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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03664804
Recruitment Status : Completed
First Posted : September 11, 2018
Last Update Posted : October 27, 2021
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE September 7, 2018
First Posted Date  ICMJE September 11, 2018
Last Update Posted Date October 27, 2021
Actual Study Start Date  ICMJE December 5, 2018
Actual Primary Completion Date May 7, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE
 (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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Measure Cerebrospinal Fluid Mutant Huntingtin Protein in Participants With Early Manifest Stage I or Stage II Huntington's Disease
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE Huntington's Disease
Intervention  ICMJE Other: No Study Drug was Administered in this Study
No study drug was administered in this study
Study Arms  ICMJE 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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 12, 2021)
95
Original Estimated Enrollment  ICMJE
 (submitted: September 7, 2018)
100
Actual Study Completion Date  ICMJE May 7, 2021
Actual Primary Completion Date May 7, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 25 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Germany,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03664804
Other Study ID Numbers  ICMJE 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  ICMJE Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date October 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP