A Phase II Safety and Tolerability Study With SEN0014196

A Double-blind, Placebo-controlled Study in Huntington's Disease Patients to Determine the Safety and Tolerability of SEN0014196

The principal aim of this study is to obtain safety and tolerability data when SEN0014196 is administered orally over 12 weeks to male and female patients with Huntington's Disease.

Study Overview

• Status: Completed
• Conditions: Huntington's Disease
• Intervention / Treatment: Drug: SEN0014196; Drug: SEN0014196; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 144
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Münster, Germany, 48149
    • Dept. of Neurology, University of Münster

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Genetically confirmed, manifest HD (CAG repeat length ≥ 36) and motor signs of HD (including motor score of the UHDRS ≥ 5).
• Clinical Stages I to III (Total Functional Capacity Subscale Score [TFC] of ≥ 3).
• Patients must be anticipated to be ambulatory and able to attend outpatient visits for the duration of the study.
• Patients must be aged ≥ 30 years and ≤ 70 years.
• Body mass index between 18 and 31 kg/m2 inclusive, and a body weight greater than 50 kg.
• 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.
• 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.
• 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.
• Females of childbearing potential (last menses less than 1 year prior to enrolment).

Exclusion Criteria:

• Participation in a study with an investigational drug within 30 days of the Baseline Visit.
• Any prior or concomitant use of Class I or Class II histone deacetylase (HDAC) inhibitors such as Zolinza®/vorinostat or belinostat.
• Clinical evidence of significant or unstable medical illness in the Investigator's judgement, including screening transaminases (AST or ALT) ≥ 3 times the upper limit of normal (ULN), or an estimated GFR < 60 mL/min, or unexplained proteinuria or microscopic haematuria in an uncontaminated sample obtained at Screening and confirmed on repeat testing.
• QTcF interval >450 ms in men and >470 ms in women or PR >220 ms, or other clinically relevant abnormal ECG findings
• Women who are pregnant or breastfeeding.
• Clinically significant abnormalities in the screening laboratory studies which, in the opinion of the Investigator, would interfere with participation in the study.
• Current evidence or history (within 1 year of baseline) of psychosis, hallucinations or delusions, including major depression with psychotic features, as defined in the DSM-IV-TR. Patients currently experiencing mild depression, or moderate depression which is adequately and appropriately treated in the judgment of the Investigator, can participate if depression is not expected to interfere with study participation.

• 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.
• 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.
• Known allergy to any ingredient in the study drug (active and/or placebo).
• A history of malignancy of any type within 2 years prior to screening. A history of surgically excised non-melanoma skin cancers is permitted.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo tablet	Drug: Placebo; oral once daily tablet
Experimental: SEN0014196 50 mg oral tablet	Drug: SEN0014196; 50 mg oral once daily tablet; Drug: SEN0014196; 200 mg oral once daily tablet
Experimental: SEN0014196 200 mg oral tablet	Drug: SEN0014196; 50 mg oral once daily tablet; Drug: SEN0014196; 200 mg oral once daily tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability	Adverse event (AE) reporting, 12-lead electrocardiogram (ECG), vital signs, physical examination findings, and laboratory safety tests. Suicide risk (Columbia Suicide Severity Rating Scale,C-SSRS).	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Short-term clinical effects	Global Clinical Impression (GCI, patient and clinician-based), UHDRS, Total Motor Scale (UHDRS-TMS), Functional Assessment, Independence Scale Assessment, Problem Behaviours Assessment, Cognitive Battery (Symbol Digit Modalities Test, Stroop Word Test, Verbal fluency, Mini-Mental State Examination [MMSE]).	12 weeks
Modulation of candidate pharmacodynamic markers	Acetylation status of mutant huntingtin, levels of soluble huntingtin.	12 weeks
Pharmacokinetic profile		12 weeks

Collaborators and Investigators

• Sponsor: Siena Biotech S.p.A.
• Investigators: Principal Investigator: Ralf Reilmann, MD, Dept. of Neurology, University of Münster - Germany

Publications and helpful links

Helpful Links

• The European Huntington's Disease Network

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: January 26, 2012
• First Submitted That Met QC Criteria: January 26, 2012
• First Posted (Estimate): January 30, 2012

Study Record Updates

• Last Update Posted (Estimate): November 25, 2015
• Last Update Submitted That Met QC Criteria: November 24, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Dyskinesias; Heredodegenerative Disorders, Nervous System; Dementia; Cognition Disorders; Chorea; Huntington Disease
• Other Study ID Numbers: S015-002