Trial Outcomes & Findings for A Futility Trial of Sirolimus in Multiple System Atrophy (NCT NCT03589976)
NCT ID: NCT03589976
Last Updated: 2021-12-07
Results Overview
UMSARS is a validated, disease-specific scale representing the diverse signs and symptoms in MSA. USMARS has an Activities of Daily Living score (UMSARS-1, 12 questions) that evaluates motor including autonomic activities and the Motor Examination score (UMSARS-2, 14 questions). UMSARS-3 measures supine/standing BP and UMSARS-4 is a disability scale. The total range of score is 1-109; Higher scores on the UMSARS scales mean poorer health.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
47 participants
Primary outcome timeframe
Baseline, 48 Weeks
Results posted on
2021-12-07
Participant Flow
Participant milestones
| Measure |
Sirolimus
2 mg/day (one 2-mg tablet/day). The dose of sirolimus will be adjusted throughout the trial based on sirolimus plasma levels and the presence of drug-related adverse events. The maximum dose of sirolimus will be6 mg/day (three 2-mg tablets/day).
Sirolimus 2 MG: Dose will be adjusted throughout this trial based on sirolimus plasma levels and the presence of drug-related adverse events. The maximum dose will be 6mg/day.
|
Placebo
Patients receiving placebo will undergo analog sham level measurements and the number of tablets will be also adjusted to maintain the blinding of the trial.
Placebo: Patients receiving placebo will undergo analog sham level measurements and the number of tablets will be also adjusted to maintain the blinding of the trial.
|
|---|---|---|
|
Overall Study
STARTED
|
35
|
12
|
|
Overall Study
COMPLETED
|
16
|
6
|
|
Overall Study
NOT COMPLETED
|
19
|
6
|
Reasons for withdrawal
| Measure |
Sirolimus
2 mg/day (one 2-mg tablet/day). The dose of sirolimus will be adjusted throughout the trial based on sirolimus plasma levels and the presence of drug-related adverse events. The maximum dose of sirolimus will be6 mg/day (three 2-mg tablets/day).
Sirolimus 2 MG: Dose will be adjusted throughout this trial based on sirolimus plasma levels and the presence of drug-related adverse events. The maximum dose will be 6mg/day.
|
Placebo
Patients receiving placebo will undergo analog sham level measurements and the number of tablets will be also adjusted to maintain the blinding of the trial.
Placebo: Patients receiving placebo will undergo analog sham level measurements and the number of tablets will be also adjusted to maintain the blinding of the trial.
|
|---|---|---|
|
Overall Study
Death
|
5
|
1
|
|
Overall Study
Adverse Event
|
5
|
1
|
|
Overall Study
Withdrawal by Subject
|
4
|
1
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
|
Overall Study
Other
|
4
|
3
|
Baseline Characteristics
A Futility Trial of Sirolimus in Multiple System Atrophy
Baseline characteristics by cohort
| Measure |
Sirolimus
n=35 Participants
2 mg/day (one 2-mg tablet/day). The dose of sirolimus will be adjusted throughout the trial based on sirolimus plasma levels and the presence of drug-related adverse events. The maximum dose of sirolimus will be6 mg/day (three 2-mg tablets/day).
Sirolimus 2 MG: Dose will be adjusted throughout this trial based on sirolimus plasma levels and the presence of drug-related adverse events. The maximum dose will be 6mg/day.
|
Placebo
n=12 Participants
Patients receiving placebo will undergo analog sham level measurements and the number of tablets will be also adjusted to maintain the blinding of the trial.
Placebo: Patients receiving placebo will undergo analog sham level measurements and the number of tablets will be also adjusted to maintain the blinding of the trial.
|
Total
n=47 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
59 years
n=99 Participants
|
58 years
n=107 Participants
|
58 years
n=206 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
20 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
21 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
27 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
33 Participants
n=99 Participants
|
11 Participants
n=107 Participants
|
44 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
3 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
30 Participants
n=99 Participants
|
12 Participants
n=107 Participants
|
42 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
35 participants
n=99 Participants
|
12 participants
n=107 Participants
|
47 participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Baseline, 48 WeeksUMSARS is a validated, disease-specific scale representing the diverse signs and symptoms in MSA. USMARS has an Activities of Daily Living score (UMSARS-1, 12 questions) that evaluates motor including autonomic activities and the Motor Examination score (UMSARS-2, 14 questions). UMSARS-3 measures supine/standing BP and UMSARS-4 is a disability scale. The total range of score is 1-109; Higher scores on the UMSARS scales mean poorer health.
Outcome measures
| Measure |
Sirolimus
n=25 Participants
2 mg/day (one 2-mg tablet/day). The dose of sirolimus will be adjusted throughout the trial based on sirolimus plasma levels and the presence of drug-related adverse events. The maximum dose of sirolimus will be6 mg/day (three 2-mg tablets/day).
Sirolimus 2 MG: Dose will be adjusted throughout this trial based on sirolimus plasma levels and the presence of drug-related adverse events. The maximum dose will be 6mg/day.
|
Placebo
n=9 Participants
Patients receiving placebo will undergo analog sham level measurements and the number of tablets will be also adjusted to maintain the blinding of the trial.
Placebo: Patients receiving placebo will undergo analog sham level measurements and the number of tablets will be also adjusted to maintain the blinding of the trial.
|
|---|---|---|
|
Change From Baseline to 48 Weeks in United Multiple System Atrophy Rating Score (UMSARS) Total Score
|
13.92 score on a scale
Standard Deviation 8.32
|
11.3 score on a scale
Standard Deviation 8
|
SECONDARY outcome
Timeframe: Baseline, 48 WeeksThe Activities of Daily Living score (UMSARS-1, 12 questions) evaluates impact of symptoms, including autonomic, on activities of daily living. 12 functional situations are rated between 0-4. The total range of score is 0-48; the higher the score, the more problems conducting activities of daily living.
