding Source - FDA OOPD


Condition or disease Intervention/treatment Phase
Becker Muscular Dystrophy Drug: Vamorolone Drug: Placebo Phase 2

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

Show Show detailed description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 39 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase II Pilot Trial of Vamorolone vs. Placebo for the Treatment of Becker Muscular Dystrophy
Actual Study Start Date : July 7, 2022
Estimated Primary Completion Date : January 31, 2025
Estimated Study Completion Date : January 31, 2025


Arm Intervention/treatment
Experimental: Vamorolone 500mg/day [250mg if <50kg body weight]
Subjects will be randomized to one of two treatment groups in a 1:2 ratio (placebo:vamorolone).
Drug: Vamorolone
Vamorolone 4.0% wt/wt oral suspension will be administered for the duration of the study.
Other Name: VBP15

Placebo Comparator: Placebo
Subjects will be randomized to one of two treatment groups in a 1:2 ratio (placebo:vamorolone).
Drug: Placebo
Placebo to Vamorolone 4.0% wt/wt oral suspension will be administered for the duration of the study.
Other Name: Placebo to vamorolone




Primary Outcome Measures :
  1. Safety as measured by Treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) by system organ class (SOC and PT) [ Time Frame: 24 weeks ]

    Clinical AEs and clinical laboratory AEs will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.03, dated June 14, 2010.

    Dose-limiting toxicities will be defined as follows:

    1. The presence of a CTCAE Grade ≥ 3 AE, considered to be probably or definitely related to study drug
    2. The presence of a CTCAE Grade ≥ 3 clinical laboratory AE considered to be probably or definitely related to study drug
    3. Deterioration of the muscle condition, unexpected for the natural course of BMD and without other clear cause

  2. Safety as measured by Sitting Blood Pressure [ Time Frame: Day 1, Week 4, Week 12, Week 24, Week 28 ]
    Change in Sitting Blood Pressure from baseline to each of the scheduled on-treatment and post-treatment assessment time points for each treatment group.

  3. Safety as measured by Heart Rate [ Time Frame: Day 1, Week 4, Week 12, Week 24, Week 28 ]
    Change in Heart Rate from baseline to each of the scheduled on-treatment and post-treatment assessment time points for each treatment group.

  4. Safety as measured by Respiratory Rate [ Time Frame: Day 1, Week 4, Week 12, Week 24, Week 28 ]
    Change in Respiratory Rate from baseline to each of the scheduled on-treatment and post-treatment assessment time points for each treatment group.

  5. Safety as measured by Body Temperature [ Time Frame: Day 1, Week 4, Week 12, Week 24, Week 28 ]
    Change in Body Temperature from baseline to each of the scheduled on-treatment and post-treatment assessment time points for each treatment group.

  6. Safety as measured by Body Weight [ Time Frame: Week 12, Week 24, Week 28 ]
    Change in Body Weight from baseline to each of the scheduled on-treatment and post-treatment assessment time points for each treatment group.

  7. Safety as measured by Height [ Time Frame: Week 12, Week 24, Week 28 ]
    Change in Height from screening to each of the scheduled on-treatment and post-treatment assessment time points for each treatment group.

  8. Safety: concentration of blood laboratory biomarkers as assessed by standardized clinical laboratory reference ranges [ Time Frame: Week 4, Week 12, Week 24 ]
    Blood biomarkers are White Blood cells (WBCs), Red Blood Cells, (RBCs), hemoglobin, Platelets, Sodium, Potassium, Chloride, Calcium, Blood Urea Nitrogen (BUN), Creatinine, Total Protein, Albumin, Total Bilirubin, Glucose, Alkaline Phosphatase (ALP), Gamma Glutamyl Transferase (GGT), Glutamate Dehydrogenase (GLDH), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Creatine kinase (CK), Bicarbonate, Triglycerides, Total cholesterol, Low Density Lipoprotein (LDL) and High density Lipoprotein (HDL). Change from baseline to each of the scheduled on treatment and post-treatment time points will be assessed.

