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

Huntington's Disease Clinical Trial

Official title:

A Multi-Site, Prospective, Longitudinal, Cohort Study Measuring Cerebrospinal Fluid-Mutant Huntingtin Protein in Patients With Huntington's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03664804
• Other study ID #: BN40422
• Status: Completed
• Phase: Phase 1
• Start date: December 5, 2018
• Est. completion date: May 7, 2021

Study information

• Verified date: October 2021
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 95
• Est. completion date: May 7, 2021
• Est. primary completion date: May 7, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Huntington Disease
• Huntington's Disease

Intervention

Other:
• No Study Drug was Administered in this Study
No study drug was administered in this study

Locations

Country	Name	City	State
Canada	Centre for Movement Disorders (Neuropharm Consulting Inc.)	Markham	Ontario
Canada	The University of British Columbia; The Centre for Huntington Disease	Vancouver	British Columbia
Germany	Charité - Universitätsmedizin Berlin, Campus Charité Mitte; Klinik für Psychiatrie und Psychotherapi	Berlin
Germany	St. Josef and St. Elisabeth gGmbH ; St. Josef Hospital Bochum; Neurologisches Forschungszentrum	Bochum
Germany	Universitätsklinikum Ulm; Klinik für Neurologie	Ulm
United Kingdom	NIHR Welcome Trust Birmingham CRF - University Hospitals Birmingham; Department of Neuropsychiatry	Birmingham
United Kingdom	Cardiff University School of Medicine; Institute of Psychological Medicine Clinical Neurosciences	Cardiff
United Kingdom	National Hospital For Neurology and Neurosurgery	London
United Kingdom	Central Manchester University Hospitals NHS Foundation Trust; Manchester Centre for Genomic Medicine	Manchester
United States	John Hopkins University School of Medicine	Baltimore	Maryland
United States	Rocky Mountain Movement Disorders Center	Englewood	Colorado
United States	The University of Texas Health Science Center at Houston; McGovern Medical School	Houston	Texas
United States	Columbia University	New York	New York
United States	Georgetown University; Research Division, Psychiatry	Washington	District of Columbia
United States	Hereditary Neurological Disease Centre (HNDC)	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Canada,  Germany,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline in the Following Clinical Endpoints at 3, 9, and 15 Months: cUHDRS, TFC, TMS, SDMT, SWR Test, and IS	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	Baseline to 15 months
Primary	Change from Baseline in Biomarkers of Neuronal Injury (e.g., CSF NfL and tau) at 3, 9, and 15 Months	CSF = Cerebrospinal Fluid NfL = Neurofilament Light Chain	Baseline to 15 Months
Primary	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		Baseline to 15 Months
Secondary	Within-Participant Change from Baseline in CSF mHTT Levels at 3, 9, and 15 Months	mHTT=Mutant Huntingtin Protein	Baseline to 15 Months
Secondary	Association of Change from Baseline in Clinical Measures (cUHDRS, TFC, TMS, SDMT, SWR, and IS) at 3, 9, and 15 Months		Baseline to 15 Months
Secondary	Association of Change from Baseline in Biomarkers of Neuronal Injury (e.g., CSF NfL and tau) at 3, 9, and 15 Months		Baseline to 15 Months
Secondary	Association of Change from Baseline in Brain Atrophy Endpoints, as Determined by Brain MRI at 3, 9, and 15 Months		Baseline to 15 Months