Clinical trial NCT03664804: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Huntington's Disease
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2018-09-11
Enrollment: 95
Sex: ALL
Minimum age (years): 25
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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).


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

Primary outcomes:
measure: Change From Baseline in the Following Clinical Endpoints at 3, 9, and 15 Months: cUHDRS, TFC, TMS, SDMT, SWR Test and IS
timeFrame: Baseline to 15 Months
measure: Change From Baseline in Biomarkers of Neuronal Injury (CSF NfL and Tau) at 3, 9, and 15 Months
timeFrame: Baseline to 15 Months
measure: 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
timeFrame: Baseline to 15 Months
Secondary outcomes:
measure: Within-Participant Change From Baseline in CSF mHTT Levels at 3, 9, and 15 Months
timeFrame: Baseline to 15 Months
measure: Association of Change From Baseline in Cerebrospinal Fluid (FSF) mHTT With Change From Baseline in Clinical Measure
timeFrame: Baseline to 15 Months
measure: Association of Change From Baseline in Biomarkers of Neuronal Injury
timeFrame: Baseline to 15 Months
measure: Association of Change From Baseline in Brain Atrophy Endpoints, as Determined by Brain MRI
timeFrame: Baseline to 15 Months
Other outcomes:
Locations:
city: Englewood
country: United States
facility: CenExel Rocky Mountain Clinical Research, LLC
state: Colorado
city: Washington
country: United States
facility: Georgetown University; Research Division, Psychiatry
state: District of Columbia
city: Wichita
country: United States
facility: Hereditary Neurological Disease Centre (HNDC)
state: Kansas
city: Baltimore
country: United States
facility: John Hopkins University School of Medicine
state: Maryland
city: New York
country: United States
facility: Columbia University
state: New York
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston; McGovern Medical School
state: Texas
city: Vancouver
country: Canada
facility: The University of British Columbia; The Centre for Huntington Disease
state: British Columbia
city: Markham
country: Canada
facility: Centre for Movement Disorders (Neuropharm Consulting Inc.)
state: Ontario
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin, Campus Charité Mitte; Klinik für Psychiatrie und Psychotherapi
city: Bochum
country: Germany
facility: St. Josef and St. Elisabeth gGmbH ; St. Josef Hospital Bochum; Neurologisches Forschungszentrum
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm; Klinik für Neurologie
city: Birmingham
country: United Kingdom
facility: NIHR Welcome Trust Birmingham CRF - University Hospitals Birmingham; Department of Neuropsychiatry
city: Cardiff
country: United Kingdom
facility: Cardiff University School of Medicine; Institute of Psychological Medicine Clinical Neurosciences
city: London
country: United Kingdom
facility: National Hospital For Neurology and Neurosurgery
city: Manchester
country: United Kingdom
facility: Central Manchester University Hospitals NHS Foundation Trust; Manchester Centre for Genomic Medicine
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: