Trial Outcomes & Findings for Efficacy and Safety on SOM3355 in Huntington's Disease Chorea (NCT NCT05475483)
NCT ID: NCT05475483
Last Updated: 2025-08-28
Results Overview
Pre-defined analysis of the primary efficacy endpoint (change in TMC score from baseline to the end of maintenance dose) performed with the 122 subjects of the mITT not taking neuroleptics during the trial. The TMC is part of the motor assessment of the Unified Huntington's Disease Rating Scale (UHDRS) and measures chorea in 7 different body parts, including the face, oral-buccal-lingual region, trunk, and each limb independently. The TMC score is the sum of the individual scores, ranging from 0 to 28. A decrease in TMC scores indicates improvement in chorea symptoms.
COMPLETED
PHASE2
139 participants
From baseline to end of maintenance dose (10 weeks of treatment).
2025-08-28
Participant Flow
A total of 139 patients with Huntington's disease were randomized and treated between August 2022 and April 2024 at 23 sites in 7 European countries.
Participant milestones
| Measure |
Placebo
Placebo capsules were administered twice daily (BID) for at least 9 weeks at maintenance dose.
Placebo capsules: Treatment was blind for the whole duration of the study.
|
SOM3355 400 mg/Day
SOM3355 200 mg capsules were administered twice daily (BID) for at least 9 weeks at maintenance dose.
SOM3355 200 mg capsules: Treatment was blind for the whole duration of the study.
|
SOM3355 600 mg/Day
SOM3355 300 mg capsules were administered twice daily (BID) for at least 8 weeks at maintenance dose.
SOM3355 300 mg capsules: Treatment was blind for the whole duration of the study.
|
|---|---|---|---|
|
Overall Study
STARTED
|
48
|
41
|
50
|
|
Overall Study
COMPLETED
|
41
|
36
|
41
|
|
Overall Study
NOT COMPLETED
|
7
|
5
|
9
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Efficacy and Safety on SOM3355 in Huntington's Disease Chorea
Baseline characteristics by cohort
| Measure |
Placebo
n=48 Participants
Placebo capsules were administered twice daily (BID) for at least 9 weeks at maintenance dose.
Placebo capsules: Treatment was blind for the whole duration of the study.
|
SOM3355 400 mg/Day
n=41 Participants
SOM3355 200 mg capsules were administered twice daily (BID) for at least 9 weeks at maintenance dose.
SOM3355 200 mg capsules: Treatment was blind for the whole duration of the study.
|
SOM3355 600 mg/Day
n=50 Participants
SOM3355 300 mg capsules were administered twice daily (BID) for at least 8 weeks at maintenance dose.
SOM3355 300 mg capsules: Treatment was blind for the whole duration of the study.
|
Total
n=139 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
43 Participants
n=5 Participants
|
32 Participants
n=7 Participants
|
45 Participants
n=5 Participants
|
120 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
5 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
19 Participants
n=4 Participants
|
|
Age, Continuous
|
51.65 years
STANDARD_DEVIATION 10.46 • n=5 Participants
|
52.51 years
STANDARD_DEVIATION 12.39 • n=7 Participants
|
51.34 years
STANDARD_DEVIATION 12.12 • n=5 Participants
|
51.79 years
STANDARD_DEVIATION 11.58 • n=4 Participants
|
|
Sex: Female, Male
Female
|
28 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
66 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
29 Participants
n=5 Participants
|
73 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Ethnic Origin · White
|
48 Participants
n=5 Participants
|
39 Participants
n=7 Participants
|
48 Participants
n=5 Participants
|
135 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Ethnic Origin · African (North)
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Ethnic Origin · Latino
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Ethnic Origin · Other (in France)
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Region of Enrollment
Poland
|
8 participants
n=5 Participants
|
9 participants
n=7 Participants
|
