Duchenne Muscular Dystrophy
Conditions
Keywords
Duchenne muscular dystrophy, vamorolone
Brief summary
The main purposes of this study are to see if it is safe to use a new medication called vamorolone for more than two weeks in children with Duchenne muscular dystrophy (DMD), to see if vamorolone works for the treatment for DMD, and to see how any potential side effects compare to those seen in boys using steroids.
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 weeks.
Interventions
Oral administration of 0.25 mg/kg/day daily for 24 weeks.
Oral administration of 0.75 mg/kg/day daily for 24 weeks.
Oral administration of 2.0 mg/kg/day daily for 24 weeks.
Oral administration of 6.0 mg/kg/day daily for 24 weeks.
Sponsors
University of Pittsburgh
National Institute of Neurological Disorders and Stroke (NINDS)
Cooperative International Neuromuscular Research Group
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
ReveraGen BioPharma, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
4 Years to 7 Years
Healthy volunteers
No
Inclusion criteria
1. Participant's parent or legal guardian has provided written informed consent/HIPAA authorization prior to any extension study-specific procedures; 2. Participant has previously completed study VBP15-002 up to and including the Week 4 Follow-up assessments within 8 weeks prior to enrollment; and 3. Participant and parent/guardian are willing and able to comply with scheduled visits, study drug administration plan, and study procedures.
Exclusion criteria
1. 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; 2. Participant has current or history of major renal or hepatic impairment, diabetes mellitus or immunosuppression; 3. Participant has current or history of chronic systemic fungal or viral infections; 4. 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; 5. Participant has evidence of symptomatic cardiomyopathy. \[Note: Asymptomatic cardiac abnormality on investigation would not be exclusionary\]; 6. Participant is currently being treated or has received previous treatment with oral glucocorticoids or other immunosuppressive agents. \[Notes: Past transient use of oral glucocorticoids or other oral immunosuppressive agents for no longer than 3 months cumulative, with last use at least 3 months prior to first dose of study medication, will be considered for eligibility on a case-by-case basis. Inhaled and/or topical corticosteroids prescribed for an indication other than DMD are permitted but must be administered at stable dose for at least 3 months prior to study drug administration\]; 7. Subject has used idebenone within 4 weeks prior to the first dose of study medication; 8. Participant has an allergy or hypersensitivity to the study medication or to any of its constituents; 9. Participant has severe behavioral or cognitive problems that preclude participation in the study, in the opinion of the Investigator; 10. 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 11. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events as Assessed by CTCAE Version 4.03 | 24 weeks | 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. |
| Total Number of Adverse Events as Assessed by CTCAE Version 4.03 | 24 weeks | 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. |
| Muscle Function Measured by Time to Stand Test (TTSTAND)- Velocity | 002 Baseline, 003 Baseline, 003 Week 12, Week 24 (Note: 002 Baseline is from VBP15-002 4 week study (NCT02760264), previous to VBP15-003) | 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 |
| BMI Z-score | 002 Baseline, 003 Week 12, Week 24 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Pharmacodynamics Biomarkers Measured by Levels of Osteocalcin | 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) | 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. |
| Serum Pharmacodynamics Biomarkers Measured by Levels of P1NP | 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) | 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. |
| Serum Pharmacodynamics Biomarkers Measured by Levels of CTX | 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) | 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. |
| Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c | 002 Baseline, 003 Week 8, 003 Week 16, 003 Week 24, 003 Week 26-29 | 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. |
| Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Run/Walk 10 Meters Test (TTRW)- Velocity | 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) | 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. |
| Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by North Star Ambulatory Assessment (NSAA) | 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) | 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. |
| Muscle Strength, Mobility, and Functional Exercise Capacity vs. Historical Controls as Measured by 6-minute Walk Test (6MWT) Meters | 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) | 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. |
| Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Climb Test (TTCLIMB)- Velocity | 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) | 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. |
| Serum Pharmacodynamics Biomarkers Measured by Levels of ACTH | 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) | 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. |
| Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Glucose | 002 Baseline, 003 Week 12, 003 Week 24 | 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. |
| Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Insulin | 002 Baseline, 003 Week 12, 003 Week 24 | 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. |
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 for 24 weeks. | 12 |
| 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 for 24 weeks. | 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 for 24 weeks. | 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 for 24 weeks. | 12 |
| Total | 48 |
Baseline characteristics
| Characteristic | Total | Dose Level Group 1 | Dose Level Group 2 | Dose Level Group 3 | Dose Level Group 4 |
|---|---|---|---|---|---|
| Age, Customized Age | 4.9 years STANDARD_DEVIATION 0.87 | 5.2 years STANDARD_DEVIATION 1.03 | 4.8 years STANDARD_DEVIATION 0.83 | 4.7 years STANDARD_DEVIATION 0.89 | 4.8 years STANDARD_DEVIATION 0.75 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 44 Participants | 12 Participants | 11 Participants | 12 Participants | 9 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 | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 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 | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 45 Participants | 11 Participants | 10 Participants | 12 Participants | 12 Participants |
| Region of Enrollment Australia | 6 participants | 0 participants | 2 participants | 2 participants | 2 participants |
| Region of Enrollment Canada | 7 participants | 3 participants | 0 participants | 2 participants | 2 participants |
| Region of Enrollment Israel | 5 participants | 0 participants | 3 participants | 2 participants | 0 participants |
| Region of Enrollment Sweden | 4 participants | 0 participants | 4 participants | 0 participants | 0 participants |
| Region of Enrollment United Kingdom | 6 participants | 0 participants | 0 participants | 4 participants | 2 participants |
| Region of Enrollment United States | 20 participants | 9 participants | 3 participants | 2 participants | 6 participants |
| Sex/Gender, Customized Male | 48 Participants | 12 Participants | 12 Participants | 12 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 10 / 12 | 10 / 12 | 11 / 12 | 11 / 12 |
| serious Total, serious adverse events | 0 / 12 | 1 / 12 | 0 / 12 | 2 / 12 |
Outcome results
Primary
BMI Z-score
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.
