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

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

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03664804

Enrollment

Registered

2018-09-11

Start date

2018-12-05

Completion date

2022-05-07

Last updated

2025-01-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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).

Interventions

OTHERNo Study Drug was Administered in this Study

No study drug was administered in this study

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

OTHER

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

25 Years to 65 Years

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

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline in Biomarkers of Neuronal Injury (CSF NfL and Tau) at 3, 9, and 15 Months	Baseline to 15 Months	The reported date appreciations are as follows: CSF = Cerebrospinal Fluid; NfL = Neurofilament Light Chain. An overview of percentage change from baseline in geometric means for CSF tau and CSF NfL, and CSF YKL-40 are reported
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	Baseline to 15 Months	Data for Least Square (LS) mean percentage change from baseline to Months 3, 9, and 15 for ventricular volume, caudate volume, and whole brain volume, based on boundary shift integrals (BSIs) are reported
Change From Baseline in the Following Clinical Endpoints at 3, 9, and 15 Months: cUHDRS, TFC, TMS, SDMT, SWR Test and IS	Baseline to 15 Months	The reported data are as follows: 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. cUHDRS: score range from -3.06 (worst) to not defined maximum (best); Stroop Word Reading Test: score range not defined, higher scores indicate better cognitive performance; Symbol Digit Modalities Test: score range from 0 (worst) to 110 (best); Total Functional Capacity: score range from 0 (worst) to 13 (best); Total Motor Scale: score range from 0 (best) to 124 (worst). Data at Month 3, 9, and 15 are reported respectively

Secondary

Measure	Time frame	Description
Within-Participant Change From Baseline in CSF mHTT Levels at 3, 9, and 15 Months	Baseline to 15 Months	mHTT=Mutant Huntingtin Protein. New stability information has revealed that all samples for this outcome measure were out of stability, leaving no valid data points. Therefore there is no data to report.
Association of Change From Baseline in Brain Atrophy Endpoints, as Determined by Brain MRI	Baseline to 15 Months	New stability information has revealed that all samples for this outcome measure were out of stability, leaving no valid data points. Therefore there is no data to report.
Association of Change From Baseline in Cerebrospinal Fluid (FSF) mHTT With Change From Baseline in Clinical Measure	Baseline to 15 Months	New stability information has revealed that all samples for this outcome measure were out of stability, leaving no valid data points. Therefore there is no data to report.
Association of Change From Baseline in Biomarkers of Neuronal Injury	Baseline to 15 Months	New stability information has revealed that all samples for this outcome measure were out of stability, leaving no valid data points. Therefore there is no data to report.

Countries

Canada, Germany, United Kingdom, United States

Participant flow

Recruitment details

A total of 93 patients (97.9%) were included in the safety population and the intent-to-treat (ITT) population. Two patients were excluded from both the analysis populations as the patients had discontinued the study.

Pre-assignment details

Out of 95 participants recruited, 2 were withdrawn before the study intervention.

Participants by arm

Arm	Count
Participants With Early Manifest Stage I or II Huntington's Disease (HD) No study drug was administered in this study	95
Total	95

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Withdrawal by Subject	7

Baseline characteristics

Characteristic	Participants With Early Manifest Stage I or II Huntington's Disease (HD)
Age, Continuous	48.1 Years STANDARD_DEVIATION 9.9
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	92 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	1 Participants
Race (NIH/OMB) Black or African American	1 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants
Race (NIH/OMB) White	89 Participants
Sex: Female, Male Female	36 Participants
Sex: Female, Male Male	59 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	29 / 93
other Total, other adverse events	29 / 93
serious Total, serious adverse events	0 / 93

Outcome results

Primary

Change From Baseline in Biomarkers of Neuronal Injury (CSF NfL and Tau) at 3, 9, and 15 Months

The reported date appreciations are as follows: CSF = Cerebrospinal Fluid; NfL = Neurofilament Light Chain. An overview of percentage change from baseline in geometric means for CSF tau and CSF NfL, and CSF YKL-40 are reported