9 participants
n=5 Participants
|
26 participants
n=4 Participants
|
|
Region of Enrollment
Italy
|
5 participants
n=5 Participants
|
6 participants
n=7 Participants
|
8 participants
n=5 Participants
|
19 participants
n=4 Participants
|
|
Region of Enrollment
United Kingdom
|
7 participants
n=5 Participants
|
4 participants
n=7 Participants
|
7 participants
n=5 Participants
|
18 participants
n=4 Participants
|
|
Region of Enrollment
France
|
7 participants
n=5 Participants
|
2 participants
n=7 Participants
|
6 participants
n=5 Participants
|
15 participants
n=4 Participants
|
|
Region of Enrollment
Switzerland
|
2 participants
n=5 Participants
|
1 participants
n=7 Participants
|
2 participants
n=5 Participants
|
5 participants
n=4 Participants
|
|
Region of Enrollment
Germany
|
7 participants
n=5 Participants
|
7 participants
n=7 Participants
|
7 participants
n=5 Participants
|
21 participants
n=4 Participants
|
|
Region of Enrollment
Spain
|
12 participants
n=5 Participants
|
12 participants
n=7 Participants
|
11 participants
n=5 Participants
|
35 participants
n=4 Participants
|
|
Use of Neuroleptics
Yes
|
6 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
17 Participants
n=4 Participants
|
|
Use of Neuroleptics
No
|
42 Participants
n=5 Participants
|
36 Participants
n=7 Participants
|
44 Participants
n=5 Participants
|
122 Participants
n=4 Participants
|
|
Total Maximal Chorea (TMC) score
|
12.80 units on a scale
STANDARD_DEVIATION 2.58 • n=5 Participants
|
12.74 units on a scale
STANDARD_DEVIATION 2.93 • n=7 Participants
|
13.23 units on a scale
STANDARD_DEVIATION 2.84 • n=5 Participants
|
12.94 units on a scale
STANDARD_DEVIATION 2.77 • n=4 Participants
|
PRIMARY outcome
Timeframe: From baseline to end of maintenance dose (10 weeks of treatment).Population: 122 subjects of the mITT not taking neuroleptics during the trial. The modified Intention-to-Treat (mITT) population comprises all patients randomized to a treatment arm who received at least one dose of study drug and had at least one post-baseline assessment of the TMC score (N=139).
Pre-defined analysis of the primary efficacy endpoint (change in TMC score from baseline to the end of maintenance dose) performed with the 122 subjects of the mITT not taking neuroleptics during the trial. The TMC is part of the motor assessment of the Unified Huntington's Disease Rating Scale (UHDRS) and measures chorea in 7 different body parts, including the face, oral-buccal-lingual region, trunk, and each limb independently. The TMC score is the sum of the individual scores, ranging from 0 to 28. A decrease in TMC scores indicates improvement in chorea symptoms.
Outcome measures
| Measure |
Placebo
n=42 Participants
Placebo capsules were administered twice daily (BID) for at least 9 weeks at maintenance dose.
Placebo capsules: Treatment was blind for the whole duration of the study.
|
SOM3355 400 mg/Day
n=36 Participants
SOM3355 200 mg capsules were administered twice daily (BID) for at least 9 weeks at maintenance dose.
SOM3355 200 mg capsules: Treatment was blind for the whole duration of the study.
|
SOM3355 600 mg/Day
n=44 Participants
SOM3355 300 mg capsules were administered twice daily (BID) for at least 8 weeks at maintenance dose.
SOM3355 300 mg capsules: Treatment was blind for the whole duration of the study.
|
|---|---|---|---|
|
Change in Total Maximal Chorea (TMC) Score of the UHDRS® for Subjects Not Taking Neuroleptics During the Trial (mITT - N=122)
|
-2.19 units on a scale
Interval -3.07 to -1.32
|
-2.42 units on a scale
Interval -3.32 to -1.51
|
-3.46 units on a scale
Interval -4.35 to -2.58
|
SECONDARY outcome
Timeframe: From baseline to end of maintenance dose (10 weeks of treatment).Population: Modified Intention-to-Treat (mITT) population included all patients randomized to a treatment arm, who received at least one dose of study drug and had at least one post-baseline assessment of the TMC score.
