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

• ClinicalTrials.gov Identifier: NCT03664804
• Recruitment Status: Completed
• First Posted: September 11, 2018
• Last Update Posted: October 27, 2021
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: September 7, 2018
• First Posted Date: September 11, 2018
• Last Update Posted Date: October 27, 2021
• Actual Study Start Date: December 5, 2018
• Actual Primary Completion Date: May 7, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 24, 2021)

• Change from Baseline in the Following Clinical Endpoints at 3, 9, and 15 Months: cUHDRS, TFC, TMS, SDMT, SWR Test, and IS [ Time Frame: Baseline to 15 months ]
  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
• Change from Baseline in Biomarkers of Neuronal Injury (e.g., CSF NfL and tau) at 3, 9, and 15 Months [ Time Frame: Baseline to 15 Months ]
  CSF = Cerebrospinal Fluid NfL = Neurofilament Light Chain
• 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 [ Time Frame: Baseline to 15 Months ]

Original Primary Outcome Measures (submitted: September 7, 2018)

• Change from Baseline in the Following Clinical Endpoints at 3, 9, and 15 Months: cUHDRS, TFC, TMS, SDMT, SWR Test, and IS [ Time Frame: Baseline to 15 Months ]
  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
• Change from Baseline in Biomarkers of Neuronal Injury (e.g., CSF NfL and tau) at 3, 9, and 15 Months [ Time Frame: Baseline to 15 Months ]
  CSF = Cerebrospinal Fluid NfL = Neurofilament Light Chain
• 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 [ Time Frame: Baseline to 15 Months ]

Current Secondary Outcome Measures (submitted: September 7, 2018)

• Within-Participant Change from Baseline in CSF mHTT Levels at 3, 9, and 15 Months [ Time Frame: Baseline to 15 Months ]
  mHTT=Mutant Huntingtin Protein
• Association of Change from Baseline in Clinical Measures (cUHDRS, TFC, TMS, SDMT, SWR, and IS) at 3, 9, and 15 Months [ Time Frame: 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 [ Time Frame: Baseline to 15 Months ]
• Association of Change from Baseline in Brain Atrophy Endpoints, as Determined by Brain MRI at 3, 9, and 15 Months [ Time Frame: Baseline to 15 Months ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Measure Cerebrospinal Fluid Mutant Huntingtin Protein in Participants With Early Manifest Stage I or Stage II Huntington's Disease
• Official Title: A Multi-Site, Prospective, Longitudinal, Cohort Study Measuring Cerebrospinal Fluid-Mutant Huntingtin Protein in Patients With Huntington's Disease
• 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Other
• Condition: Huntington's Disease

Intervention

Other: No Study Drug was Administered in this Study

No study drug was administered in this study

Study Arms

Participants with Early Manifest Stage I or II HD

No study drug was administered in this study

Intervention: Other: No Study Drug was Administered in this Study

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 12, 2021): 95
• Original Estimated Enrollment (submitted: September 7, 2018): 100
• Actual Study Completion Date: May 7, 2021
• Actual Primary Completion Date: May 7, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 25 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, Germany, United Kingdom, United States

Administrative Information

• NCT Number: NCT03664804
• Other Study ID Numbers: BN40422
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Same as current
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: October 2021