Time frame: 002 Baseline, 003 Week 12, Week 24
Population: All subjects who receive at least one dose of vamorolone study medication in the extension study will be included in the Safety Population. The Safety Population is the primary analysis population for safety assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Level Group 1 | BMI Z-score | 003 Week 24 Change from 002 Baseline | -0.161 z score | Standard Deviation 0.3234 |
| Dose Level Group 1 | BMI Z-score | 003 Week 24 | 1.004 z score | Standard Deviation 0.6381 |
| Dose Level Group 1 | BMI Z-score | 003 Week 12 | 1.103 z score | Standard Deviation 0.6457 |
| Dose Level Group 1 | BMI Z-score | 003 Week 12 Change from 002 Baseline | -0.062 z score | Standard Deviation 0.2438 |
| Dose Level Group 1 | BMI Z-score | 002 Baseline | 1.165 z score | Standard Deviation 0.6219 |
| Dose Level Group 2 | BMI Z-score | 003 Week 12 Change from 002 Baseline | -0.209 z score | Standard Deviation 0.4078 |
| Dose Level Group 2 | BMI Z-score | 003 Week 24 Change from 002 Baseline | -0.210 z score | Standard Deviation 0.3629 |
| Dose Level Group 2 | BMI Z-score | 003 Week 12 | 0.494 z score | Standard Deviation 1.068 |
| Dose Level Group 2 | BMI Z-score | 002 Baseline | 0.703 z score | Standard Deviation 1.0738 |
| Dose Level Group 2 | BMI Z-score | 003 Week 24 | 0.493 z score | Standard Deviation 1.1696 |
| Dose Level Group 3 | BMI Z-score | 003 Week 24 | 1.242 z score | Standard Deviation 0.4596 |
| Dose Level Group 3 | BMI Z-score | 002 Baseline | 1.200 z score | Standard Deviation 0.5325 |
| Dose Level Group 3 | BMI Z-score | 003 Week 12 | 1.261 z score | Standard Deviation 0.3981 |
| Dose Level Group 3 | BMI Z-score | 003 Week 12 Change from 002 Baseline | 0.062 z score | Standard Deviation 0.3886 |
| Dose Level Group 3 | BMI Z-score | 003 Week 24 Change from 002 Baseline | 0.043 z score | Standard Deviation 0.3849 |
| Dose Level Group 4 | BMI Z-score | 003 Week 24 Change from 002 Baseline | 0.493 z score | Standard Deviation 0.6363 |
| Dose Level Group 4 | BMI Z-score | 003 Week 12 Change from 002 Baseline | 0.174 z score | Standard Deviation 0.5826 |
| Dose Level Group 4 | BMI Z-score | 003 Week 24 | 1.330 z score | Standard Deviation 0.5857 |
| Dose Level Group 4 | BMI Z-score | 003 Week 12 | 1.011 z score | Standard Deviation 0.7034 |
| Dose Level Group 4 | BMI Z-score | 002 Baseline | 0.695 z score | Standard Deviation 0.7189 |
Primary
Muscle Function Measured by Time to Stand Test (TTSTAND)- Velocity
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
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)
Population: All subjects who receive at least one dose of vamorolone study medication in the extension study will be included in the Safety Population. The Safety Population is the primary analysis population for safety assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Level Group 1 | Muscle Function Measured by Time to Stand Test (TTSTAND)- Velocity | 002 Baseline | 0.18 Rises/Second | Standard Deviation 0.065 |
| Dose Level Group 1 | Muscle Function Measured by Time to Stand Test (TTSTAND)- Velocity | 003 Week 12 Change from 002 Baseline | -0.01 Rises/Second | Standard Deviation 0.061 |
| Dose Level Group 1 | Muscle Function Measured by Time to Stand Test (TTSTAND)- Velocity | 003 Week 24 | 0.18 Rises/Second | Standard Deviation 0.081 |
| Dose Level Group 1 | Muscle Function Measured by Time to Stand Test (TTSTAND)- Velocity | 003 Week 12 | 0.18 Rises/Second | Standard Deviation 0.072 |
| Dose Level Group 1 | Muscle Function Measured by Time to Stand Test (TTSTAND)- Velocity | 003 Baseline | 0.15 Rises/Second | Standard Deviation 0.045 |
| Dose Level Group 1 | Muscle Function Measured by Time to Stand Test (TTSTAND)- Velocity | 003 Week 24 Change from 002 Baseline | -0.01 Rises/Second | Standard Deviation 0.066 |
| Dose Level Group 2 | Muscle Function Measured by Time to Stand Test (TTSTAND)- Velocity | 003 Week 12 | 0.23 Rises/Second | Standard Deviation 0.102 |
| Dose Level Group 2 | Muscle Function Measured by Time to Stand Test (TTSTAND)- Velocity | 003 Week 24 | 0.24 Rises/Second | Standard Deviation 0.114 |
| Dose Level Group 2 | Muscle Function Measured by Time to Stand Test (TTSTAND)- Velocity | 003 Week 24 Change from 002 Baseline | 0.00 Rises/Second | Standard Deviation 0.062 |
| Dose Level Group 2 | Muscle Function Measured by Time to Stand Test (TTSTAND)- Velocity | 003 Week 12 Change from 002 Baseline | 0.00 Rises/Second | Standard Deviation 0.054 |
| Dose Level Group 2 | Muscle Function Measured by Time to Stand Test (TTSTAND)- Velocity | 003 Baseline | 0.22 Rises/Second | Standard Deviation 0.077 |
| Dose Level Group 2 | Muscle Function Measured by Time to Stand Test (TTSTAND)- Velocity | 002 Baseline | 0.24 Rises/Second | Standard Deviation 0.09 |
| Dose Level Group 3 | Muscle Function Measured by Time to Stand Test (TTSTAND)- Velocity | 003 Week 24 Change from 002 Baseline | 0.05 Rises/Second | Standard Deviation 0.061 |
| Dose Level Group 3 | Muscle Function Measured by Time to Stand Test (TTSTAND)- Velocity | 003 Week 12 Change from 002 Baseline | 0.02 Rises/Second | Standard Deviation 0.066 |
| Dose Level Group 3 | Muscle Function Measured by Time to Stand Test (TTSTAND)- Velocity | 002 Baseline | 0.22 Rises/Second | Standard Deviation 0.082 |
| Dose Level Group 3 | Muscle Function Measured by Time to Stand Test (TTSTAND)- Velocity | 003 Baseline | 0.24 Rises/Second | Standard Deviation 0.078 |
| Dose Level Group 3 | Muscle Function Measured by Time to Stand Test (TTSTAND)- Velocity | 003 Week 12 | 0.24 Rises/Second | Standard Deviation 0.089 |
| Dose Level Group 3 | Muscle Function Measured by Time to Stand Test (TTSTAND)- Velocity | 003 Week 24 | 0.26 Rises/Second | Standard Deviation 0.108 |
| Dose Level Group 4 | Muscle Function Measured by Time to Stand Test (TTSTAND)- Velocity | 003 Week 12 | 0.22 Rises/Second | Standard Deviation 0.075 |
| Dose Level Group 4 | Muscle Function Measured by Time to Stand Test (TTSTAND)- Velocity | 003 Week 24 Change from 002 Baseline | 0.04 Rises/Second | Standard Deviation 0.045 |
| Dose Level Group 4 | Muscle Function Measured by Time to Stand Test (TTSTAND)- Velocity | 003 Week 24 | 0.24 Rises/Second | Standard Deviation 0.086 |
| Dose Level Group 4 | Muscle Function Measured by Time to Stand Test (TTSTAND)- Velocity | 003 Baseline | 0.22 Rises/Second | Standard Deviation 0.07 |
| Dose Level Group 4 | Muscle Function Measured by Time to Stand Test (TTSTAND)- Velocity | 002 Baseline | 0.19 Rises/Second | Standard Deviation 0.056 |
| Dose Level Group 4 | Muscle Function Measured by Time to Stand Test (TTSTAND)- Velocity | 003 Week 12 Change from 002 Baseline | 0.02 Rises/Second | Standard Deviation 0.034 |
Primary
Number of Participants With Adverse Events as Assessed by CTCAE Version 4.03
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.
Time frame: 24 weeks
Population: All subjects who receive at least one dose of vamorolone study medication in the extension 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 | Number of Participants With Adverse Events as Assessed by CTCAE Version 4.03 | Discontinuation of Study Drug due to TEAE | 0 participants |
| Dose Level Group 1 | Number of Participants With Adverse Events as Assessed by CTCAE Version 4.03 | Subjects with Any TEAE | 10 participants |
| Dose Level Group 1 | Number of Participants With Adverse Events as Assessed by CTCAE Version 4.03 | Subjects with Any CTCAE Grade 3 or Higher TEAE | 0 participants |
| Dose Level Group 1 | Number of Participants With Adverse Events as Assessed by CTCAE Version 4.03 | Subjects with Any Serious TEAE | 0 participants |
| Dose Level Group 1 | Number of Participants With Adverse Events as Assessed by CTCAE Version 4.03 | Subjects with Any Drug Related TEAE | 1 participants |
| Dose Level Group 1 | Number of Participants With Adverse Events as Assessed by CTCAE Version 4.03 | Death | 0 participants |
| Dose Level Group 2 | Number of Participants With Adverse Events as Assessed by CTCAE Version 4.03 | Subjects with Any Serious TEAE | 1 participants |
| Dose Level Group 2 | Number of Participants With Adverse Events as Assessed by CTCAE Version 4.03 | Subjects with Any CTCAE Grade 3 or Higher TEAE | 0 participants |
| Dose Level Group 2 | Number of Participants With Adverse Events as Assessed by CTCAE Version 4.03 | Subjects with Any TEAE | 10 participants |
| Dose Level Group 2 | Number of Participants With Adverse Events as Assessed by CTCAE Version 4.03 | Subjects with Any Drug Related TEAE | 2 participants |
| Dose Level Group 2 | Number of Participants With Adverse Events as Assessed by CTCAE Version 4.03 | Death | 0 participants |
| Dose Level Group 2 | Number of Participants With Adverse Events as Assessed by CTCAE Version 4.03 | Discontinuation of Study Drug due to TEAE | 0 participants |
| Dose Level Group 3 | Number of Participants With Adverse Events as Assessed by CTCAE Version 4.03 | Subjects with Any TEAE | 11 participants |
| Dose Level Group 3 | Number of Participants With Adverse Events as Assessed by CTCAE Version 4.03 | Subjects with Any Drug Related TEAE | 4 participants |
| Dose Level Group 3 | Number of Participants With Adverse Events as Assessed by CTCAE Version 4.03 | Subjects with Any Serious TEAE | 0 participants |
| Dose Level Group 3 | Number of Participants With Adverse Events as Assessed by CTCAE Version 4.03 | Subjects with Any CTCAE Grade 3 or Higher TEAE | 0 participants |
| Dose Level Group 3 | Number of Participants With Adverse Events as Assessed by CTCAE Version 4.03 | Discontinuation of Study Drug due to TEAE | 0 participants |
| Dose Level Group 3 | Number of Participants With Adverse Events as Assessed by CTCAE Version 4.03 | Death | 0 participants |
| Dose Level Group 4 | Number of Participants With Adverse Events as Assessed by CTCAE Version 4.03 | Subjects with Any Drug Related TEAE | 5 participants |
| Dose Level Group 4 | Number of Participants With Adverse Events as Assessed by CTCAE Version 4.03 | Death | 0 participants |
| Dose Level Group 4 | Number of Participants With Adverse Events as Assessed by CTCAE Version 4.03 | Discontinuation of Study Drug due to TEAE | 0 participants |
| Dose Level Group 4 | Number of Participants With Adverse Events as Assessed by CTCAE Version 4.03 | Subjects with Any TEAE | 11 participants |
| Dose Level Group 4 | Number of Participants With Adverse Events as Assessed by CTCAE Version 4.03 | Subjects with Any CTCAE Grade 3 or Higher TEAE | 2 participants |
| Dose Level Group 4 | Number of Participants With Adverse Events as Assessed by CTCAE Version 4.03 | Subjects with Any Serious TEAE | 2 participants |
Primary
Total Number of Adverse Events as Assessed by CTCAE Version 4.03
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.
Time frame: 24 weeks
Population: All subjects who receive at least one dose of vamorolone study medication in the extension 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 | 48 Events |
| Dose Level Group 1 | Total Number of Adverse Events as Assessed by CTCAE Version 4.03 | Total Number of TEAEs | 48 Events |
| Dose Level Group 2 | Total Number of Adverse Events as Assessed by CTCAE Version 4.03 | Total Number of TEAEs | 44 Events |
| Dose Level Group 2 | Total Number of Adverse Events as Assessed by CTCAE Version 4.03 | Total Number of AEs | 44 Events |
| Dose Level Group 3 | Total Number of Adverse Events as Assessed by CTCAE Version 4.03 | Total Number of AEs | 54 Events |
| Dose Level Group 3 | Total Number of Adverse Events as Assessed by CTCAE Version 4.03 | Total Number of TEAEs | 54 Events |
| Dose Level Group 4 | Total Number of Adverse Events as Assessed by CTCAE Version 4.03 | Total Number of AEs | 73 Events |
| Dose Level Group 4 | Total Number of Adverse Events as Assessed by CTCAE Version 4.03 | Total Number of TEAEs | 72 Events |
Secondary
Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by North Star Ambulatory Assessment (NSAA)
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.
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)
Population: All subjects who receive at least one dose of vamorolone study medication in the extension study will be included in the Safety Population. The Safety Population is the primary analysis population for safety assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Level Group 1 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by North Star Ambulatory Assessment (NSAA) | 002 Baseline | 19.0 scores on a scale | Standard Deviation 5.13 |
| Dose Level Group 1 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by North Star Ambulatory Assessment (NSAA) | 003 Baseline | 20.1 scores on a scale | Standard Deviation 7.3 |
| Dose Level Group 1 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by North Star Ambulatory Assessment (NSAA) | 003 Week 12 | 19.3 scores on a scale | Standard Deviation 5.6 |
| Dose Level Group 1 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by North Star Ambulatory Assessment (NSAA) | 003 Week 12 Change from 002 Baseline | 0.3 scores on a scale | Standard Deviation 2.06 |
| Dose Level Group 1 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by North Star Ambulatory Assessment (NSAA) | 003 Week 24 | 19.8 scores on a scale | Standard Deviation 7.09 |
| Dose Level Group 1 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by North Star Ambulatory Assessment (NSAA) | 003 Week 24 Change from 002 Baseline | 0.8 scores on a scale | Standard Deviation 2.83 |
| Dose Level Group 2 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by North Star Ambulatory Assessment (NSAA) | 003 Week 24 Change from 002 Baseline | 1.1 scores on a scale | Standard Deviation 2.94 |
| Dose Level Group 2 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by North Star Ambulatory Assessment (NSAA) | 003 Week 12 Change from 002 Baseline | 0.7 scores on a scale | Standard Deviation 2.71 |
| Dose Level Group 2 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by North Star Ambulatory Assessment (NSAA) | 002 Baseline | 20.5 scores on a scale | Standard Deviation 5.58 |
| Dose Level Group 2 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by North Star Ambulatory Assessment (NSAA) | 003 Week 12 | 21.2 scores on a scale | Standard Deviation 6.45 |
| Dose Level Group 2 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by North Star Ambulatory Assessment (NSAA) | 003 Baseline | 20.8 scores on a scale | Standard Deviation 5.66 |
| Dose Level Group 2 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by North Star Ambulatory Assessment (NSAA) | 003 Week 24 | 21.6 scores on a scale | Standard Deviation 7.23 |
| Dose Level Group 3 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by North Star Ambulatory Assessment (NSAA) | 003 Baseline | 21.7 scores on a scale | Standard Deviation 3.87 |
| Dose Level Group 3 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by North Star Ambulatory Assessment (NSAA) | 003 Week 12 | 21.0 scores on a scale | Standard Deviation 5.13 |
| Dose Level Group 3 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by North Star Ambulatory Assessment (NSAA) | 003 Week 12 Change from 002 Baseline | 1.0 scores on a scale | Standard Deviation 2.56 |
| Dose Level Group 3 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by North Star Ambulatory Assessment (NSAA) | 003 Week 24 Change from 002 Baseline | 2.3 scores on a scale | Standard Deviation 1.78 |
| Dose Level Group 3 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by North Star Ambulatory Assessment (NSAA) | 003 Week 24 | 22.3 scores on a scale | Standard Deviation 3.8 |
| Dose Level Group 3 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by North Star Ambulatory Assessment (NSAA) | 002 Baseline | 20.0 scores on a scale | Standard Deviation 4.95 |
| Dose Level Group 4 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by North Star Ambulatory Assessment (NSAA) | 003 Week 24 | 22.3 scores on a scale | Standard Deviation 5.76 |
| Dose Level Group 4 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by North Star Ambulatory Assessment (NSAA) | 003 Week 24 Change from 002 Baseline | 2.5 scores on a scale | Standard Deviation 2.62 |
| Dose Level Group 4 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by North Star Ambulatory Assessment (NSAA) | 003 Baseline | 20.4 scores on a scale | Standard Deviation 4.01 |
| Dose Level Group 4 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by North Star Ambulatory Assessment (NSAA) | 003 Week 12 Change from 002 Baseline | 0.5 scores on a scale | Standard Deviation 2.38 |
| Dose Level Group 4 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by North Star Ambulatory Assessment (NSAA) | 002 Baseline | 19.7 scores on a scale | Standard Deviation 4.94 |
| Dose Level Group 4 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by North Star Ambulatory Assessment (NSAA) | 003 Week 12 | 20.4 scores on a scale | Standard Deviation 5.41 |
Secondary
Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Climb Test (TTCLIMB)- Velocity
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.