The key secondary endpoint was the Clinical Global Impression of Change (CGI-C) at Visit 5 (week 10). The key secondary efficacy analysis was conducted on the mITT Population, including 139 subjects. Subjects with a score of 1 (Very much improved), 2 (Much improved), or 3 (Minimally improved) were defined as "Improved", and patients with a score of 4 (No change), 5 (Worse), 6 (Much worse), and 7 (Very much worse) were defined as "Not Improved".
Outcome measures
| Measure |
Placebo
n=41 Participants
Placebo capsules were administered twice daily (BID) for at least 9 weeks at maintenance dose.
Placebo capsules: Treatment was blind for the whole duration of the study.
|
SOM3355 400 mg/Day
n=37 Participants
SOM3355 200 mg capsules were administered twice daily (BID) for at least 9 weeks at maintenance dose.
SOM3355 200 mg capsules: Treatment was blind for the whole duration of the study.
|
SOM3355 600 mg/Day
n=41 Participants
SOM3355 300 mg capsules were administered twice daily (BID) for at least 8 weeks at maintenance dose.
SOM3355 300 mg capsules: Treatment was blind for the whole duration of the study.
|
|---|---|---|---|
|
Change in the Clinical Global Impression (CGI) (mITT - N=139)
Improved
|
15 Participants
|
26 Participants
|
23 Participants
|
|
Change in the Clinical Global Impression (CGI) (mITT - N=139)
Not Improved
|
26 Participants
|
11 Participants
|
18 Participants
|
SECONDARY outcome
Timeframe: From baseline to end of maintenance dose (10 weeks of treatment).Population: Modified Intention-to-Treat (mITT) population included all patients randomized to a treatment arm, who received at least one dose of study drug and had at least one post-baseline assessment of the TMC score.
Another relevant secondary endpoint was the Patient Global Impression of Change (PGI-C) at Visit 5 (week 10). The efficacy analysis was conducted on the mITT Population, including 139 subjects. Subjects with a score of 1 (Very much improved), 2 (Much improved), or 3 (Minimally improved) were defined as "Improved", and patients with a score of 4 (No change), 5 (Worse), 6 (Much worse), and 7 (Very much worse) were defined as "Not Improved".
Outcome measures
| Measure |
Placebo
n=41 Participants
Placebo capsules were administered twice daily (BID) for at least 9 weeks at maintenance dose.
Placebo capsules: Treatment was blind for the whole duration of the study.
|
SOM3355 400 mg/Day
n=37 Participants
SOM3355 200 mg capsules were administered twice daily (BID) for at least 9 weeks at maintenance dose.
SOM3355 200 mg capsules: Treatment was blind for the whole duration of the study.
|
SOM3355 600 mg/Day
n=40 Participants
SOM3355 300 mg capsules were administered twice daily (BID) for at least 8 weeks at maintenance dose.
SOM3355 300 mg capsules: Treatment was blind for the whole duration of the study.
|
|---|---|---|---|
|
Change in the Patient Global Impression (PGI) (mITT - N=139)
Improved
|
20 Participants
|
25 Participants
|
26 Participants
|
|
Change in the Patient Global Impression (PGI) (mITT - N=139)
Not Improved
|
21 Participants
|
12 Participants
|
14 Participants
|
POST_HOC outcome
Timeframe: From baseline to end of maintenance dose (10 weeks of treatment).Population: 57 subjects of the mITT not taking neuroleptics during the trial and with a mean baseline TMC score \>12.
Post-hoc analysis of the primary efficacy endpoint (change in TMC score from baseline to the end of maintenance dose) was performed in 57 subjects of the mITT not taking neuroleptics during the trial and with a mean baseline TMC score \>12. The TMC is part of the motor assessment of the Unified Huntington's Disease Rating Scale (UHDRS) and measures chorea in 7 different body parts, including the face, oral-buccal-lingual region, trunk, and each limb independently. The TMC score is the sum of the individual scores, ranging from 0 to 28. A decrease in TMC scores indicates improvement in chorea symptoms.
