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

NCT03664804 | Completed Phase 1 Results

• 1 other identifier: BN40422
• Study Type: interventional
• Target: 95
• Locations: 4 countries
• Sites: 15

Brief Summary

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).

Conditions

Huntington's Disease

Outcome Measures

Primary Outcomes (3)

• Change From Baseline in the Following Clinical Endpoints at 3, 9, and 15 Months: cUHDRS, TFC, TMS, SDMT, SWR Test and IS

  The reported data are as follows: 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. cUHDRS: score range from -3.06 (worst) to not defined maximum (best); Stroop Word Reading Test: score range not defined, higher scores indicate better cognitive performance; Symbol Digit Modalities Test: score range from 0 (worst) to 110 (best); Total Functional Capacity: score range from 0 (worst) to 13 (best); Total Motor Scale: score range from 0 (best) to 124 (worst). Data at Month 3, 9, and 15 are reported respectively

  Baseline to 15 Months

• Change From Baseline in Biomarkers of Neuronal Injury (CSF NfL and Tau) at 3, 9, and 15 Months

  The reported date appreciations are as follows: CSF = Cerebrospinal Fluid; NfL = Neurofilament Light Chain. An overview of percentage change from baseline in geometric means for CSF tau and CSF NfL, and CSF YKL-40 are reported

  Baseline to 15 Months

• Change From Baseline in Brain Atrophy Endpoints (Whole Brain Volume Decline, Caudate Volume Decline) as Determined by Brain MRI, at 3, 9, and 15 Months

  Data for Least Square (LS) mean percentage change from baseline to Months 3, 9, and 15 for ventricular volume, caudate volume, and whole brain volume, based on boundary shift integrals (BSIs) are reported

  Baseline to 15 Months

Secondary Outcomes (4)

• Within-Participant Change From Baseline in CSF mHTT Levels at 3, 9, and 15 Months

  Baseline to 15 Months

• Association of Change From Baseline in Cerebrospinal Fluid (FSF) mHTT With Change From Baseline in Clinical Measure

  Baseline to 15 Months

• Association of Change From Baseline in Biomarkers of Neuronal Injury

  Baseline to 15 Months

• Association of Change From Baseline in Brain Atrophy Endpoints, as Determined by Brain MRI

  Baseline to 15 Months

Study Arms (1)

Participants with Early Manifest Stage I or II HD

OTHER

No study drug was administered in this study

Other: No Study Drug was Administered in this Study

Interventions

No Study Drug was Administered in this Study OTHER

No study drug was administered in this study

Participants with Early Manifest Stage I or II HD

Eligibility Criteria

• Age: 25 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (15)

CenExel Rocky Mountain Clinical Research, LLC

Englewood, Colorado, 80113, United States

Location

Georgetown University; Research Division, Psychiatry

Washington D.C., District of Columbia, 20007, United States

Location

Hereditary Neurological Disease Centre (HNDC)

Wichita, Kansas, 67226, United States

Location

John Hopkins University School of Medicine

Baltimore, Maryland, 21287, United States

Location

Columbia University

New York, New York, 10032-3725, United States

Location

The University of Texas Health Science Center at Houston; McGovern Medical School

Houston, Texas, 77030, United States

Location

The University of British Columbia; The Centre for Huntington Disease

Vancouver, British Columbia, V6T 2B5, Canada

Location

Centre for Movement Disorders (Neuropharm Consulting Inc.)

Markham, Ontario, L6B 1C9, Canada

Location

Charité - Universitätsmedizin Berlin, Campus Charité Mitte; Klinik für Psychiatrie und Psychotherapi

Berlin, 10117, Germany

Location

St. Josef and St. Elisabeth gGmbH ; St. Josef Hospital Bochum; Neurologisches Forschungszentrum

Bochum, 44791, Germany

Location

Universitätsklinikum Ulm; Klinik für Neurologie

Ulm, 89081, Germany

Location

NIHR Welcome Trust Birmingham CRF - University Hospitals Birmingham; Department of Neuropsychiatry

Birmingham, B15 2FG, United Kingdom

Location

Cardiff University School of Medicine; Institute of Psychological Medicine Clinical Neurosciences

Cardiff, CF24 4HQ, United Kingdom

Location

National Hospital For Neurology and Neurosurgery

London, WC1N 3BG, United Kingdom

Location

Central Manchester University Hospitals NHS Foundation Trust; Manchester Centre for Genomic Medicine

Manchester, M13 9WL, United Kingdom

Location

MeSH Terms

Conditions

Huntington Disease

Condition Hierarchy (Ancestors)

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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2018
• First Posted: September 11, 2018
• Study Start: December 5, 2018
• Primary Completion: May 7, 2021
• Study Completion: May 7, 2022
• Last Updated: January 3, 2025
• Results First Posted: January 3, 2025

Record last verified: 2024-11

Locations

US (6); DE (3); GB (4); CA (2)