Outcome measures
| Measure |
Sirolimus
n=25 Participants
2 mg/day (one 2-mg tablet/day). The dose of sirolimus will be adjusted throughout the trial based on sirolimus plasma levels and the presence of drug-related adverse events. The maximum dose of sirolimus will be6 mg/day (three 2-mg tablets/day).
Sirolimus 2 MG: Dose will be adjusted throughout this trial based on sirolimus plasma levels and the presence of drug-related adverse events. The maximum dose will be 6mg/day.
|
Placebo
n=9 Participants
Patients receiving placebo will undergo analog sham level measurements and the number of tablets will be also adjusted to maintain the blinding of the trial.
Placebo: Patients receiving placebo will undergo analog sham level measurements and the number of tablets will be also adjusted to maintain the blinding of the trial.
|
|---|---|---|
|
Change From Baseline to 48 Weeks in UMSARS-1
|
5.65 score on a scale
Standard Deviation 5.91
|
5.33 score on a scale
Standard Deviation 3.81
|
Adverse Events
Sirolimus
Serious events: 9 serious events
Other events: 31 other events
Deaths: 5 deaths
Placebo
Serious events: 2 serious events
Other events: 9 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Sirolimus
n=35 participants at risk
2 mg/day (one 2-mg tablet/day). The dose of sirolimus will be adjusted throughout the trial based on sirolimus plasma levels and the presence of drug-related adverse events. The maximum dose of sirolimus will be6 mg/day (three 2-mg tablets/day).
Sirolimus 2 MG: Dose will be adjusted throughout this trial based on sirolimus plasma levels and the presence of drug-related adverse events. The maximum dose will be 6mg/day.
|
Placebo
n=12 participants at risk
Patients receiving placebo will undergo analog sham level measurements and the number of tablets will be also adjusted to maintain the blinding of the trial.
Placebo: Patients receiving placebo will undergo analog sham level measurements and the number of tablets will be also adjusted to maintain the blinding of the trial.
|
|---|---|---|
|
General disorders
Death
|
14.3%
5/35 • month 12 after initiation of study drug) (+ 15 days)
|
8.3%
1/12 • month 12 after initiation of study drug) (+ 15 days)
|
|
General disorders
Other
|
11.4%
4/35 • month 12 after initiation of study drug) (+ 15 days)
|
8.3%
1/12 • month 12 after initiation of study drug) (+ 15 days)
|
Other adverse events
| Measure |
Sirolimus
n=35 participants at risk
2 mg/day (one 2-mg tablet/day). The dose of sirolimus will be adjusted throughout the trial based on sirolimus plasma levels and the presence of drug-related adverse events. The maximum dose of sirolimus will be6 mg/day (three 2-mg tablets/day).
Sirolimus 2 MG: Dose will be adjusted throughout this trial based on sirolimus plasma levels and the presence of drug-related adverse events. The maximum dose will be 6mg/day.
|
Placebo
n=12 participants at risk
Patients receiving placebo will undergo analog sham level measurements and the number of tablets will be also adjusted to maintain the blinding of the trial.
Placebo: Patients receiving placebo will undergo analog sham level measurements and the number of tablets will be also adjusted to maintain the blinding of the trial.
|
|---|---|---|
|
Infections and infestations
Infections
|
60.0%
21/35 • month 12 after initiation of study drug) (+ 15 days)
|
33.3%
4/12 • month 12 after initiation of study drug) (+ 15 days)
|
|
Skin and subcutaneous tissue disorders
Aphthae, gingivitis, and oral herpes-like vesicles
|
42.9%
15/35 • month 12 after initiation of study drug) (+ 15 days)
|
16.7%
2/12 • month 12 after initiation of study drug) (+ 15 days)
|
|
Gastrointestinal disorders
Diarrhea
|
45.7%
16/35 • month 12 after initiation of study drug) (+ 15 days)
|
16.7%
2/12 • month 12 after initiation of study drug) (+ 15 days)
|
|
Vascular disorders
Edema in Lower Limbs
|
48.6%
17/35 • month 12 after initiation of study drug) (+ 15 days)
|
8.3%
1/12 • month 12 after initiation of study drug) (+ 15 days)
|
|
Skin and subcutaneous tissue disorders
Acne, Petechiae, Rash
|
37.1%
13/35 • month 12 after initiation of study drug) (+ 15 days)
|
16.7%
2/12 • month 12 after initiation of study drug) (+ 15 days)
|
|
Nervous system disorders
Fall
|
17.1%
6/35 • month 12 after initiation of study drug) (+ 15 days)
|
33.3%
4/12 • month 12 after initiation of study drug) (+ 15 days)
|
|
Gastrointestinal disorders
Nausea
|
8.6%
3/35 • month 12 after initiation of study drug) (+ 15 days)
|
8.3%
1/12 • month 12 after initiation of study drug) (+ 15 days)
|
|
Nervous system disorders
Worsening of Movement Disorder
|
11.4%
4/35 • month 12 after initiation of study drug) (+ 15 days)
|
8.3%
1/12 • month 12 after initiation of study drug) (+ 15 days)
|
|
General disorders
Fatigue
|
2.9%
1/35 • month 12 after initiation of study drug) (+ 15 days)
|
58.3%
7/12 • month 12 after initiation of study drug) (+ 15 days)
|
|
General disorders
Other
|
71.4%
25/35 • month 12 after initiation of study drug) (+ 15 days)
|
33.3%
4/12 • month 12 after initiation of study drug) (+ 15 days)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place