Clinical Trials Register

Summary
EudraCT Number:	2021-003453-28
Sponsor's Protocol Code Number:	SOMCT03
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2021-12-31
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

France - ANSM

A.2

EudraCT number

2021-003453-28

A.3

Full title of the trial

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.

Étude de phase IIb, randomisée, en double aveugle, contre placebo, en groupes parallèles, visant à évaluer l’efficacité et la sécurité de deux doses de SOM3355 chez des patients souffrant de la maladie de Huntington avec mouvements choréiques.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Phase IIb study assessing the efficacy and safety of two doses of SOM3355 in patients suffering from Huntington’s Disease with choreic movements.

A.4.1

Sponsor's protocol code number

SOMCT03

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	SOM Innovation Biotech SA (SOM Biotech)
B.1.3.4	Country	Spain
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	SOM Innovation Biotech SA (SOM Biotech)
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	SOM Innovation Biotech SA (SOM Biotech)
B.5.2	Functional name of contact point	Clinical Trial Information Desk
B.5.3	Address:
B.5.3.1	Street Address	Baldiri Reixac, 4
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08028
B.5.3.4	Country	Spain
B.5.4	Telephone number	+34934 020 150
B.5.6	E-mail	info@sombiotech.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Calvan (bevantolol hydrochloride)
D.2.1.1.2	Name of the Marketing Authorisation holder	Nippon Chemiphar
D.2.1.2	Country which granted the Marketing Authorisation	Japan
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	SOM3355 (bevantolol hydrochloride)
D.3.2	Product code	SOM3355
D.3.4	Pharmaceutical form	Capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	BEVANTOLOL HYDROCHLORIDE
D.3.9.1	CAS number	59170-23-9
D.3.9.2	Current sponsor code	SOM3355
D.3.9.4	EV Substance Code	SUB00793MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	200
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Calvan (bevantolol hydrochloride)
D.2.1.2	Country which granted the Marketing Authorisation	Japan
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	SOM3355 (bevantolol hydrochloride)
D.3.2	Product code	SOM3355
D.3.4	Pharmaceutical form	Capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	BEVANTOLOL HYDROCHLORIDE
D.3.9.1	CAS number	59170-23-9
D.3.9.2	Current sponsor code	SOM3355
D.3.9.4	EV Substance Code	SUB00793MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	300
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Huntington’s Disease with choreic movements.

E.1.1.1

Medical condition in easily understood language

Huntington’s Disease with choreic movements.

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10020469
E.1.2	Term	Huntington's chorea
E.1.2	System Organ Class	100000004850

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of the study is to assess the efficacy of two doses of SOM3355 (400 mg/day and 600 mg/day taken twice daily [BID] over at least 8 weeks at maintenance dose) compared to placebo to reduce chorea in HD patients measured by the change in TMC score (primary efficacy endpoint).

E.2.2

Secondary objectives of the trial

To evaluate the safety and tolerability of two doses of SOM3355 (400 mg/day and 600 mg/day taken) compared with placebo in HD patients, with particular attention to depression and suicidality and to the cardiovascular hemodynamic parameters.
And to evaluate the efficacy of the two doses of SOM3355 (400 mg/day and 600 mg/day taken BID) compared with placebo on:
the change of Clinical Global Impression (CGI C),
the change of Patient Global Impression (PGI-C),
the percentage of responders based on the improvement ≥2 in TMC score,
the percentage of change of TMC score.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

A PK sub-study will be conducted to characterize the PK profile of repeated doses of SOM3355 at 400 and 600 mg/day. This analysis will be performed by collecting 12-hour PK samples (H0, H0.5, H1, H1.5, H2, H3, H5, H8, and H12) in 8 patients per arm (24 patients in total) that will be hospitalized for 24 hours at Visit 2. In addition, cardiac and hemodynamic parameters will be collected in parallel, with 12-hour cardiac Holter and blood pressure measurements before each PK sample, to allow PK-PD modeling assessments. These patients will be recruited by 3 or 4 sites able to manage the logistics of PK sampling.

E.3

Principal inclusion criteria

1.Males or females ≥21 years old.
2.Patients with a diagnosis of Huntington’s Disease determined by a movement disorders expert and confirmed by a number of HTT gene cytosine-adenosine-guanine (CAG) repeats ≥36.
3.UHDRS Total maximal chorea (TMC) score ≥10.
4.UHDRS Total Functional Capacity (TFC) ≥7 (corresponding to mildly to moderately impaired patients).
5.Able to walk independently or with minimal assistance.
6.Females of child-bearing potential must use a medically accepted effective method of birth control, agree to continue this method for the duration of the study and for at least 1 month following the last dose of study drug, and be negative to serum pregnancy test performed at the screening visit. Female patients should not be breast-feeding.
7.In the opinion of the Investigator, the patient must have adequate support to comply with the entire study requirements as described in this protocol (e.g. transportation to and from the trial site, self-rating scales, drug compliance, scheduled visits, etc.).
8.Able and willing to provide written informed consent prior to any study-related procedure being performed at the screening visit.

E.4

Principal exclusion criteria

1. Onset of HD symptoms prior to age of 21 years, corresponding to juvenile forms of HD.
2.HD patients presenting rigid akinesia.
3.Use of other vesicular monoamine transporter type 2 (VMAT2) inhibitors such as tetrabenazine, deutetrabenazine, or valbenazine within 3 months before enrollment, and at any time during the study period; and use of other antichoreic treatment such as any neuroleptic within 2 months or amantadine, memantine, riluzole within 1 month before enrollment and along the study.
4.Patients who experienced severe depression or suicide attempt in the last 5 years.
5.Severe untreated or under-treated psychiatric illness such as active suicidal ideation or behavior (BDI-21 item #9 >0 and active suicidal ideation in C-SSRS) or depression at screening and/or initiation visit (BDI-21 items total score >30); although patients taking authorized antidepressant therapy at a stable dose for at least 2 months and stabilized can be enrolled.
6.Patients with a history of, or current, hypotension (SBP <110 mmHg), bradycardia (HR <50 bpm), or orthostatic hypotension as defined by the European Society of Hypertension (reduction in SBP ≥20 mmHg or in DBP ≥10 mmHg).
7.Patients with hypertension already treated with more than 2 antihypertensive drugs.
8.Other active clinically significant illness, including unstable cardiovascular disease, angina pectoris, congestive heart failure, pulmonary hypertension, peripheral arterial disease, history of pheochromocytoma, bronchial asthma, COPD, bronchospasm, idiopathic hypoglycemia, inadequately-controlled diabetes, diabetic ketoacidosis or metabolic acidosis, or neoplastic pathology notably prolactin-dependent tumors (e.g. pituitary or breast cancer), which could interfere with the study conduct, or counter-indicate the study treatment, or to place the patient at risk during the trial, or compromise their study participation.
9.Any significant serious abnormality in the electrocardiogram (ECG), e.g. recent myocardial infarction, significant sinus bradycardia (<50 bpm), atrioventricular block (grades I to III with PR >240msec), sinoatrial block, atrial sinus disease or prolonged QTc interval at screening (ECG Bazett’s corrected QT interval (QT / √ [HR/60] >450 msec for males or >470 msec for females), or a known history of long QTc syndrome.
10.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.
11.Females who are pregnant or lactating, or who intend to become pregnant during the study period.
12.Patients with allergy under desensitization, with known psoriasis, or a known allergy / hypersensitivity to any ingredients of the trial medication or placebo.
13.History of alcohol or substance abuse in the previous 12 months.
14.Patients participating in any other study, and the use of any investigational therapy, within 1 month prior to entry in this study.

E.5 End points

E.5.1

Primary end point(s)

Change in Total Maximal Chorea (TMC) sub-score of the Unified
Huntington's Disease Rating Scale (UHDRS)

E.5.1.1

Timepoint(s) of evaluation of this end point

Between baseline and end of maintenance dose

E.5.2

Secondary end point(s)

•Change from baseline in the Clinical Global Impression (CGI-C).
•Change from baseline in the Patient Global Impression (PGI-C).
•TMC-response defined as improvement ≥2 in TMC score between
baseline and end of maintenance dose.
•Percentage of change in TMC score between baseline and the end of
maintenance dose.
•Change from baseline in Total Motor Score (TMS) of the UHDRS.
•Change from baseline in Gait sub-score of the UHDRS.
•Change from baseline in Dystonia sub-score of the UHDRS.
•Change from baseline in EQ5D-5L measuring quality of life.

E.5.2.1

Timepoint(s) of evaluation of this end point

Between baseline and end of maintenance dose

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

France

Poland

Spain

Switzerland

Germany

Italy

United Kingdom

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LPLV

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

120

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

105

F.4.2.2

In the whole clinical trial

129

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Yes, an OLE study

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	European Huntington's Disease Network (EHDN)
G.4.3.4	Network Country	Germany

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2022-07-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-02-02

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2024-06-25

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