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)
Population: All subjects who receive at least one dose of vamorolone study medication in the extension study will be included in the Safety Population. The Safety Population is the primary analysis population for safety assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Level Group 1 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Climb Test (TTCLIMB)- Velocity | 002 Baseline | 0.20 tasks/ second | Standard Deviation 0.054 |
| Dose Level Group 1 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Climb Test (TTCLIMB)- Velocity | 003 Baseline | 0.20 tasks/ second | Standard Deviation 0.065 |
| Dose Level Group 1 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Climb Test (TTCLIMB)- Velocity | 003 Week 12 | 0.21 tasks/ second | Standard Deviation 0.064 |
| Dose Level Group 1 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Climb Test (TTCLIMB)- Velocity | 003 Week 12 Change from 002 Baseline | 0.01 tasks/ second | Standard Deviation 0.044 |
| Dose Level Group 1 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Climb Test (TTCLIMB)- Velocity | 003 Week 24 | 0.20 tasks/ second | Standard Deviation 0.071 |
| Dose Level Group 1 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Climb Test (TTCLIMB)- Velocity | 003 Week 24 Change from 002 Baseline | 0.00 tasks/ second | Standard Deviation 0.076 |
| Dose Level Group 2 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Climb Test (TTCLIMB)- Velocity | 003 Week 24 Change from 002 Baseline | 0.01 tasks/ second | Standard Deviation 0.066 |
| Dose Level Group 2 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Climb Test (TTCLIMB)- Velocity | 003 Week 12 Change from 002 Baseline | 0.05 tasks/ second | Standard Deviation 0.115 |
| Dose Level Group 2 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Climb Test (TTCLIMB)- Velocity | 002 Baseline | 0.29 tasks/ second | Standard Deviation 0.147 |
| Dose Level Group 2 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Climb Test (TTCLIMB)- Velocity | 003 Week 12 | 0.34 tasks/ second | Standard Deviation 0.238 |
| Dose Level Group 2 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Climb Test (TTCLIMB)- Velocity | 003 Baseline | 0.29 tasks/ second | Standard Deviation 0.168 |
| Dose Level Group 2 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Climb Test (TTCLIMB)- Velocity | 003 Week 24 | 0.30 tasks/ second | Standard Deviation 0.166 |
| Dose Level Group 3 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Climb Test (TTCLIMB)- Velocity | 003 Baseline | 0.31 tasks/ second | Standard Deviation 0.144 |
| Dose Level Group 3 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Climb Test (TTCLIMB)- Velocity | 003 Week 12 | 0.31 tasks/ second | Standard Deviation 0.157 |
| Dose Level Group 3 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Climb Test (TTCLIMB)- Velocity | 003 Week 12 Change from 002 Baseline | 0.02 tasks/ second | Standard Deviation 0.107 |
| Dose Level Group 3 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Climb Test (TTCLIMB)- Velocity | 003 Week 24 Change from 002 Baseline | 0.04 tasks/ second | Standard Deviation 0.09 |
| Dose Level Group 3 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Climb Test (TTCLIMB)- Velocity | 003 Week 24 | 0.34 tasks/ second | Standard Deviation 0.148 |
| Dose Level Group 3 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Climb Test (TTCLIMB)- Velocity | 002 Baseline | 0.29 tasks/ second | Standard Deviation 0.164 |
| Dose Level Group 4 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Climb Test (TTCLIMB)- Velocity | 003 Week 24 | 0.29 tasks/ second | Standard Deviation 0.097 |
| Dose Level Group 4 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Climb Test (TTCLIMB)- Velocity | 003 Week 24 Change from 002 Baseline | 0.05 tasks/ second | Standard Deviation 0.061 |
| Dose Level Group 4 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Climb Test (TTCLIMB)- Velocity | 003 Baseline | 0.25 tasks/ second | Standard Deviation 0.082 |
| Dose Level Group 4 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Climb Test (TTCLIMB)- Velocity | 003 Week 12 Change from 002 Baseline | 0.02 tasks/ second | Standard Deviation 0.051 |
| Dose Level Group 4 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Climb Test (TTCLIMB)- Velocity | 002 Baseline | 0.24 tasks/ second | Standard Deviation 0.086 |
| Dose Level Group 4 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Climb Test (TTCLIMB)- Velocity | 003 Week 12 | 0.26 tasks/ second | Standard Deviation 0.095 |
Secondary
Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Run/Walk 10 Meters Test (TTRW)- Velocity
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.
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)
Population: All subjects who receive at least one dose of vamorolone study medication in the extension study will be included in the Safety Population. The Safety Population is the primary analysis population for safety assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Level Group 1 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Run/Walk 10 Meters Test (TTRW)- Velocity | 002 Baseline | 1.60 meters/ second | Standard Deviation 0.312 |
| Dose Level Group 1 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Run/Walk 10 Meters Test (TTRW)- Velocity | 003 Baseline | 1.57 meters/ second | Standard Deviation 0.371 |
| Dose Level Group 1 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Run/Walk 10 Meters Test (TTRW)- Velocity | 003 Week 12 | 1.54 meters/ second | Standard Deviation 0.306 |
| Dose Level Group 1 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Run/Walk 10 Meters Test (TTRW)- Velocity | 003 Week 12 Change from 002 Baseline | -0.06 meters/ second | Standard Deviation 0.261 |
| Dose Level Group 1 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Run/Walk 10 Meters Test (TTRW)- Velocity | 003 Week 24 | 1.55 meters/ second | Standard Deviation 0.384 |
| Dose Level Group 1 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Run/Walk 10 Meters Test (TTRW)- Velocity | 003 Week 24 Change from 002 Baseline | -0.05 meters/ second | Standard Deviation 0.311 |
| Dose Level Group 2 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Run/Walk 10 Meters Test (TTRW)- Velocity | 003 Week 24 Change from 002 Baseline | 0.06 meters/ second | Standard Deviation 0.21 |
| Dose Level Group 2 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Run/Walk 10 Meters Test (TTRW)- Velocity | 003 Week 12 Change from 002 Baseline | 0.00 meters/ second | Standard Deviation 0.307 |
| Dose Level Group 2 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Run/Walk 10 Meters Test (TTRW)- Velocity | 002 Baseline | 1.77 meters/ second | Standard Deviation 0.367 |
| Dose Level Group 2 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Run/Walk 10 Meters Test (TTRW)- Velocity | 003 Week 12 | 1.77 meters/ second | Standard Deviation 0.55 |
| Dose Level Group 2 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Run/Walk 10 Meters Test (TTRW)- Velocity | 003 Baseline | 1.78 meters/ second | Standard Deviation 0.414 |
| Dose Level Group 2 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Run/Walk 10 Meters Test (TTRW)- Velocity | 003 Week 24 | 1.84 meters/ second | Standard Deviation 0.486 |
| Dose Level Group 3 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Run/Walk 10 Meters Test (TTRW)- Velocity | 003 Baseline | 1.86 meters/ second | Standard Deviation 0.418 |
| Dose Level Group 3 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Run/Walk 10 Meters Test (TTRW)- Velocity | 003 Week 12 | 1.97 meters/ second | Standard Deviation 0.503 |
| Dose Level Group 3 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Run/Walk 10 Meters Test (TTRW)- Velocity | 003 Week 12 Change from 002 Baseline | 0.13 meters/ second | Standard Deviation 0.316 |
| Dose Level Group 3 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Run/Walk 10 Meters Test (TTRW)- Velocity | 003 Week 24 Change from 002 Baseline | 0.06 meters/ second | Standard Deviation 0.21 |
| Dose Level Group 3 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Run/Walk 10 Meters Test (TTRW)- Velocity | 003 Week 24 | 1.90 meters/ second | Standard Deviation 0.321 |
| Dose Level Group 3 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Run/Walk 10 Meters Test (TTRW)- Velocity | 002 Baseline | 1.84 meters/ second | Standard Deviation 0.347 |
| Dose Level Group 4 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Run/Walk 10 Meters Test (TTRW)- Velocity | 003 Week 24 | 1.89 meters/ second | Standard Deviation 0.378 |
| Dose Level Group 4 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Run/Walk 10 Meters Test (TTRW)- Velocity | 003 Week 24 Change from 002 Baseline | 0.27 meters/ second | Standard Deviation 0.254 |
| Dose Level Group 4 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Run/Walk 10 Meters Test (TTRW)- Velocity | 003 Baseline | 1.72 meters/ second | Standard Deviation 0.295 |
| Dose Level Group 4 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Run/Walk 10 Meters Test (TTRW)- Velocity | 003 Week 12 Change from 002 Baseline | 0.26 meters/ second | Standard Deviation 0.297 |
| Dose Level Group 4 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Run/Walk 10 Meters Test (TTRW)- Velocity | 002 Baseline | 1.64 meters/ second | Standard Deviation 0.279 |
| Dose Level Group 4 | Muscle Strength, Mobility, and Functional Exercise Capacity as Measured by Time to Run/Walk 10 Meters Test (TTRW)- Velocity | 003 Week 12 | 1.88 meters/ second | Standard Deviation 0.341 |
Secondary
Muscle Strength, Mobility, and Functional Exercise Capacity vs. Historical Controls as Measured by 6-minute Walk Test (6MWT) Meters
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.
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)
Population: All subjects who receive at least one dose of vamorolone study medication in the extension study will be included in the Safety Population. The Safety Population is the primary analysis population for safety assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Level Group 1 | Muscle Strength, Mobility, and Functional Exercise Capacity vs. Historical Controls as Measured by 6-minute Walk Test (6MWT) Meters | 002 Baseline | 316.2 Meters | Standard Deviation 59.47 |
| Dose Level Group 1 | Muscle Strength, Mobility, and Functional Exercise Capacity vs. Historical Controls as Measured by 6-minute Walk Test (6MWT) Meters | 003 Week 12 | 312.9 Meters | Standard Deviation 60.93 |
| Dose Level Group 1 | Muscle Strength, Mobility, and Functional Exercise Capacity vs. Historical Controls as Measured by 6-minute Walk Test (6MWT) Meters | 003 Week 24 | 306.2 Meters | Standard Deviation 68.08 |
| Dose Level Group 1 | Muscle Strength, Mobility, and Functional Exercise Capacity vs. Historical Controls as Measured by 6-minute Walk Test (6MWT) Meters | 003 Week 12 Change from 002 Baseline | 6.0 Meters | Standard Deviation 28.81 |
| Dose Level Group 1 | Muscle Strength, Mobility, and Functional Exercise Capacity vs. Historical Controls as Measured by 6-minute Walk Test (6MWT) Meters | 003 Baseline | 294.3 Meters | Standard Deviation 60.62 |
| Dose Level Group 1 | Muscle Strength, Mobility, and Functional Exercise Capacity vs. Historical Controls as Measured by 6-minute Walk Test (6MWT) Meters | 003 Week 24 Change from 002 Baseline | -11.6 Meters | Standard Deviation 29.45 |
| Dose Level Group 2 | Muscle Strength, Mobility, and Functional Exercise Capacity vs. Historical Controls as Measured by 6-minute Walk Test (6MWT) Meters | 003 Week 12 Change from 002 Baseline | 20.8 Meters | Standard Deviation 38.09 |
| Dose Level Group 2 | Muscle Strength, Mobility, and Functional Exercise Capacity vs. Historical Controls as Measured by 6-minute Walk Test (6MWT) Meters | 002 Baseline | 331.5 Meters | Standard Deviation 52.76 |
| Dose Level Group 2 | Muscle Strength, Mobility, and Functional Exercise Capacity vs. Historical Controls as Measured by 6-minute Walk Test (6MWT) Meters | 003 Baseline | 332.2 Meters | Standard Deviation 56.83 |
| Dose Level Group 2 | Muscle Strength, Mobility, and Functional Exercise Capacity vs. Historical Controls as Measured by 6-minute Walk Test (6MWT) Meters | 003 Week 12 | 358.7 Meters | Standard Deviation 71.47 |
| Dose Level Group 2 | Muscle Strength, Mobility, and Functional Exercise Capacity vs. Historical Controls as Measured by 6-minute Walk Test (6MWT) Meters | 003 Week 24 | 350.4 Meters | Standard Deviation 64.23 |
| Dose Level Group 2 | Muscle Strength, Mobility, and Functional Exercise Capacity vs. Historical Controls as Measured by 6-minute Walk Test (6MWT) Meters | 003 Week 24 Change from 002 Baseline | 18.9 Meters | Standard Deviation 41.08 |
| Dose Level Group 3 | Muscle Strength, Mobility, and Functional Exercise Capacity vs. Historical Controls as Measured by 6-minute Walk Test (6MWT) Meters | 003 Baseline | 341.1 Meters | Standard Deviation 49.42 |
| Dose Level Group 3 | Muscle Strength, Mobility, and Functional Exercise Capacity vs. Historical Controls as Measured by 6-minute Walk Test (6MWT) Meters | 003 Week 12 Change from 002 Baseline | 39.8 Meters | Standard Deviation 35.61 |
| Dose Level Group 3 | Muscle Strength, Mobility, and Functional Exercise Capacity vs. Historical Controls as Measured by 6-minute Walk Test (6MWT) Meters | 003 Week 24 | 383.1 Meters | Standard Deviation 63.38 |
| Dose Level Group 3 | Muscle Strength, Mobility, and Functional Exercise Capacity vs. Historical Controls as Measured by 6-minute Walk Test (6MWT) Meters | 002 Baseline | 353.9 Meters | Standard Deviation 65.4 |
| Dose Level Group 3 | Muscle Strength, Mobility, and Functional Exercise Capacity vs. Historical Controls as Measured by 6-minute Walk Test (6MWT) Meters | 003 Week 24 Change from 002 Baseline | 29.2 Meters | Standard Deviation 35.91 |
| Dose Level Group 3 | Muscle Strength, Mobility, and Functional Exercise Capacity vs. Historical Controls as Measured by 6-minute Walk Test (6MWT) Meters | 003 Week 12 | 393.7 Meters | Standard Deviation 59.72 |
| Dose Level Group 4 | Muscle Strength, Mobility, and Functional Exercise Capacity vs. Historical Controls as Measured by 6-minute Walk Test (6MWT) Meters | 003 Week 24 | 372.6 Meters | Standard Deviation 69.12 |
| Dose Level Group 4 | Muscle Strength, Mobility, and Functional Exercise Capacity vs. Historical Controls as Measured by 6-minute Walk Test (6MWT) Meters | 003 Week 12 | 369.9 Meters | Standard Deviation 69.47 |
| Dose Level Group 4 | Muscle Strength, Mobility, and Functional Exercise Capacity vs. Historical Controls as Measured by 6-minute Walk Test (6MWT) Meters | 003 Week 12 Change from 002 Baseline | 27.6 Meters | Standard Deviation 42 |
| Dose Level Group 4 | Muscle Strength, Mobility, and Functional Exercise Capacity vs. Historical Controls as Measured by 6-minute Walk Test (6MWT) Meters | 002 Baseline | 336.8 Meters | Standard Deviation 63.18 |
| Dose Level Group 4 | Muscle Strength, Mobility, and Functional Exercise Capacity vs. Historical Controls as Measured by 6-minute Walk Test (6MWT) Meters | 003 Week 24 Change from 002 Baseline | 43.9 Meters | Standard Deviation 43.72 |
| Dose Level Group 4 | Muscle Strength, Mobility, and Functional Exercise Capacity vs. Historical Controls as Measured by 6-minute Walk Test (6MWT) Meters | 003 Baseline | 335.1 Meters | Standard Deviation 80.13 |
Secondary
Serum Pharmacodynamics Biomarkers Measured by Levels of ACTH
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.
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)
Population: All subjects who receive at least one dose of vamorolone study medication in the extension study will be included in the Safety Population. The Safety Population is the primary analysis population for safety assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of ACTH | 003 Baseline | 15.9 pg/mL | Standard Deviation 4.52 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of ACTH | 003 Week 16 Change from 002 Baseline | -6.2 pg/mL | Standard Deviation 6.34 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of ACTH | 003 Week 8 | 13.0 pg/mL | Standard Deviation 6.25 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of ACTH | 003 Week 16 | 12.2 pg/mL | Standard Deviation 4.93 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of ACTH | 003 Week 26-29 Change from 002 Baseline | -7.8 pg/mL | Standard Deviation 4.19 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of ACTH | 003 Week 26-29 | 9.5 pg/mL | Standard Deviation 7.26 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of ACTH | 002 Baseline | 18.3 pg/mL | Standard Deviation 2.96 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of ACTH | 003 Week 24 Change from 002 Baseline | 0.6 pg/mL | Standard Deviation 6.63 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of ACTH | 003 Week 24 | 19.8 pg/mL | Standard Deviation 6.32 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of ACTH | 003 Week 8 Change from 002 Baseline | -5.3 pg/mL | Standard Deviation 6.92 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of ACTH | 002 Baseline | 18.0 pg/mL | Standard Deviation 6.88 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of ACTH | 003 Week 16 | 9.0 pg/mL | Standard Deviation 5.86 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of ACTH | 003 Baseline | 18.6 pg/mL | Standard Deviation 4.56 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of ACTH | 003 Week 8 Change from 002 Baseline | -10.5 pg/mL | Standard Deviation 9.32 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of ACTH | 003 Week 8 | 7.1 pg/mL | Standard Deviation 5.84 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of ACTH | 003 Week 16 Change from 002 Baseline | -9.1 pg/mL | Standard Deviation 9.89 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of ACTH | 003 Week 24 | 14.0 pg/mL | Standard Deviation 3.88 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of ACTH | 003 Week 24 Change from 002 Baseline | -4.0 pg/mL | Standard Deviation 5.48 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of ACTH | 003 Week 16 Change from 002 Baseline | -12.0 pg/mL | Standard Deviation 15.42 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of ACTH | 003 Week 24 | 15.7 pg/mL | Standard Deviation 9.63 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of ACTH | 003 Week 8 Change from 002 Baseline | -13.3 pg/mL | Standard Deviation 7.33 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of ACTH | 002 Baseline | 21.1 pg/mL | Standard Deviation 6.13 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of ACTH | 003 Baseline | 18.2 pg/mL | Standard Deviation 5.29 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of ACTH | 003 Week 8 | 7.8 pg/mL | Standard Deviation 4.42 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of ACTH | 003 Week 24 Change from 002 Baseline | -5.4 pg/mL | Standard Deviation 11.09 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of ACTH | 003 Week 16 | 9.0 pg/mL | Standard Deviation 14.18 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of ACTH | 003 Baseline | 18.4 pg/mL | Standard Deviation 9.73 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of ACTH | 003 Week 16 Change from 002 Baseline | -12.2 pg/mL | Standard Deviation 8.16 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of ACTH | 003 Week 16 | 9.0 pg/mL | Standard Deviation 4.49 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of ACTH | 002 Baseline | 19.3 pg/mL | Standard Deviation 8.67 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of ACTH | 003 Week 24 Change from 002 Baseline | -6.3 pg/mL | Standard Deviation 7.78 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of ACTH | 003 Week 24 | 11.3 pg/mL | Standard Deviation 7.52 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of ACTH | 003 Week 8 | 6.5 pg/mL | Standard Deviation 5.23 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of ACTH | 003 Week 8 Change from 002 Baseline | -13.5 pg/mL | Standard Deviation 7.84 |
Secondary
Serum Pharmacodynamics Biomarkers Measured by Levels of CTX
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.
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)
Population: All subjects who receive at least one dose of vamorolone study medication in the extension study will be included in the Safety Population. The Safety Population is the primary analysis population for safety assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of CTX | 002 Baseline | 871.0 pg/mL | Standard Deviation 160.85 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of CTX | 003 Baseline | 915.9 pg/mL | Standard Deviation 263.13 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of CTX | 003 Week 8 | 897.1 pg/mL | Standard Deviation 365.45 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of CTX | 003 Week 8 Change from 002 Baseline | 26.1 pg/mL | Standard Deviation 368.76 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of CTX | 003 Week 16 | 885.4 pg/mL | Standard Deviation 261.53 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of CTX | 003 Week 16 Change from 002 Baseline | -2.6 pg/mL | Standard Deviation 304.5 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of CTX | 003 Week 24 | 1109.3 pg/mL | Standard Deviation 287.92 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of CTX | 003 Week 24 Change from 002 Baseline | 212.3 pg/mL | Standard Deviation 318.86 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of CTX | 003 Week 26-29 | 1059.3 pg/mL | Standard Deviation 536.26 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of CTX | 003 Week 26-29 Change from 002 Baseline | 569.5 pg/mL | Standard Deviation 28.99 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of CTX | 003 Baseline | 964.4 pg/mL | Standard Deviation 319.26 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of CTX | 003 Week 16 Change from 002 Baseline | -46.3 pg/mL | Standard Deviation 321.06 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of CTX | 003 Week 24 Change from 002 Baseline | 295.6 pg/mL | Standard Deviation 357.93 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of CTX | 003 Week 8 Change from 002 Baseline | -31.6 pg/mL | Standard Deviation 236.34 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of CTX | 003 Week 8 | 933.3 pg/mL | Standard Deviation 330.2 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of CTX | 003 Week 24 | 1235.6 pg/mL | Standard Deviation 295.79 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of CTX | 002 Baseline | 935.8 pg/mL | Standard Deviation 286.5 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of CTX | 003 Week 16 | 912.8 pg/mL | Standard Deviation 305.08 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of CTX | 003 Week 16 Change from 002 Baseline | 3.0 pg/mL | Standard Deviation 244.71 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of CTX | 003 Week 8 Change from 002 Baseline | -8.5 pg/mL | Standard Deviation 248.82 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of CTX | 003 Week 16 | 939.8 pg/mL | Standard Deviation 157.17 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of CTX | 003 Week 8 | 928.3 pg/mL | Standard Deviation 333.11 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of CTX | 003 Week 24 Change from 002 Baseline | 346.5 pg/mL | Standard Deviation 327.16 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of CTX | 002 Baseline | 936.8 pg/mL | Standard Deviation 256.25 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of CTX | 003 Baseline | 949.8 pg/mL | Standard Deviation 303.76 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of CTX | 003 Week 24 | 1248.7 pg/mL | Standard Deviation 308.9 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of CTX | 003 Baseline | 989.2 pg/mL | Standard Deviation 216.29 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of CTX | 002 Baseline | 889.3 pg/mL | Standard Deviation 186.68 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of CTX | 003 Week 8 Change from 002 Baseline | -59.6 pg/mL | Standard Deviation 259.08 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of CTX | 003 Week 16 | 953.7 pg/mL | Standard Deviation 199.53 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of CTX | 003 Week 24 | 1237.0 pg/mL | Standard Deviation 277.2 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of CTX | 003 Week 16 Change from 002 Baseline | 102.3 pg/mL | Standard Deviation 230.44 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of CTX | 003 Week 8 | 825.5 pg/mL | Standard Deviation 164.36 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of CTX | 003 Week 24 Change from 002 Baseline | 321.4 pg/mL | Standard Deviation 264.65 |
Secondary
Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Glucose
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.
Time frame: 002 Baseline, 003 Week 12, 003 Week 24
Population: All subjects who receive at least one dose of vamorolone study medication in the extension study will be included in the Safety Population. The Safety Population is the primary analysis population for safety assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Glucose | 003 Week 24 | 80.8 mg/dL | Standard Deviation 6.56 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Glucose | 003 Week 24 Change from 002 Baseline | -6.3 mg/dL | Standard Deviation 11.97 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Glucose | 003 Week 12 | 81.5 mg/dL | Standard Deviation 5.61 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Glucose | 003 Week 12 Change from 002 Baseline | -6.8 mg/dL | Standard Deviation 8.29 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Glucose | 002 Baseline | 87.5 mg/dL | Standard Deviation 9.44 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Glucose | 003 Week 12 Change from 002 Baseline | -7.6 mg/dL | Standard Deviation 19.22 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Glucose | 003 Week 24 | 80.8 mg/dL | Standard Deviation 4.08 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Glucose | 003 Week 12 | 81.7 mg/dL | Standard Deviation 4.35 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Glucose | 002 Baseline | 88.9 mg/dL | Standard Deviation 18.71 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Glucose | 003 Week 24 Change from 002 Baseline | -9.0 mg/dL | Standard Deviation 20.87 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Glucose | 003 Week 12 Change from 002 Baseline | -5.1 mg/dL | Standard Deviation 9.01 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Glucose | 002 Baseline | 89.3 mg/dL | Standard Deviation 7.91 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Glucose | 003 Week 12 | 84.3 mg/dL | Standard Deviation 8.13 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Glucose | 003 Week 24 | 81.3 mg/dL | Standard Deviation 7.94 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Glucose | 003 Week 24 Change from 002 Baseline | -8.1 mg/dL | Standard Deviation 10.28 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Glucose | 003 Week 24 Change from 002 Baseline | -7.8 mg/dL | Standard Deviation 9.44 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Glucose | 003 Week 24 | 84.6 mg/dL | Standard Deviation 6.53 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Glucose | 002 Baseline | 92.3 mg/dL | Standard Deviation 8.19 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Glucose | 003 Week 12 Change from 002 Baseline | -5.2 mg/dL | Standard Deviation 9.21 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Glucose | 003 Week 12 | 86.5 mg/dL | Standard Deviation 5.57 |
Secondary
Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Insulin
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.
