A Phase II Safety and Tolerability Study With SEN0014196

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Siena Biotech S.p.A.
ClinicalTrials.gov Identifier:
NCT01521585
First received: January 26, 2012
Last updated: November 13, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
Huntington's Disease
Drug: SEN0014196
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-blind, Placebo-controlled Study in Huntington's Disease Patients to Determine the Safety and Tolerability of SEN0014196

Resource links provided by NLM:


Further study details as provided by Siena Biotech S.p.A.:

Primary Outcome Measures:
  • Safety and tolerability [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    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).


Secondary Outcome Measures:
  • Short-term clinical effects [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    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]).

  • Modulation of candidate pharmacodynamic markers [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Acetylation status of mutant huntingtin, levels of soluble huntingtin.

  • Pharmacokinetic profile [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Enrollment: 144
Study Start Date: November 2011
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SEN0014196 oral tablet Drug: SEN0014196
50 mg oral once daily tablet
Experimental: SEN0014196 oral tablet Drug: SEN0014196
200 mg oral once daily tablet
Placebo Comparator: Placebo Drug: Placebo
oral once daily tablet

  Eligibility

Ages Eligible for Study:   30 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01521585

Locations
Germany
Dept. of Neurology, University of Münster
Münster, Germany, 48149
Sponsors and Collaborators
Siena Biotech S.p.A.
Investigators
Principal Investigator: Ralf Reilmann, MD Dept. of Neurology, University of Münster - Germany
  More Information

Additional Information:
No publications provided

Responsible Party: Siena Biotech S.p.A.
ClinicalTrials.gov Identifier: NCT01521585     History of Changes
Other Study ID Numbers: S015-002
Study First Received: January 26, 2012
Last Updated: November 13, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Huntington Disease
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Dementia
Chorea
Dyskinesias
Movement Disorders
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Cognition Disorders
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders

ClinicalTrials.gov processed this record on October 19, 2014