Huntington Chorea
Conditions
Keywords
Huntington, Chorea, SOM3355
Brief summary
Phase IIb, randomized, double-blind, placebo-controlled study in parallel groups assessing the efficacy and safety of two doses of SOM3355 in patients suffering from Huntington's Disease with choreic movements.
Interventions
DRUGPlacebo capsules
Treatment was blind for the whole duration of the study.
DRUGSOM3355 200 mg capsules
Treatment was blind for the whole duration of the study.
DRUGSOM3355 300 mg capsules
Treatment was blind for the whole duration of the study.
Sponsors
SOM Innovation Biotech SA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Males or females ≥21 years old, a diagnosis of Huntington's Disease determined by a movement disorders expert and confirmed by a number of HTT gene CAG repeats ≥36, a UHDRS® Total maximal chorea (TMC) score ≥10, and a UHDRS® Total Functional Capacity (TFC) ≥7.
Exclusion criteria
Onset of HD symptoms prior to age of 21 years (juvenile forms of HD), HD patients presenting rigid akinesia, and use of other VMAT2 inhibitors such as tetrabenazine, deutetrabenazine, or valbenazine, or other antichoreic treatment such as any neuroleptic, or amantadine, memantine, riluzole.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Total Maximal Chorea (TMC) Score of the UHDRS® for Subjects Not Taking Neuroleptics During the Trial (mITT - N=122) | From baseline to end of maintenance dose (10 weeks of treatment). | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Clinical Global Impression (CGI) (mITT - N=139) | From baseline to end of maintenance dose (10 weeks of treatment). | 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. |
| Change in the Patient Global Impression (PGI) (mITT - N=139) | From baseline to end of maintenance dose (10 weeks of treatment). | 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. |
Countries
France, Germany, Italy, Poland, Spain, Switzerland, United Kingdom
Participant flow
Recruitment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 48 |
| 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. | 41 |
| 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. | 50 |
| Total | 139 |
Baseline characteristics
| Characteristic | Placebo | Total | SOM3355 600 mg/Day | SOM3355 400 mg/Day |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 19 Participants | 5 Participants | 9 Participants |
| Age, Categorical Between 18 and 65 years | 43 Participants | 120 Participants | 45 Participants | 32 Participants |
| Age, Continuous | 51.65 years STANDARD_DEVIATION 10.46 | 51.79 years STANDARD_DEVIATION 11.58 | 51.34 years STANDARD_DEVIATION 12.12 | 52.51 years STANDARD_DEVIATION 12.39 |
| Race/Ethnicity, Customized Ethnic Origin African (North) | 0 Participants | 2 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Ethnic Origin Latino | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Ethnic Origin Other (in France) | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Ethnic Origin White | 48 Participants | 135 Participants | 48 Participants | 39 Participants |
| Region of Enrollment France | 7 participants | 15 participants | 6 participants | 2 participants |
| Region of Enrollment Germany | 7 participants | 21 participants | 7 participants | 7 participants |
| Region of Enrollment Italy | 5 participants | 19 participants | 8 participants | 6 participants |
| Region of Enrollment Poland | 8 participants | 26 participants | 9 participants | 9 participants |
| Region of Enrollment Spain | 12 participants | 35 participants | 11 participants | 12 participants |
| Region of Enrollment Switzerland | 2 participants | 5 participants | 2 participants | 1 participants |
| Region of Enrollment United Kingdom | 7 participants | 18 participants | 7 participants | 4 participants |
| Sex: Female, Male Female | 28 Participants | 66 Participants | 21 Participants | 17 Participants |
| Sex: Female, Male Male | 20 Participants | 73 Participants | 29 Participants | 24 Participants |
| Total Maximal Chorea (TMC) score | 12.80 units on a scale STANDARD_DEVIATION 2.58 | 12.94 units on a scale STANDARD_DEVIATION 2.77 | 13.23 units on a scale STANDARD_DEVIATION 2.84 | 12.74 units on a scale STANDARD_DEVIATION 2.93 |
| Use of Neuroleptics No | 42 Participants | 122 Participants | 44 Participants | 36 Participants |
| Use of Neuroleptics Yes | 6 Participants | 17 Participants | 6 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 48 | 0 / 41 | 0 / 50 |
| other Total, other adverse events | 10 / 48 | 15 / 41 | 22 / 50 |
| serious Total, serious adverse events | 1 / 48 | 1 / 41 | 1 / 50 |
Outcome results
Primary
Change in Total Maximal Chorea (TMC) Score of the UHDRS® for Subjects Not Taking Neuroleptics During the Trial (mITT - N=122)
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.
Time frame: 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).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | 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 |
| SOM3355 400 mg/Day | Change in Total Maximal Chorea (TMC) Score of the UHDRS® for Subjects Not Taking Neuroleptics During the Trial (mITT - N=122) | -2.42 units on a scale |
| SOM3355 600 mg/Day | Change in Total Maximal Chorea (TMC) Score of the UHDRS® for Subjects Not Taking Neuroleptics During the Trial (mITT - N=122) | -3.46 units on a scale |
p-value: =0.04595% CI: [-2.51, -0.03]Mixed Models Analysis
Secondary
Change in the Clinical Global Impression (CGI) (mITT - N=139)
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.
Time frame: 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.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Change in the Clinical Global Impression (CGI) (mITT - N=139) | Not Improved | 26 Participants |
| Placebo | Change in the Clinical Global Impression (CGI) (mITT - N=139) | Improved | 15 Participants |
| SOM3355 400 mg/Day | Change in the Clinical Global Impression (CGI) (mITT - N=139) | Improved | 26 Participants |
| SOM3355 400 mg/Day | Change in the Clinical Global Impression (CGI) (mITT - N=139) | Not Improved | 11 Participants |
| SOM3355 600 mg/Day | Change in the Clinical Global Impression (CGI) (mITT - N=139) | Improved | 23 Participants |
| SOM3355 600 mg/Day | Change in the Clinical Global Impression (CGI) (mITT - N=139) | Not Improved | 18 Participants |
p-value: =0.07895% CI: [0.91, 5.37]Regression, Logistic
Secondary
Change in the Patient Global Impression (PGI) (mITT - N=139)
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.
Time frame: 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.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Change in the Patient Global Impression (PGI) (mITT - N=139) | Improved | 20 Participants |
| Placebo | Change in the Patient Global Impression (PGI) (mITT - N=139) | Not Improved | 21 Participants |
| SOM3355 400 mg/Day | Change in the Patient Global Impression (PGI) (mITT - N=139) | Improved | 25 Participants |
| SOM3355 400 mg/Day | Change in the Patient Global Impression (PGI) (mITT - N=139) | Not Improved | 12 Participants |
| SOM3355 600 mg/Day | Change in the Patient Global Impression (PGI) (mITT - N=139) | Improved | 26 Participants |
| SOM3355 600 mg/Day | Change in the Patient Global Impression (PGI) (mITT - N=139) | Not Improved | 14 Participants |
p-value: 0.14395% CI: [0.8, 4.76]Regression, Logistic
Post Hoc
Change in Total Maximal Chorea (TMC) Score for Subjects Not Taking Neuroleptics and With Mean Baseline TMC Score >12 (mITT - N=57)
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | 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 |
| SOM3355 400 mg/Day | Change in Total Maximal Chorea (TMC) Score for Subjects Not Taking Neuroleptics and With Mean Baseline TMC Score >12 (mITT - N=57) | -2.76 units on a scale |
| SOM3355 600 mg/Day | Change in Total Maximal Chorea (TMC) Score for Subjects Not Taking Neuroleptics and With Mean Baseline TMC Score >12 (mITT - N=57) | -4.21 units on a scale |
p-value: =0.03295% CI: [-3.4, -0.16]Mixed Models Analysis