Efficacy and Safety on SOM3355 in Huntington's Disease Chorea

Sponsor

SOM Innovation Biotech SA (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05475483

Collaborator

(none)

129

Enrollment

Locations

Arms

Anticipated Duration (Months)

5.9

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Huntington Chorea	Drug: SOM3355 capsules Drug: Placebo capsules	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

129 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Aug 1, 2022

Anticipated Primary Completion Date :

Mar 1, 2023

Anticipated Study Completion Date :

Jun 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SOM3355 300 mg BID 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 Treatment will be blind for the whole duration of the study. Other Names: Bevantolol hydrochloride
Experimental: SOM3355 200 mg BID 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 Treatment will be blind for the whole duration of the study. Other Names: Bevantolol hydrochloride
Placebo Comparator: Placebo BID Administration of matching Placebo BID (twice daily) for 12 weeks.	Drug: Placebo capsules Treatment will be blind for the whole duration of the study.

Arm

Intervention/Treatment

Experimental: SOM3355 300 mg BID

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

Treatment will be blind for the whole duration of the study.

Other Names:

Bevantolol hydrochloride

Experimental: SOM3355 200 mg BID

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

Treatment will be blind for the whole duration of the study.

Other Names:

Bevantolol hydrochloride

Placebo Comparator: Placebo BID

Administration of matching Placebo BID (twice daily) for 12 weeks.

Drug: Placebo capsules

Treatment will be blind for the whole duration of the study.

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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® [Between baseline and end of maintenance dose (after 10 weeks of treatment)]
Total Motor Score is 0-124 and decrease means improvement.
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)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	Country
1	Centre Hospitalier Universitaire Angers	Angers	France
2	CHU Hôpital Henri Mondor (APHP)	Créteil	France
3	Hôpital Roger Salengro - CHU Lille	Lille	France
4	Hopital de Hautepierre	Strasbourg	France
5	Hôpital Purpan - CHU Toulouse	Toulouse	France
6	Charité - Universitätsmedizin Berlin	Berlin	Germany
7	George Huntington Institut	Münster	Germany
8	Hospital of University of Ulm	Ulm	Germany
9	IRCCS Istituto delle Scienze Neurologiche di Bologna	Bologna	Italy
10	Azienda Ospedaliera Universitaria Federico II	Napoli	Italy
11	IRCCS Casa Sollievo della Sofferenza	Roma	Italy
12	Sant'Andrea University Hospital	Roma	Italy
13	Krakowska Akademia Neurologii Sp. z o.o.	Kraków	Poland
14	Indywidualna Praktyka Lekarska Daniel Zielonka	Poznań	Poland
15	Hospital de la Santa Creu i Sant Pau	Barcelona	Spain
16	Hospital Universitario de Cruces	Bilbao	Spain
17	Hospital Universitario de Burgos	Burgos	Spain
18	Hospital Ramón y Cajal	Madrid	Spain
19	Universitaetsspital Bern - Inselspital	Bern	Switzerland
20	Cambridge University Hospitals NHS Foundation Trust Addenbrooke's Hospital	Cambridge	United Kingdom
21	NIHR Wellcome Trust Manchester Clinical Research Facility	Manchester	United Kingdom
22	Oxford University Hospitals NHS Foundation Trust	Oxford	United Kingdom