Duchenne Muscular Dystrophy
Conditions
Keywords
Duchenne muscular dystrophy, vamorolone
Brief summary
This long-term extension study is an open-label, multiple-dose study to evaluate the long-term safety, tolerability, efficacy and PD of vamorolone administered once daily by liquid oral suspension over a Treatment Period of 24 months to young boys with DMD who participated in the VBP15-002 Phase IIa and VBP15-003 Phase IIa extension core studies.
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 months.
Interventions
Oral administration of 0.25 mg/kg/day daily for 24 months.
Oral administration of 0.75 mg/kg/day daily for 24 months.
Oral administration of 2.0 mg/kg/day daily for 24 months.
Oral administration of 6.0 mg/kg/day daily for 24 months.
Sponsors
University of Pittsburgh
Cooperative International Neuromuscular Research Group
ReveraGen BioPharma, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
4 Years to 7 Years
Healthy volunteers
No
Inclusion criteria
1. Subject's parent or legal guardian has provided written informed consent and HIPAA authorization (if applicable) prior to any VBP15-LTE long-term extension study-specific procedures; 2. Subject has previously completed study VBP15-003 up to and including the Week 24 Final assessments, prior to enrolling in the VBP15-LTE study at the conclusion of the VBP15-003 Week 24 Visit \[Note: if entering the dose-tapering period, subject is enrolling within 8 weeks after the VBP15-003 final visit following dose-tapering\]; and 3. Subject and parent/guardian are willing and able to comply with scheduled visits, study drug administration plan, and study procedures.
Exclusion criteria
1. Subject had a serious or severe adverse event in study VBP15-003 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 long-term extension study; 2. Subject has current or history of major renal or hepatic impairment, diabetes mellitus or immunosuppression; 3. Subject has current or history of chronic systemic fungal or viral infections; 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 \[Notes: Past transient use of oral glucocorticoids or other oral immunosuppressive agents for no longer than 3 months cumulative, with last use at least 3 months prior to first dose of study medication, will be considered for eligibility on a case-by-case basis. Inhaled and/or topical glucocorticoids prescribed for an indication other than DMD are permitted but must be administered at stable dose for at least 3 months prior to study drug administration\]; 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 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: Subjects may be re-evaluated if ineligible due to a transient condition which would prevent the subject from participating.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE Version 4.03 | 24 months | 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- month Treatment Period, in boys ages 4-7 years with DMD; 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); |
| Total Number of Adverse Events as Assessed by CTCAE Version 4.03 | 24 Months | 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-month Treatment Period, in boys ages 4-7 years with DMD. 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). |
Countries
Australia, Canada, Israel, Sweden, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dose Level Group 1 Participants enrolled in Dose Level Group 1 will receive vamorolone 0.25 mg/kg/day.
Vamorolone 0.25 mg/day/day: Oral administration of 0.25 mg/kg/day daily | 11 |
| Dose Level Group 2 Participants enrolled in Dose Level Group 2 will receive vamorolone 0.75 mg/kg/day.
Vamorolone 0.75 mg/day/day: Oral administration of 0.75 mg/kg/day daily | 12 |
| Dose Level Group 3 Participants enrolled in Dose Level Group 3 will receive vamorolone 2.0 mg/kg/day.
Vamorolone 2.0 mg/day/day: Oral administration of 2.0 mg/kg/day daily | 12 |
| Dose Level Group 4 Participants enrolled in Dose Level Group 4 will receive vamorolone 6.0 mg/kg/day.