Outcome measures
| Measure |
Placebo
n=21 Participants
Placebo capsules were administered twice daily (BID) for at least 9 weeks at maintenance dose.
Placebo capsules: Treatment was blind for the whole duration of the study.
|
SOM3355 400 mg/Day
n=14 Participants
SOM3355 200 mg capsules were administered twice daily (BID) for at least 9 weeks at maintenance dose.
SOM3355 200 mg capsules: Treatment was blind for the whole duration of the study.
|
SOM3355 600 mg/Day
n=22 Participants
SOM3355 300 mg capsules were administered twice daily (BID) for at least 8 weeks at maintenance dose.
SOM3355 300 mg capsules: Treatment was blind for the whole duration of the study.
|
|---|---|---|---|
|
Change in Total Maximal Chorea (TMC) Score for Subjects Not Taking Neuroleptics and With Mean Baseline TMC Score >12 (mITT - N=57)
|
-2.43 units on a scale
Interval -3.57 to -1.28
|
-2.76 units on a scale
Interval -4.2 to -1.32
|
-4.21 units on a scale
Interval -5.36 to -3.06
|
Adverse Events
Placebo
SOM3355 400 mg/Day
SOM3355 600 mg/Day
Serious adverse events
| Measure |
Placebo
n=48 participants at risk
Placebo capsules were administered twice daily (BID) for at least 9 weeks at maintenance dose.
Placebo capsules: Treatment was blind for the whole duration of the study.
|
SOM3355 400 mg/Day
n=41 participants at risk
SOM3355 200 mg capsules were administered twice daily (BID) for at least 9 weeks at maintenance dose.
SOM3355 200 mg capsules: Treatment was blind for the whole duration of the study.
|
SOM3355 600 mg/Day
n=50 participants at risk
SOM3355 300 mg capsules were administered twice daily (BID) for at least 8 weeks at maintenance dose.
SOM3355 300 mg capsules: Treatment was blind for the whole duration of the study.
|
|---|---|---|---|
|
Nervous system disorders
Syncope (overdose)
|
0.00%
0/48 • From Baseline (visit 1) until End of Study visit (up to 13 weeks of treatment).
|
0.00%
0/41 • From Baseline (visit 1) until End of Study visit (up to 13 weeks of treatment).
|
2.0%
1/50 • Number of events 1 • From Baseline (visit 1) until End of Study visit (up to 13 weeks of treatment).
|
|
Psychiatric disorders
Suicidal ideation
|
2.1%
1/48 • Number of events 1 • From Baseline (visit 1) until End of Study visit (up to 13 weeks of treatment).
|
0.00%
0/41 • From Baseline (visit 1) until End of Study visit (up to 13 weeks of treatment).
|
0.00%
0/50 • From Baseline (visit 1) until End of Study visit (up to 13 weeks of treatment).
|
|
Infections and infestations
Pneumonia pneumococcal
|
0.00%
0/48 • From Baseline (visit 1) until End of Study visit (up to 13 weeks of treatment).
|
2.4%
1/41 • Number of events 1 • From Baseline (visit 1) until End of Study visit (up to 13 weeks of treatment).
|
0.00%
0/50 • From Baseline (visit 1) until End of Study visit (up to 13 weeks of treatment).
|
Other adverse events
| Measure |
Placebo
n=48 participants at risk
Placebo capsules were administered twice daily (BID) for at least 9 weeks at maintenance dose.
Placebo capsules: Treatment was blind for the whole duration of the study.
|
SOM3355 400 mg/Day
n=41 participants at risk
SOM3355 200 mg capsules were administered twice daily (BID) for at least 9 weeks at maintenance dose.
SOM3355 200 mg capsules: Treatment was blind for the whole duration of the study.
|
SOM3355 600 mg/Day
n=50 participants at risk
SOM3355 300 mg capsules were administered twice daily (BID) for at least 8 weeks at maintenance dose.
