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

Conditions: Huntington's disease
MedDRA version: 14.1Level: PTClassification code 10070668Term: Huntington's diseaseSystem Organ Class: 10010331 - Congenital, familial and genetic disorders
Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Registration Number: EUCTR2011-001131-23-GB

Lead Sponsor: Siena Biotech SpA

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 144

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).

Are the trial subjects under 18? no
Number of subjects for this age range:
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 44

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.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: 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.;Secondary Objective: 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. ;Primary end point(s): Outcome measures:<br>• Type and frequency of AEs<br>• Clinical laboratory tests (haematology, serum, biochemistry, and urinalysis)<br>• 12-lead ECG<br>• Physical and neurological examination findings<br>• Vital signs<br>• Suicide risk and suicide-related events (behaviour and/or ideation) as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)<br>;Timepoint(s) of evaluation of this end point: The primary endpoints will be evaluated throughout the duration of the study.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Outcome measures:<br>• Clinical Impression<br>• Global Clinical Impression (GCI) (patient and clinician-based)<br>• UHDRS Total Motor Scale<br>• Functional Assessment<br>• Independence Scale Assessment<br>• Problem Behaviours Assessment <br>• Cognitive Battery (Symbol Digit Modalities Test, Stroop Word Test, Verbal fluency, Mini-Mental State Examination [MMSE])<br>• Change from baseline levels of soluble Htt<br>• Change from baseline in acetylation status of mutant Htt<br>• 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-t), AUC from time zero to the last quantifiable concentration (AUC0-last), inter-patient and intra-patient variability.<br>;Timepoint(s) of evaluation of this end point: The secondary endpoints will be evaluated throughout the duration of the study.

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