Time frame: 002 Baseline, 003 Week 12, 003 Week 24
Population: All subjects who receive at least one dose of vamorolone study medication in the extension study will be included in the Safety Population. The Safety Population is the primary analysis population for safety assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Insulin | 003 Week 24 | 4.23 uIU/mL | Standard Deviation 2.56 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Insulin | 003 Week 12 | 4.17 uIU/mL | Standard Deviation 3.167 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Insulin | 003 Week 24 Change from 002 Baseline | -1.67 uIU/mL | Standard Deviation 4.478 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Insulin | 003 Week 12 Change from 002 Baseline | -1.13 uIU/mL | Standard Deviation 3.822 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Insulin | 002 Baseline | 5.54 uIU/mL | Standard Deviation 3.651 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Insulin | 003 Week 12 Change from 002 Baseline | -0.14 uIU/mL | Standard Deviation 1.756 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Insulin | 003 Week 24 | 3.12 uIU/mL | Standard Deviation 1.788 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Insulin | 003 Week 24 Change from 002 Baseline | 0.34 uIU/mL | Standard Deviation 2.898 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Insulin | 003 Week 12 | 2.97 uIU/mL | Standard Deviation 1.669 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Insulin | 002 Baseline | 3.09 uIU/mL | Standard Deviation 2.033 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Insulin | 003 Week 12 Change from 002 Baseline | 0.49 uIU/mL | Standard Deviation 2.592 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Insulin | 002 Baseline | 3.40 uIU/mL | Standard Deviation 1.548 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Insulin | 003 Week 12 | 3.89 uIU/mL | Standard Deviation 2.189 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Insulin | 003 Week 24 | 4.82 uIU/mL | Standard Deviation 3.393 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Insulin | 003 Week 24 Change from 002 Baseline | 1.36 uIU/mL | Standard Deviation 3.262 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Insulin | 003 Week 24 | 7.21 uIU/mL | Standard Deviation 2.374 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Insulin | 003 Week 12 | 6.97 uIU/mL | Standard Deviation 3.526 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Insulin | 002 Baseline | 3.96 uIU/mL | Standard Deviation 2.027 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Insulin | 003 Week 12 Change from 002 Baseline | 2.97 uIU/mL | Standard Deviation 2.277 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of Fasting Insulin | 003 Week 24 Change from 002 Baseline | 3.26 uIU/mL | Standard Deviation 2.862 |
Secondary
Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c
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.
Time frame: 002 Baseline, 003 Week 8, 003 Week 16, 003 Week 24, 003 Week 26-29
Population: All subjects who receive at least one dose of vamorolone study medication in the extension study will be included in the Safety Population. The Safety Population is the primary analysis population for safety assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c | 003 Week 8 % Change from 002 Baseline | 0.06 % change | Standard Deviation 2.47 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c | 003 Week 26-29 % Change from 002 Baseline | -1.25 % change | Standard Deviation 3.942 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c | 003 Week 16 % Change from 002 Baseline | 1.70 % change | Standard Deviation 3.989 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c | 003 Week 24 % Change from 002 Baseline | -1.89 % change | Standard Deviation 4.801 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c | 003 Week 8 % Change from 002 Baseline | 2.28 % change | Standard Deviation 3.008 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c | 003 Week 16 % Change from 002 Baseline | 2.72 % change | Standard Deviation 4.457 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c | 003 Week 24 % Change from 002 Baseline | 0.08 % change | Standard Deviation 3.629 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c | 003 Week 16 % Change from 002 Baseline | 1.30 % change | Standard Deviation 2.505 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c | 003 Week 8 % Change from 002 Baseline | 1.79 % change | Standard Deviation 3.864 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c | 003 Week 24 % Change from 002 Baseline | -1.27 % change | Standard Deviation 2.525 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c | 003 Week 24 % Change from 002 Baseline | -0.33 % change | Standard Deviation 2.895 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c | 003 Week 16 % Change from 002 Baseline | 1.03 % change | Standard Deviation 2.14 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c | 003 Week 8 % Change from 002 Baseline | 0.02 % change | Standard Deviation 1.927 |
Secondary
Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c
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.
Time frame: 002 Baseline, 003 Week 8, 003 Week 16, 003 Week 24, 003 Week 26-29
Population: All subjects who receive at least one dose of vamorolone study medication in the extension study will be included in the Safety Population. The Safety Population is the primary analysis population for safety assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c | 002 Baseline | 5.18 % of HbA1c | Standard Deviation 0.26 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c | 003 Week 8 | 5.18 % of HbA1c | Standard Deviation 0.226 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c | 003 Week 8 Change from 002 Baseline | 0.00 % of HbA1c | Standard Deviation 0.128 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c | 003 Week 16 | 5.26 % of HbA1c | Standard Deviation 0.239 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c | 003 Week 24 | 5.15 % of HbA1c | Standard Deviation 0.302 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c | 003 Week 26-29 Change from 002 Baseline | -0.07 % of HbA1c | Standard Deviation 0.208 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c | 003 Week 16 Change from 002 Baseline | 0.08 % of HbA1c | Standard Deviation 0.204 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c | 003 Week 24 Change from 002 Baseline | -0.10 % of HbA1c | Standard Deviation 0.22 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c | 003 Week 26-29 | 5.07 % of HbA1c | Standard Deviation 0.208 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c | 003 Week 8 Change from 002 Baseline | 0.12 % of HbA1c | Standard Deviation 0.153 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c | 003 Week 16 | 5.35 % of HbA1c | Standard Deviation 0.238 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c | 003 Week 16 Change from 002 Baseline | 0.14 % of HbA1c | Standard Deviation 0.225 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c | 003 Week 24 | 5.22 % of HbA1c | Standard Deviation 0.221 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c | 002 Baseline | 5.22 % of HbA1c | Standard Deviation 0.244 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c | 003 Week 24 Change from 002 Baseline | 0.00 % of HbA1c | Standard Deviation 0.186 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c | 003 Week 8 | 5.33 % of HbA1c | Standard Deviation 0.25 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c | 002 Baseline | 5.19 % of HbA1c | Standard Deviation 0.124 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c | 003 Week 8 Change from 002 Baseline | 0.09 % of HbA1c | Standard Deviation 0.198 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c | 003 Week 16 Change from 002 Baseline | 0.07 % of HbA1c | Standard Deviation 0.13 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c | 003 Week 24 | 5.13 % of HbA1c | Standard Deviation 0.16 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c | 003 Week 24 Change from 002 Baseline | -0.07 % of HbA1c | Standard Deviation 0.13 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c | 003 Week 16 | 5.26 % of HbA1c | Standard Deviation 0.156 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c | 003 Week 8 | 5.28 % of HbA1c | Standard Deviation 0.204 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c | 003 Week 16 | 5.31 % of HbA1c | Standard Deviation 0.27 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c | 003 Week 24 Change from 002 Baseline | -0.02 % of HbA1c | Standard Deviation 0.154 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c | 003 Week 24 | 5.24 % of HbA1c | Standard Deviation 0.254 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c | 003 Week 8 Change from 002 Baseline | 0.00 % of HbA1c | Standard Deviation 0.1 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c | 003 Week 16 Change from 002 Baseline | 0.05 % of HbA1c | Standard Deviation 0.113 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c | 002 Baseline | 5.23 % of HbA1c | Standard Deviation 0.231 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of HbA1c | 003 Week 8 | 5.25 % of HbA1c | Standard Deviation 0.216 |
Secondary
Serum Pharmacodynamics Biomarkers Measured by Levels of Osteocalcin
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.
