Clinical Trials Register

Summary
EudraCT Number:	2011-001131-23
Sponsor's Protocol Code Number:	S015-002
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-06-27
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2011-001131-23

A.3

Full title of the trial

A double-blind, placebo-controlled study in Huntington’s Disease patients to determine the safety and tolerability of SEN0014196

A.3.1

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

A study to determine how safe and tolerable the study drug is, when given to patients with Huntingtons Disease.

A.3.2

Name or abbreviated title of the trial where available

N/A

A.4.1

Sponsor's protocol code number

S015-002

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	Siena Biotech SpA
B.1.3.4	Country	Italy
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	Siena Biotech SpA
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	ICON Clinical Research
B.5.2	Functional name of contact point	S015-002 Study Helpdesk
B.5.3	Address:
B.5.3.1	Street Address	Gustav III Boulevard 34, 5th Floor PO Box 728
B.5.3.2	Town/ city	Solna, Stockholm
B.5.3.3	Post code	16927
B.5.3.4	Country	Sweden
B.5.4	Telephone number	+46851484700
B.5.5	Fax number	+46850334680
B.5.6	E-mail	siena.helpdesk@iconplc.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	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/09/681
D.3 Description of the IMP
D.3.1	Product name	SEN0014196
D.3.2	Product code	SEN0014196
D.3.4	Pharmaceutical form	Tablet
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	selisistat
D.3.9.1	CAS number	49843-98-3
D.3.9.2	Current sponsor code	SEN0014196
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	50
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	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/09/681
D.3 Description of the IMP
D.3.1	Product name	SEN0014196
D.3.2	Product code	SEN0014196
D.3.4	Pharmaceutical form	Tablet
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	selisistat
D.3.9.1	CAS number	49843-98-3
D.3.9.2	Current sponsor code	SEN0014196
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	100
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	Tablet
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

E.1.1.1

Medical condition in easily understood language

Huntington's disease is a disorder of the central nervous system that causes progressive degeneration of cells in the brain, slowly impairing a person's ability to walk, think, talk and reason.

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	14.1
E.1.2	Level	PT
E.1.2	Classification code	10070668
E.1.2	Term	Huntington's disease
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

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

Main objective of the trial is to assess the safety and tolerability of 12 weeks treatment of SEN0014196 at doses of 50 mg and 200 mg once (qd) daily in Huntington’s disease (HD) patients.

E.2.2

Secondary objectives of the trial

Secondary objectives of the trials are to assess short-term clinical effects, modulation of candidate pharmacodynamic markers and the pharmacokinetic (PK) profile of 50 mg and 200 mg qd doses of SEN0014196 in HD patients treated for 12 weeks.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Genetically confirmed, manifest HD (CAG repeat length ≥ 36) and motor signs of HD (including motor score of the UHDRS ≥ 5).
2. Clinical Stages I to III (TFC of ≥ 3).
3. Patients must be anticipated to be ambulatory and able to attend outpatient visits for the duration of the study.
4. Patients must be aged ≥ 30 years and ≤ 70 years.
5. Body mass index between 18 and 31 kg/m2 inclusive, and a body weight greater than 50 kg.
6. Patients must be able to give informed consent or have a legal representative who can consent on their behalf. Patients must be able to comply with trial procedures.
7. Patients must have no clinically significant and relevant medical or psychiatric history that could affect the conduct of the study and evaluation of the data, as ascertained by the Investigator through detailed medical history and screening assessments.
8. Male patients must agree to use condoms during the entire duration of the study and for 3 months following the last dose of study drug.
9. Females of childbearing potential (last menses less than 1 year prior to enrolment):
• Must have a negative pregnancy test at Screening and at Baseline (Day 1).
• Must not be breastfeeding.
• Must either be surgically sterile (hysterectomy, bilateral oophorectomy, or tubal ligation), postmenopausal (cessation of menses for at least 1 year), or agree to use a medically accepted, highly effective method of contraception during the entire duration of the study and for 3 months after the last dose of the study drug. An effective method of birth control is defined as those methods, either alone or in combination, which have a low failure rate when used consistently and correctly, such as implants, injectables, combined oral contraceptives, non-hormonal intrauterine devices, sexual abstinence, a vasectomised partner or use of a double-barrier contraception method (eg, condom with diaphragm/occlusive cap and spermicide cream).