  9. Safety: concentration of urine laboratory biomarkers as measured by dipstick and microscopic analysis [ Time Frame: Week 4, Week 12, Week 24 ]
    Urine biomarkers are protein, glucose, ketones, leukocyte esterase, White Blood Cells (WBCs), Red Blood Cells, (RBCs) and bacteria. Change from baseline to each of the scheduled on treatment and post-treatment time points will be assessed.

  10. Safety as measured by 12-lead ECG [ Time Frame: Week 12, Week 24 ]
    12-lead ECG as recorded after subject has rested quietly in a supine position for at least 5 minutes. ECG components are QRS duration, PR interval, QT interval and QTc interval. Change from baseline to each of the scheduled on-treatment and post-treatment assessment time points.

  11. Tolerability as measured by incidence of Premature Discontinuation [ Time Frame: 24 weeks ]
    Premature Discontinuation of study treatment due to adverse event.


Secondary Outcome Measures :
  1. Pharmacokinetics as measured by AUCinf [ Time Frame: Day 1 ]
    Blood will be collected from all subjects at the Day 1 Visit, at 1, 2 and 3 hours post-dose, for vamorolone PK analysis

  2. Safety as measured by serum concentration of osteocalcin [ Time Frame: Week 24 ]
    Change from baseline to Week 24 will be assessed for each treatment group.

  3. Safety as measured by serum concentration of hemoglobin A1c (HbA1c) [ Time Frame: Week 24 ]
    Change from baseline to Week 24 will be assessed for each treatment group.

  4. Safety as measured by fasting serum concentration of glucose [ Time Frame: Week 12, Week 24 ]
    Change from baseline to each of the scheduled study assessment time points for each treatment group.

  5. Safety as measured by fasting serum concentration of insulin [ Time Frame: Week 12, Week 24 ]
    Change from baseline to each of the scheduled study assessment time points for each treatment group.

  6. Efficacy as measured by concentration of serum pharmacodynamic biomarkers [ Time Frame: Week 12, Week 24 ]
    CD23 (also known as Fc epsilon RII) and Macrophage Derived Chemokine (MDC) and concentration from baseline to Week 24.

  7. Safety as measured by concentration of Salivary Cortisol [ Time Frame: Day 1, Week 12, Week 24 ]
    First-in-morning salivary cortisol levels will be measured. Cortisol measures falling below 3.6 µg/dL (or 100 nM) will be considered to be indicative of the development of adrenal suppression. Cortisol will be assessed for each treatment group.


Other Outcome Measures:
  1. Efficacy as measured by Time to Run/Walk Test (TTRW) [ Time Frame: Week 12, Week 24 ]
    Change from baseline to each of the scheduled assessment time points for each treatment group.

  2. Efficacy as measured by North Star Ambulatory Assessment (NSAA) score [ Time Frame: Week 12, Week 24 ]
    Change from baseline to each of the scheduled assessment time points for each treatment group.

  3. Tolerability as measured by NeuroQOL score [ Time Frame: 24 weeks ]
    Participants or participants' parent(s)/legal guardian(s) will be asked to complete the NeuroQOL scales for fatigue, upper and lower extremities function and sleep. Change from baseline to 24 weeks will be assessed by treatment group.