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)
Population: All subjects who receive at least one dose of vamorolone study medication in the extension study will be included in the Safety Population. The Safety Population is the primary analysis population for safety assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of Osteocalcin | 002 Baseline | 37.94 ng/mL | Standard Deviation 11.622 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of Osteocalcin | 003 Baseline | 39.20 ng/mL | Standard Deviation 14.136 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of Osteocalcin | 003 Week 8 | 36.21 ng/mL | Standard Deviation 10.374 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of Osteocalcin | 003 Week 8 Change from 002 Baseline | -1.60 ng/mL | Standard Deviation 8.849 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of Osteocalcin | 003 Week 16 | 39.01 ng/mL | Standard Deviation 9.62 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of Osteocalcin | 003 Week 16 Change from 002 Baseline | 1.07 ng/mL | Standard Deviation 9.916 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of Osteocalcin | 003 Week 24 | 38.80 ng/mL | Standard Deviation 6.292 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of Osteocalcin | 003 Week 24 Change from 002 Baseline | -1.34 ng/mL | Standard Deviation 11.289 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of Osteocalcin | 003 Week 26-29 | 40.10 ng/mL | Standard Deviation 18.729 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of Osteocalcin | 003 Week 26-29 Change from 002 Baseline | -1.23 ng/mL | Standard Deviation 17.943 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of Osteocalcin | 003 Baseline | 41.84 ng/mL | Standard Deviation 8.552 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of Osteocalcin | 003 Week 16 Change from 002 Baseline | 6.57 ng/mL | Standard Deviation 6.709 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of Osteocalcin | 003 Week 24 Change from 002 Baseline | 15.75 ng/mL | Standard Deviation 10.211 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of Osteocalcin | 003 Week 8 Change from 002 Baseline | 6.13 ng/mL | Standard Deviation 10.44 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of Osteocalcin | 003 Week 8 | 41.78 ng/mL | Standard Deviation 13.856 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of Osteocalcin | 003 Week 24 | 51.41 ng/mL | Standard Deviation 11.265 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of Osteocalcin | 002 Baseline | 35.66 ng/mL | Standard Deviation 6.8 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of Osteocalcin | 003 Week 16 | 42.23 ng/mL | Standard Deviation 9.393 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of Osteocalcin | 003 Week 16 Change from 002 Baseline | 3.43 ng/mL | Standard Deviation 10.718 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of Osteocalcin | 003 Week 8 Change from 002 Baseline | 3.28 ng/mL | Standard Deviation 8.325 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of Osteocalcin | 003 Week 16 | 44.60 ng/mL | Standard Deviation 9.534 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of Osteocalcin | 003 Week 8 | 44.45 ng/mL | Standard Deviation 7.439 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of Osteocalcin | 003 Week 24 Change from 002 Baseline | 10.81 ng/mL | Standard Deviation 7.542 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of Osteocalcin | 002 Baseline | 41.17 ng/mL | Standard Deviation 5.617 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of Osteocalcin | 003 Baseline | 47.91 ng/mL | Standard Deviation 6.648 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of Osteocalcin | 003 Week 24 | 51.98 ng/mL | Standard Deviation 9.372 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of Osteocalcin | 003 Baseline | 42.81 ng/mL | Standard Deviation 10.851 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of Osteocalcin | 002 Baseline | 44.36 ng/mL | Standard Deviation 5.979 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of Osteocalcin | 003 Week 8 Change from 002 Baseline | -2.01 ng/mL | Standard Deviation 8.898 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of Osteocalcin | 003 Week 16 | 39.39 ng/mL | Standard Deviation 6.972 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of Osteocalcin | 003 Week 24 | 49.08 ng/mL | Standard Deviation 7.771 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of Osteocalcin | 003 Week 16 Change from 002 Baseline | -4.17 ng/mL | Standard Deviation 8.494 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of Osteocalcin | 003 Week 8 | 41.55 ng/mL | Standard Deviation 5.446 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of Osteocalcin | 003 Week 24 Change from 002 Baseline | 5.29 ng/mL | Standard Deviation 7.858 |
Secondary
Serum Pharmacodynamics Biomarkers Measured by Levels of P1NP
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.
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)
Population: All subjects who receive at least one dose of vamorolone study medication in the extension study will be included in the Safety Population. The Safety Population is the primary analysis population for safety assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of P1NP | 002 Baseline | 555.8 ng/mL | Standard Deviation 184.72 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of P1NP | 003 Baseline | 573.9 ng/mL | Standard Deviation 251.02 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of P1NP | 003 Week 8 | 511.6 ng/mL | Standard Deviation 190.94 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of P1NP | 003 Week 8 Change from 002 Baseline | -20.3 ng/mL | Standard Deviation 120.32 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of P1NP | 003 Week 16 | 481.9 ng/mL | Standard Deviation 159.93 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of P1NP | 003 Week 16 Change from 002 Baseline | -73.8 ng/mL | Standard Deviation 109.31 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of P1NP | 003 Week 24 | 457.1 ng/mL | Standard Deviation 129.21 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of P1NP | 003 Week 24 Change from 002 Baseline | -30.8 ng/mL | Standard Deviation 113.64 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of P1NP | 003 Week 26-29 | 619.0 ng/mL | Standard Deviation 379.07 |
| Dose Level Group 1 | Serum Pharmacodynamics Biomarkers Measured by Levels of P1NP | 003 Week 26-29 Change from 002 Baseline | -152.0 ng/mL | Standard Deviation 331.46 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of P1NP | 003 Baseline | 489.3 ng/mL | Standard Deviation 121.66 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of P1NP | 003 Week 16 Change from 002 Baseline | -42.4 ng/mL | Standard Deviation 109.07 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of P1NP | 003 Week 24 Change from 002 Baseline | 2.1 ng/mL | Standard Deviation 165.16 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of P1NP | 003 Week 8 Change from 002 Baseline | -22.9 ng/mL | Standard Deviation 128.79 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of P1NP | 003 Week 8 | 459.8 ng/mL | Standard Deviation 101.93 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of P1NP | 003 Week 24 | 471.1 ng/mL | Standard Deviation 121.1 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of P1NP | 002 Baseline | 480.7 ng/mL | Standard Deviation 118.2 |
| Dose Level Group 2 | Serum Pharmacodynamics Biomarkers Measured by Levels of P1NP | 003 Week 16 | 431.8 ng/mL | Standard Deviation 81.25 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of P1NP | 003 Week 16 Change from 002 Baseline | -52.5 ng/mL | Standard Deviation 104.05 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of P1NP | 003 Week 8 Change from 002 Baseline | -23.0 ng/mL | Standard Deviation 96.84 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of P1NP | 003 Week 16 | 455.7 ng/mL | Standard Deviation 99.5 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of P1NP | 003 Week 8 | 485.2 ng/mL | Standard Deviation 105.12 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of P1NP | 003 Week 24 Change from 002 Baseline | 57.3 ng/mL | Standard Deviation 150.36 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of P1NP | 002 Baseline | 508.2 ng/mL | Standard Deviation 94.36 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of P1NP | 003 Baseline | 492.0 ng/mL | Standard Deviation 81.92 |
| Dose Level Group 3 | Serum Pharmacodynamics Biomarkers Measured by Levels of P1NP | 003 Week 24 | 565.5 ng/mL | Standard Deviation 158.89 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of P1NP | 003 Baseline | 566.3 ng/mL | Standard Deviation 149.32 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of P1NP | 002 Baseline | 511.5 ng/mL | Standard Deviation 106.5 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of P1NP | 003 Week 8 Change from 002 Baseline | -105.6 ng/mL | Standard Deviation 121.07 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of P1NP | 003 Week 16 | 488.5 ng/mL | Standard Deviation 130.11 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of P1NP | 003 Week 24 | 526.2 ng/mL | Standard Deviation 130.18 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of P1NP | 003 Week 16 Change from 002 Baseline | -19.8 ng/mL | Standard Deviation 130.12 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of P1NP | 003 Week 8 | 402.7 ng/mL | Standard Deviation 70.46 |
| Dose Level Group 4 | Serum Pharmacodynamics Biomarkers Measured by Levels of P1NP | 003 Week 24 Change from 002 Baseline | 8.7 ng/mL | Standard Deviation 88.95 |