Study to Measure Cerebrospinal Fluid Mutant Huntingtin Protein in Participants With Early Manifest Stage I or Stage II Huntington's Disease

A Multi-Site, Prospective, Longitudinal, Cohort Study Measuring Cerebrospinal Fluid-Mutant Huntingtin Protein in Patients With Huntington's Disease

The study is designed as a multi-site, prospective, 15-month longitudinal, cohort study measuring CSF mHTT in participants with early manifest Stage I or Stage II Huntington's Disease (HD).

Study Overview

• Status: Completed
• Conditions: Huntington's Disease
• Intervention / Treatment: Other: No Study Drug was Administered in this Study

• Study Type: Interventional
• Enrollment (Actual): 95
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6T 2B5
      • The University of British Columbia; The Centre for Huntington Disease
  • Ontario
    • Markham, Ontario, Canada, L6B 1C9
      • Centre for Movement Disorders (Neuropharm Consulting Inc.)
• Germany
  • Berlin, Germany, 10117
    • Charité - Universitätsmedizin Berlin, Campus Charité Mitte; Klinik für Psychiatrie und Psychotherapi
  • Bochum, Germany, 44791
    • St. Josef and St. Elisabeth gGmbH ; St. Josef Hospital Bochum; Neurologisches Forschungszentrum
  • Ulm, Germany, 89081
    • Universitätsklinikum Ulm; Klinik für Neurologie
• United Kingdom
  • Birmingham, United Kingdom, B15 2FG
    • NIHR Welcome Trust Birmingham CRF - University Hospitals Birmingham; Department of Neuropsychiatry
  • Cardiff, United Kingdom, CF24 4HQ
    • Cardiff University School of Medicine; Institute of Psychological Medicine Clinical Neurosciences
  • London, United Kingdom, WC1N 3BG
    • National Hospital For Neurology and Neurosurgery
  • Manchester, United Kingdom, M13 9WL
    • Central Manchester University Hospitals NHS Foundation Trust; Manchester Centre for Genomic Medicine
• United States
  • Colorado
    • Englewood, Colorado, United States, 80113
      • Rocky Mountain Movement Disorders Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University; Research Division, Psychiatry
  • Kansas
    • Wichita, Kansas, United States, 67226
      • Hereditary Neurological Disease Centre (HNDC)
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • John Hopkins University School of Medicine
  • New York
    • New York, New York, United States, 10032-3725
      • Columbia University
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas Health Science Center at Houston; McGovern Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Capacity to consent to participate in the study as assessed using the Evaluation to Sign Consent tool and investigator judgment
• Age 25 to 65 years, inclusive, at the time of signing Informed Consent Form
• Early manifest, Stage I or Stage II HD (defined as TFC of 7-13, inclusive)
• Genetically confirmed disease (CAG repeat length ≥ 36 in huntingtin gene by direct DNA testing)
• Body mass index ≥18 and ≤32 kg/m2; total body weight >50 kg
• Ability to undergo and tolerate MRI scans
• Ability to tolerate blood draws and lumbar puncture
• Ability and willingness to comply with all aspects of the protocol, including completion of interviews and questionnaires and carrying/wearing of a digital monitoring device
• Stable medical, psychiatric, and neurological status for at least 12 weeks prior to screening and at the time of enrollment
• Signed study companion consent for participation, if a study companion is available
• For women of childbearing potential: agreement to remain abstinent or use acceptable contraceptive methods during the observational period

Exclusion Criteria:

• Any condition, including severe chorea, that would prevent either writing or performing pen and paper or smartphone-based tasks
• History of attempted suicide or suicidal ideation with plan (i.e., active suicidal ideation) that required hospital visit and/or change in level of care within 12 months prior to screening
• Current active psychosis, confusional state, or violent behavior
• Any serious medical condition or clinically significant laboratory, vital sign, or electrocardiogram abnormalities at screening that, in the investigator's judgement, precludes the participant's safe participation in and completion of the study
• Pregnant or breastfeeding, or intending to become pregnant during the study
• Positive for hepatitis C virus antibody or hepatitis B surface antigen at screening
• Known HIV infection
• Current or previous use of an antisense oligonucleotide (including small interfering RNA)
• Current use of antipsychotics prescribed for psychosis, cholinesterase inhibitors, memantine, amantadine, or riluzole including use within 12 weeks of enrollment
• Treatment with an investigational drug within 30 days prior to screening or 5 half-lives of the investigational drug, whichever is longer
• Antiplatelet or anticoagulant therapy within the 14 days prior to screening or anticipated use during the study, including, but not limited, to aspirin (unless ≤81mg/day), clopidogrel, dipyridamole, warfarin, dabigatran, rivaroxaban, and apixaban
• History of bleeding diathesis or coagulopathy; platelet count < lower limit of normal unless stable and assessed by the Investigator and Sponsor Medical Monitor to be not clinically significant
• Malignancy within 5 years prior to screening, except basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated
• History of gene therapy or cell transplantation or any other experimental brain surgery
• Concurrent or planned concurrent participation in any clinical study without approval of the Medical Monitor
• Presence of implanted shunt for the drainage of CSF or an implanted CNS catheter
• Pre-existing structural brain lesion as assessed by MRI scan

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Participants with Early Manifest Stage I or II HD; No study drug was administered in this study	Other: No Study Drug was Administered in this Study; No study drug was administered in this study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in the Following Clinical Endpoints at 3, 9, and 15 Months: cUHDRS, TFC, TMS, SDMT, SWR Test, and IS	cUHDRS = composite Unified Huntington's Disease Rating Scale TFC = Total Functional Capacity Scale TMS = Total Motor Scale SDMT = Symbol Digit Modalities Test SWR = Stroop Word Reading IS = Independence Scale	Baseline to 15 months
Change from Baseline in Biomarkers of Neuronal Injury (e.g., CSF NfL and tau) at 3, 9, and 15 Months	CSF = Cerebrospinal Fluid NfL = Neurofilament Light Chain	Baseline to 15 Months
Change from Baseline in Brain Atrophy Endpoints (e.g., Whole Brain Volume Decline, Caudate Volume Decline) as Determined by Brain MRI, at 3, 9, and 15 Months		Baseline to 15 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Within-Participant Change from Baseline in CSF mHTT Levels at 3, 9, and 15 Months	mHTT=Mutant Huntingtin Protein	Baseline to 15 Months
Association of Change from Baseline in Clinical Measures (cUHDRS, TFC, TMS, SDMT, SWR, and IS) at 3, 9, and 15 Months		Baseline to 15 Months
Association of Change from Baseline in Biomarkers of Neuronal Injury (e.g., CSF NfL and tau) at 3, 9, and 15 Months		Baseline to 15 Months
Association of Change from Baseline in Brain Atrophy Endpoints, as Determined by Brain MRI at 3, 9, and 15 Months		Baseline to 15 Months

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2018
• Primary Completion (Actual): May 7, 2021
• Study Completion (Actual): May 7, 2021

Study Registration Dates

• First Submitted: September 7, 2018
• First Submitted That Met QC Criteria: September 7, 2018
• First Posted (Actual): September 11, 2018

Study Record Updates

• Last Update Posted (Actual): October 27, 2021
• Last Update Submitted That Met QC Criteria: October 26, 2021
• Last Verified: October 1, 2021

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: BN40422

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No