E.4

Principal exclusion criteria

1. Participation in a study with an investigational drug within 30 days of the Baseline Visit.
2. Any prior or concomitant use of Class I or Class II HDAC inhibitors such as Zolinza®/vorinostat or belinostat.
3. Clinical evidence of significant or unstable medical illness in the Investigator's judgement, including screening transaminases (AST or ALT) ≥ 1.5 times the ULN, or an estimated glomerular filtration rate (GFR) (modification of diet in renal disease [MDRD] equation) of < 60 mL/min, or unexplained proteinuria or microscopic haematuria in an uncontaminated sample obtained at Screening and confirmed on repeat testing. 4. QTcF interval >450 ms in men and >470 ms in women or PR >220 ms, or other clinically relevant abnormal ECG findings that, in the Investigator’s judgement, would present an unacceptable risk to patient safety.
5. Women who are pregnant or breastfeeding.
6. Clinically significant abnormalities in the screening laboratory studies which, in the opinion of the Investigator, would interfere with participation in the study.
7. Current evidence or history (within 1 year of baseline) of psychosis, hallucinations or delusions, including major depression with psychotic features, as defined in the Diagnostic and Statistical Manual, Fourth Edition, Text Revision (DSM-IV-TR). Patients currently experiencing mild depression, or moderate depression which is adequately and appropriately treated, in the judgement of the Investigator, can participate if depression is not expected to interfere with study participation.
8. Suicide risk, as determined by meeting any of the following criteria:
• A suicide attempt within the past year or suicidal ideation within 60 days of the Baseline Visit (Day 1)
• Significant risk of suicide, as judged by the Principal Investigator, based on the psychiatric interview or information collected in the C-SSRS
9. Current diagnosis or history (within 1 year of baseline) of any alcohol or substance abuse (except nicotine and caffeine-related disorders) as defined in the DSM-IV-TR.
10. Known allergy to any ingredient in the study drug (active and/or placebo).
11. A history of malignancy of any type within 2 years prior to screening. A history of surgically excised non-melanoma skin cancers is permitted.
12. Any relevant condition, behaviour, laboratory value, or concomitant medication which, in the opinion of the Investigator, makes the patient unsuitable for entry into the study.

Following pre-dose assessments, patients may be excluded from the study also for the following reasons:
• Intercurrent illness or clinically significant AEs
• Positive urine drug screen or alcohol breath test result which suggests substance abuse, and is not explained on the basis of prescription or over-the-counter medication which was used according to instruction.

E.5 End points

E.5.1

Primary end point(s)

Outcome measures:
• Type and frequency of AEs
• Clinical laboratory tests (haematology, serum, biochemistry, and urinalysis)
• 12-lead ECG
• Physical and neurological examination findings
• Vital signs
• Suicide risk and suicide-related events (behaviour and/or ideation) as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)

E.5.1.1

Timepoint(s) of evaluation of this end point

The primary endpoints will be evaluated throughout the duration of the study.

E.5.2

Secondary end point(s)

Outcome measures:
• Clinical Impression
• Global Clinical Impression (GCI) (patient and clinician-based)
• UHDRS Total Motor Scale
• Functional Assessment
• Independence Scale Assessment
• Problem Behaviours Assessment
• Cognitive Battery (Symbol Digit Modalities Test, Stroop Word Test, Verbal fluency, Mini-Mental State Examination [MMSE])
• Change from baseline levels of soluble Htt
• Change from baseline in acetylation status of mutant Htt
• Pharmacokinetics of SEN0014196 at steady state with the maximum observed plasma concentration (Cmax) time of maximum observed plasma concentration, (tmax), AUC from time zero to the length of the dosing interval (tau) (AUC0-τ), AUC from time zero to the last quantifiable concentration (AUC0-last), inter-patient and intra-patient variability.

E.5.2.1

Timepoint(s) of evaluation of this end point

The secondary endpoints will be evaluated throughout the duration of the study.

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

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Tolerability

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.8.5

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

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

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

The end of the trial is defined as the last visit of the last subject undergoing the trial.

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

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

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:

100

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

144

F.4.2.2

In the whole clinical trial

144

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)

After the end of the trial, patients will not receive the study drug. Patients will receive standard of care for their disease condition.

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
G.4.3.4	Network Country	France

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2011-09-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-09-19

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2012-09-18

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials