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
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. The study is comprised of a Pretreatment Screening Period of up to 5 weeks duration (unless extended to accommodate varicella vaccination), a 1-day Pretreatment Baseline Period, a 24-week Treatment Period, and a 4-week Dose-tapering Period (for subjects not continuing directly with further vamorolone treatment). Subjects will be enrolled into this study at the time written informed consent is given, and administered study medication only after completion of all Pretreatment Screening assessments to confirm eligibility. Subjects will be assessed for safety, tolerability, PK, PD, and effect on physical functioning at scheduled visits throughout the study. Screening assessments will be performed prior to baseline assessments on Day -1 and first administration of study medication on Day 1. After completion of Screening and Baseline assessments, subjects will return to the study clinic on Day 1 for safety, PK and PD assessments prior to administration of the first dose of study medication. Additional on-site study visits will occur at Week 4, Week 12, and Week 24. Adverse events, including serious adverse events (SAEs), and concomitant medications will be recorded throughout the study. A Data and Safety Monitoring Board (DSMB) will review SAEs and other pertinent safety data at regular intervals during the study, and make recommendations to the Sponsor and Study Team regarding study conduct. Subject diaries will be dispensed at the Day 1, Week 12, and Week 24 (for subjects participating in the Dose-tapering Period) Visits to record AEs, changes to concomitant medications taken during the study, and any missed or incomplete doses of study medication. The scheduled Week 12 and Week 24 assessments may be performed over a 2-day period, if necessary, to facilitate scheduling. Subjects who complete the VBP15-BMD-001 study assessments through the Week 24 Visit may be given the opportunity to continue to receive vamorolone as part of an expanded access or compassionate use program. Subjects who complete the VBP15-BMD-001 study and will enroll directly into an expanded access or compassionate use program to continue vamorolone treatment will be discharged from the VBP15-BMD-001 study following completion of all Week 24 assessments. Subjects who will not continue vamorolone treatment in the expanded access or compassionate use program will have their study medication dose tapered during a 4-week Dose-tapering Period to taper study medication prior to discharge from the study. For these subjects, site study staff will contact the subject or parent(s)/guardian(s) by telephone at Week 26 to ensure that the dose tapering is proceeding according to protocol, to assess potential signs or symptoms of adrenal suppression, and to address any questions the subject or parent(s)/guardian(s) may have. In the event that any clinical or laboratory parameters remain abnormal at the time of discharge from the study, the subject will be followed medically, as clinically indicated. Any subject who discontinues the study prior to the Week 24 Visit should return to the study unit for scheduled Week 24 assessments at the time of early withdrawal and a Week 28 Visit following the taper, whenever possible, assuming the subject has not withdrawn consent. Any subject who withdraws early from the study after study medication dosing has begun should undergo dose-tapering following early completion of the Week 24 assessments and a Week 28 Visit following the taper.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
46
Vamorolone 4.0% wt/wt oral suspension will be administered for the duration of the study.
Placebo to Vamorolone 4.0% wt/wt oral suspension will be administered for the duration of the study.
University of Pittsburgh
Pittsburgh, Pennsylvania, United States
Azienda Ospedale Universita Padova
Padova, Italy
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE Version 5.0
Clinical AEs and clinical laboratory AEs will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0 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
Time frame: 24 weeks
Total Number of Adverse Events as Assessed by CTCAE Version 5.0
Clinical AEs and clinical laboratory AEs will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0 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
Time frame: 24 weeks
Pharmacokinetics as Measured by Cmax
Blood will be collected from all subjects at the Day 1 Visit, at 1, 2 and 3 hours post-dose, for vamorolone PK analysis
Time frame: Day 1
Pharmacokinetics as Measured by Tmax
Blood will be collected from all subjects at the Day 1 Visit, at 1, 2 and 3 hours post-dose, for vamorolone PK analysis
Time frame: Day 1
Pharmacokinetics as Measured by Dose-normalized Cmax
Blood will be collected from all subjects at the Day 1 Visit, at 1, 2 and 3 hours post-dose, for vamorolone PK analysis
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Time frame: Day 1
Safety as Measured by Serum Concentration of Osteocalcin
Change from baseline to Week 24 will be assessed for each treatment group.
Time frame: Week 24
Safety as Measured by Serum Concentration of Hemoglobin A1c (HbA1c)
Change from baseline to Week 24 will be assessed for each treatment group.
Time frame: Week 24
Safety as Measured by Fasting Serum Concentration of Glucose
Change from baseline to week 24 for each treatment group.
Time frame: Week 24
Safety as Measured by Fasting Serum Concentration of Insulin
Change from baseline to week 24 for each treatment group.
Time frame: Week 24
Safety as Measured by Concentration of Salivary Cortisol
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.
Time frame: Week 24
Efficacy as Measured by Concentration of Serum Pharmacodynamic Biomarkers (CD23)
CD23 (also known as Fc epsilon RII) concentration at Week 24.
Time frame: Week 24
Efficacy as Measured by Concentration of Serum Pharmacodynamic Biomarkers (MDC)
MDC (macrophage-derived chemokine) concentration at Week 24.
Time frame: Week 24
Efficacy as Measured by Time to Run/Walk Velocity (TTRWV)
Change from baseline to week 24 for each treatment group.
Time frame: Week 24
Efficacy as Measured by North Star Ambulatory Assessment (NSAA) Score
North Star Ambulatory Assessment (NSAA). The assessment's score can range from 0 to 34. Higher scores indicate a better outcome assessing functional mobility. Data is presented as change from baseline to week 24 for each treatment group.
Time frame: Week 24