SOM3355 300 mg capsules: Treatment was blind for the whole duration of the study.
|
|---|---|---|---|
|
Injury, poisoning and procedural complications
Fall
|
4.2%
2/48 • Number of events 5 • From Baseline (visit 1) until End of Study visit (up to 13 weeks of treatment).
|
7.3%
3/41 • Number of events 6 • From Baseline (visit 1) until End of Study visit (up to 13 weeks of treatment).
|
8.0%
4/50 • Number of events 7 • From Baseline (visit 1) until End of Study visit (up to 13 weeks of treatment).
|
|
Vascular disorders
Bradycardia
|
0.00%
0/48 • From Baseline (visit 1) until End of Study visit (up to 13 weeks of treatment).
|
4.9%
2/41 • Number of events 2 • From Baseline (visit 1) until End of Study visit (up to 13 weeks of treatment).
|
12.0%
6/50 • Number of events 7 • From Baseline (visit 1) until End of Study visit (up to 13 weeks of treatment).
|
|
Nervous system disorders
Somnolence
|
6.2%
3/48 • Number of events 3 • From Baseline (visit 1) until End of Study visit (up to 13 weeks of treatment).
|
2.4%
1/41 • Number of events 1 • From Baseline (visit 1) until End of Study visit (up to 13 weeks of treatment).
|
6.0%
3/50 • Number of events 3 • From Baseline (visit 1) until End of Study visit (up to 13 weeks of treatment).
|
|
Nervous system disorders
Dizziness
|
0.00%
0/48 • From Baseline (visit 1) until End of Study visit (up to 13 weeks of treatment).
|
9.8%
4/41 • Number of events 4 • From Baseline (visit 1) until End of Study visit (up to 13 weeks of treatment).
|
2.0%
1/50 • Number of events 1 • From Baseline (visit 1) until End of Study visit (up to 13 weeks of treatment).
|
|
General disorders
Fatigue
|
2.1%
1/48 • Number of events 1 • From Baseline (visit 1) until End of Study visit (up to 13 weeks of treatment).
|
0.00%
0/41 • From Baseline (visit 1) until End of Study visit (up to 13 weeks of treatment).
|
8.0%
4/50 • Number of events 4 • From Baseline (visit 1) until End of Study visit (up to 13 weeks of treatment).
|
|
Gastrointestinal disorders
Diarrhea
|
6.2%
3/48 • Number of events 3 • From Baseline (visit 1) until End of Study visit (up to 13 weeks of treatment).
|
9.8%
4/41 • Number of events 6 • From Baseline (visit 1) until End of Study visit (up to 13 weeks of treatment).
|
10.0%
5/50 • Number of events 5 • From Baseline (visit 1) until End of Study visit (up to 13 weeks of treatment).
|
|
Gastrointestinal disorders
Vomiting
|
6.2%
3/48 • Number of events 3 • From Baseline (visit 1) until End of Study visit (up to 13 weeks of treatment).
|
0.00%
0/41 • From Baseline (visit 1) until End of Study visit (up to 13 weeks of treatment).
|
2.0%
1/50 • Number of events 1 • From Baseline (visit 1) until End of Study visit (up to 13 weeks of treatment).
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/48 • From Baseline (visit 1) until End of Study visit (up to 13 weeks of treatment).
|
7.3%
3/41 • Number of events 3 • From Baseline (visit 1) until End of Study visit (up to 13 weeks of treatment).
|
4.0%
2/50 • Number of events 2 • From Baseline (visit 1) until End of Study visit (up to 13 weeks of treatment).
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/48 • From Baseline (visit 1) until End of Study visit (up to 13 weeks of treatment).
|
4.9%
2/41 • Number of events 2 • From Baseline (visit 1) until End of Study visit (up to 13 weeks of treatment).
|
6.0%
3/50 • Number of events 4 • From Baseline (visit 1) until End of Study visit (up to 13 weeks of treatment).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60