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:   18 Years to 64 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subject or 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;
  2. Subject is a male and has a confirmed diagnosis of Becker dystrophy as defined as:

    1. Identifiable mutation within the DMD gene (deletion/duplication of one or more exons), where reading frame can be predicted as 'in-frame', and clinical picture consistent with Becker dystrophy, OR
    2. Complete dystrophin gene sequencing showing an alteration (small mutation, duplication, other) that is expected to allow production of an internally deleted dystrophin protein, with a typical clinical picture of Becker dystrophy;
  3. Subject is ≥ 18 years of age and <65 years of age at time of informed consent;
  4. Subject is able to perform the timed run/walk 10 meters assessment (TTRW) in ≤ 30 sec at screening; assistive devices, cane or walker, are allowed.
  5. Subject has an NSAA score ≤ 32 at screening.
  6. 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). While AST and ALT can be elevated due to disease of muscle or liver, the study PI will review any increases of AST or ALT. If above upper limit of normal (ULN), then study PI will assess whether the increases are likely of muscle origin to determine inclusion.
  7. Subject has not received oral glucocorticoids or other oral immunosuppressive agents for at least 3 months prior to first administration of study medication. [Note: Inhaled and/or topical glucocorticoids are permitted if last use is at least 4 weeks prior to first administration of study medication or if administered at stable dose beginning at least 4 weeks prior to first administration of study medication and anticipated to be used at the stable dose regimen for the duration of the study];
  8. Subject has evidence of chicken pox immunity as determined by:

    1. 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
    2. Documentation, provided at the Screening Visit, that the subject has received 2 doses of varicella vaccine, with or without serologic evidence of immunity, with the second of the 2 immunizations given at least 14 days prior to first administration of study medication;
  9. Subject is willing and able to comply with scheduled visits, study medication administration plan, and study procedures.
  10. Subject agrees to use barrier contraception methods during his participation in this study and for 30 days after the tapering dose is completed.

Exclusion Criteria:

  1. Subject has current or history of major renal or hepatic impairment, uncontrolled diabetes mellitus (defined as a diagnosis of diabetes with random glucose more than 1.5x ULN at screening and the patient has symptoms of polyuria or polydipsia) 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), or mexrenone (mexrenoate potassium) within 4 weeks prior to administration of study medication;
  5. Subject has evidence of symptomatic cardiomyopathy [Note: Asymptomatic cardiac abnormality on investigation would not be exclusionary unless cardiac ejection fraction is less than 40%];
  6. Subject has an allergy or hypersensitivity to the study medication or to any of its constituents;
  7. Subject has severe behavioral or cognitive problems that preclude participation in the study, in the opinion of the Investigator;
  8. 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;
  9. Subject is taking (or has taken within 4 weeks prior to first dose of study medication) herbal remedies and supplements which can impact muscle strength and function (e.g., Co-enzyme Q10, creatine, etc);
  10. Subject has been administered a live attenuated vaccine within 14 days prior to the first dose of study medication;
  11. Subject is currently taking any other investigational drug or has taken any other investigational drug within 3 months prior to first dose of study medication; or
  12. Subject has previously been enrolled in the VBP15-BMD-001 study or any other vamorolone 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): NCT05166109


Contacts
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Contact: Eric P Hoffman, Ph.D. 301-762-7980 eric.hoffman@reveragen.com

Locations
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United States, Pennsylvania
University of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15261
Contact: Gabriela Niizawa    412-383-9775    niizawaga@upmc.edu   
Italy
Azienda Ospedale Universita Padova Recruiting
Padova, Italy, 35129
Contact: Elena Pegoraro, MD       elena.pegoraro@unipd.it   
Sponsors and Collaborators
ReveraGen BioPharma, Inc.
Santhera Pharmaceuticals
Investigators
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Study Chair: Paula Clemens, M.D. University of Pittsburgh
Publications:

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Responsible Party: ReveraGen BioPharma, Inc.
ClinicalTrials.gov Identifier: NCT05166109    
Other Study ID Numbers: VBP15-BMD-001
1R01FD007284-01 ( U.S. FDA Grant/Contract )
First Posted: December 21, 2021    Key Record Dates
Last Update Posted: April 4, 2024
Last Verified: April 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by ReveraGen BioPharma, Inc.:
Becker Muscular Dystrophy
Duchenne Muscular Dystrophy
Duchenne and Becker Muscular Dystrophy
Muscular Dystrophy
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