Vamorolone 6.0 mg/day/day: Oral administration of 6.0 mg/kg/day daily | 11 |
| Total | 46 |
Baseline characteristics
| Characteristic | Dose Level Group 1 | Dose Level Group 2 | Dose Level Group 3 | Dose Level Group 4 | Total |
|---|---|---|---|---|---|
| Age, Continuous | 5.87 years STANDARD_DEVIATION 1.135 | 5.11 years STANDARD_DEVIATION 0.805 | 5.13 years STANDARD_DEVIATION 0.964 | 5.27 years STANDARD_DEVIATION 0.856 | 5.33 years STANDARD_DEVIATION 0.965 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 3 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 11 Participants | 12 Participants | 8 Participants | 42 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 10 Participants | 10 Participants | 12 Participants | 11 Participants | 43 Participants |
| Region of Enrollment Australia | 0 participants | 2 participants | 2 participants | 2 participants | 6 participants |
| Region of Enrollment Canada | 3 participants | 0 participants | 2 participants | 2 participants | 7 participants |
| Region of Enrollment Israel | 0 participants | 3 participants | 2 participants | 0 participants | 5 participants |
| Region of Enrollment Sweden | 0 participants | 4 participants | 0 participants | 0 participants | 4 participants |
| Region of Enrollment United Kingdom | 0 participants | 0 participants | 4 participants | 2 participants | 6 participants |
| Region of Enrollment United States | 8 participants | 3 participants | 2 participants | 5 participants | 18 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 11 Participants | 12 Participants | 12 Participants | 11 Participants | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 23 | 0 / 38 | 0 / 3 | 0 / 41 |
| other Total, other adverse events | 4 / 11 | 14 / 23 | 29 / 38 | 1 / 3 | 39 / 41 |
| serious Total, serious adverse events | 0 / 11 | 1 / 23 | 0 / 38 | 0 / 3 | 1 / 41 |
Outcome results
Primary
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE Version 4.03
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- month Treatment Period, in boys ages 4-7 years with DMD; 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);
Time frame: 24 months
Population: All subjects who receive at least one dose of vamorolone study medication in the study will be included in the Safety Population. The Safety Population is the primary analysis population for safety assessments.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Level Group 1 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE Version 4.03 | 4 Participants |
| Dose Level Group 2 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE Version 4.03 | 14 Participants |
| Dose Level Group 3 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE Version 4.03 | 29 Participants |
| Dose Level Group 4 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE Version 4.03 | 1 Participants |
| Dose Level Group 5 | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE Version 4.03 | 39 Participants |
Primary
Total Number of Adverse Events as Assessed by CTCAE Version 4.03
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-month Treatment Period, in boys ages 4-7 years with DMD. 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).
Time frame: 24 Months
Population: All subjects who receive at least one dose of vamorolone study medication in the study will be included in the Safety Population. The Safety Population is the primary analysis population for safety assessments.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dose Level Group 1 | Total Number of Adverse Events as Assessed by CTCAE Version 4.03 | Total Number of AEs | 15 Events |
| Dose Level Group 1 | Total Number of Adverse Events as Assessed by CTCAE Version 4.03 | Total Number of TEAEs | 14 Events |
| Dose Level Group 2 | Total Number of Adverse Events as Assessed by CTCAE Version 4.03 | Total Number of AEs | 34 Events |
| Dose Level Group 2 | Total Number of Adverse Events as Assessed by CTCAE Version 4.03 | Total Number of TEAEs | 34 Events |
| Dose Level Group 3 | Total Number of Adverse Events as Assessed by CTCAE Version 4.03 | Total Number of AEs | 203 Events |
| Dose Level Group 3 | Total Number of Adverse Events as Assessed by CTCAE Version 4.03 | Total Number of TEAEs | 202 Events |
| Dose Level Group 4 | Total Number of Adverse Events as Assessed by CTCAE Version 4.03 | Total Number of TEAEs | 5 Events |
| Dose Level Group 4 | Total Number of Adverse Events as Assessed by CTCAE Version 4.03 | Total Number of AEs | 5 Events |
| Dose Level Group 5 | Total Number of Adverse Events as Assessed by CTCAE Version 4.03 | Total Number of AEs | 302 Events |
| Dose Level Group 5 | Total Number of Adverse Events as Assessed by CTCAE Version 4.03 | Total Number of TEAEs | 300 Events |