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

Roche

Status and phase

Completed

Phase 1

Conditions

Huntington's Disease

Treatments

Other: No Study Drug was Administered in this Study

Study type

Interventional

Funder types

Industry

Identifiers

NCT03664804

BN40422

Details and patient eligibility

About

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).

Enrollment

95 patients

Sex

All

Ages

25 to 65 years old

Volunteers

No Healthy Volunteers

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