Efficacy and Safety on SOM3355 in Huntington's Disease Chorea

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Huntington Chorea

Intervention / Treatment
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* Drug: SOM3355 capsules
* Drug: Placebo capsules


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females ≥21 years old. Patients with a diagnosis of Huntington's Disease determined by a movement disorders expert and confirmed by a number of HTT gene CAG repeats ≥36. UHDRS® Total maximal chorea (TMC) score ≥10. UHDRS® Total Functional Capacity (TFC) ≥7. Able to walk independently or with minimal assistance. Females of child-bearing potential must use a medically accepted effective method of birth control and should not be breast-feeding. In the opinion of the Investigator, the patient must have adequate support to comply with the entire study requirements. Able and willing to provide written informed consent. Exclusion Criteria: Onset of HD symptoms prior to age of 21 years (juvenile forms of HD). HD patients presenting rigid akinesia. Use of other VMAT2 inhibitors such as tetrabenazine, deutetrabenazine, or valbenazine; and use of other antichoreic treatment such as any neuroleptic, or amantadine, memantine, riluzole. Patients who experienced severe depression or suicide attempt in the last 5 years. Severe untreated or under-treated psychiatric illness such as active suicidal ideation or behavior or depression. Patients with a history of, or current, hypotension, bradycardia, or orthostatic hypotension. Patients with hypertension already treated with more than 2 antihypertensive drugs. Other active clinically significant illness, which could interfere with the study conduct, counter-indicate the study treatment, place the patient at risk during the trial, or compromise their study participation. Any significant serious abnormality in the electrocardiogram (ECG), or a known history of long QTc syndrome. Patients with severe hepatic impairment, or with severe renal impairment, or with any other significant abnormality in the physical examination or clinical laboratory results that, in the Investigator's opinion, would not be compatible with study participation or represent a risk for the patient while in the study. Females who are pregnant or lactating, or who intend to become pregnant during the study period. Patients with allergy under desensitization, with known psoriasis, or a known allergy/hypersensitivity to any ingredients of the trial medication or placebo. History of alcohol or substance abuse in the previous 12 months. Patients participating in any other study, and the use of any investigational therapy.

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SOM3355 300 mg BID<br>Administration of SOM3355 in up-titration for 3 weeks up to the maintenance dose of 300 mg BID (twice daily) administered for 7 additional weeks, and down-titration for 2 weeks. | Drug: SOM3355 capsules<br>* Treatment will be blind for the whole duration of the study.<br>* Other names: Bevantolol hydrochloride;|
| Experimental: SOM3355 200 mg BID<br>Administration of SOM3355 in up-titration for 2 weeks up to the maintenance dose of 200 mg BID (twice daily) administered for 8 additional weeks, and down-titration for 2 weeks. | Drug: SOM3355 capsules<br>* Treatment will be blind for the whole duration of the study.<br>* Other names: Bevantolol hydrochloride;|
| Placebo Comparator: Placebo BID<br>Administration of matching Placebo BID (twice daily) for 12 weeks. | Drug: Placebo capsules<br>* Treatment will be blind for the whole duration of the study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Total Maximal Chorea (TMC) score of the UHDRS® | Total Maximal Chorea score of the Unified Huntington Disease Rating Scale is 0-28 and decrease means improvement. | Between baseline and end of maintenance dose (after 10 weeks of treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Clinical Global Impression (CGI) |  | Between baseline and end of maintenance dose (after 10 weeks of treatment) | 
| Change in the Patient Global Impression (PGI) |  | Between baseline and end of maintenance dose (after 10 weeks of treatment) | 
| TMC-response defined as improvement ≥2 in TMC score |  | Between baseline and end of maintenance dose (after 10 weeks of treatment) | 
| Percentage of change in TMC score |  | Between baseline and end of maintenance dose (after 10 weeks of treatment) | 
| Change in the Total Motor Score (TMS) of the UHDRS® | Total Motor Score is 0-124 and decrease means improvement. | Between baseline and end of maintenance dose (after 10 weeks of treatment) | 
| Change in the Gait sub-score of the UHDRS® |  | Between baseline and end of maintenance dose (after 10 weeks of treatment) | 
| Change in the Dystonia sub-score of the UHDRS® |  | Between baseline and end of maintenance dose (after 10 weeks of treatment) | 
| Change in the European Quality of Life scale (EQ-5D-5L) |  | Between baseline and end of maintenance dose (after 10 weeks of treatment) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Huntington, Chorea, SOM3355