Huntington's DiseasePhase 1NCT03664804

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

A Phase 1 study testing No Study Drug was Administered in this Study in people with Huntington's Disease, run by Hoffmann-La Roche at 15 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

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). Read more about this study

Who is it for?: Ages 25 to 65 years
Conditions the study is for: Huntington's Disease
What is being tested?: No Study Drug was Administered in this Study
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 95 participants
Where: 15 sitesin 4 countries
Study dates: 5 Dec 2018to 7 May 2022
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 25 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Show all 11Show fewer

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

Who cannot join

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

Show all 17Show fewer

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

Trial locations and contacts

15 sites in 4 countries.

Country

City, postcode or hospital

15 sites in 4 countries

United States6 sites

John Hopkins University School of Medicine
Baltimore, Maryland, 21287
CenExel Rocky Mountain Clinical Research, LLC
Englewood, Colorado, 80113
The University of Texas Health Science Center at Houston; McGovern Medical School
Houston, Texas, 77030
Columbia University
New York, New York, 10032-3725
Georgetown University; Research Division, Psychiatry
Washington D.C., District of Columbia, 20007
Hereditary Neurological Disease Centre (HNDC)
Wichita, Kansas, 67226

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United Kingdom4 sites

NIHR Welcome Trust Birmingham CRF - University Hospitals Birmingham; Department of Neuropsychiatry
Birmingham, B15 2FG
Cardiff University School of Medicine; Institute of Psychological Medicine Clinical Neurosciences
Cardiff, CF24 4HQ
National Hospital For Neurology and Neurosurgery
London, WC1N 3BG
Central Manchester University Hospitals NHS Foundation Trust; Manchester Centre for Genomic Medicine
Manchester, M13 9WL

Other trials in United Kingdom

Germany3 sites

Charité - Universitätsmedizin Berlin, Campus Charité Mitte; Klinik für Psychiatrie und Psychotherapi
Berlin, 10117
St. Josef and St. Elisabeth gGmbH ; St. Josef Hospital Bochum; Neurologisches Forschungszentrum
Bochum, 44791
Universitätsklinikum Ulm; Klinik für Neurologie
Ulm, 89081

Other trials in Germany

Canada2 sites

Centre for Movement Disorders (Neuropharm Consulting Inc.)
Markham, Ontario, L6B 1C9
The University of British Columbia; The Centre for Huntington Disease
Vancouver, British Columbia, V6T 2B5

Other trials in Canada

About this study

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

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).

Conditions: Huntington's Disease
Being tested: No Study Drug was Administered in this Study
Medical subject headings: Huntington Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

No Study Drug was Administered in this StudyOther
No study drug was administered in this study

Study groups in NCT03664804
Study group	Role	What they receive
Participants with Early Manifest Stage I or II HD	Other	No study drug was administered in this study Receives: Other: No Study Drug was Administered in this Study

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline in the Following Clinical Endpoints at 3, 9, and 15 Months: cUHDRS, TFC, TMS, SDMT, SWR Test and IS
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
Measured: Baseline to 15 Months
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
Measured: Baseline to 15 Months
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
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
Measured: Baseline to 15 Months

Secondary outcomes (4)

Within-Participant Change From Baseline in CSF mHTT Levels at 3, 9, and 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.
Measured: Baseline to 15 Months
Association of Change From Baseline in Cerebrospinal Fluid (FSF) mHTT With Change From Baseline in Clinical Measure
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.
Measured: Baseline to 15 Months
Association of Change From Baseline in Biomarkers of Neuronal Injury
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.
Measured: Baseline to 15 Months
Association of Change From Baseline in Brain Atrophy Endpoints, as Determined by Brain MRI
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.
Measured: Baseline to 15 Months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

5 Dec 20187 May 2022

First posted11 Sep 2018
Study start5 Dec 2018
Primary completion7 May 2021
Study completion7 May 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Huntington's DiseaseStudies of the same condition, open and under way.
More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Other
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 95 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03664804
Sponsor's protocol ID: BN40422
Status last verified: Nov 2024
First submitted: 7 Sep 2018
Last updated: 3 Jan 2025
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: No
FDA-regulated device: No

Publications

Lugrin C, Alecci L, Simillion C, Volkova-Volkmar E, Giboin LS, Kinsella FC, McColgan P, Wild EJ, Dorn J. Longitudinal assessment of chorea in Huntington's disease using digital passive monitoring. NPJ Digit Med. 2026 Apr 25;9(1):495. doi: 10.1038/s41746-026-02661-y.
PubMed 42032152

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 3 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multi-Site, Prospective, Longitudinal, Cohort Study Measuring Cerebrospinal Fluid-Mutant Huntingtin Protein in Patients With Huntington's Disease
ClinicalTrials.gov ID: NCT03664804
Acronym / sponsor ID: BN40422
Conditions: Huntington's Disease
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 95 participants (actual)
Lead sponsor: Hoffmann-La RocheIndustry (pharma, biotech, devices)
Study start: 5 Dec 2018 (actual)
Primary completion: 7 May 2021 (actual)
Study completion: 7 May 2022 (actual)
First posted: 11 Sep 2018 (actual)
Results: Posted 3 Jan 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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).

Study design

Primary purpose: Other
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Participants with Early Manifest Stage I or II HD	Other	Other: No Study Drug was Administered in this StudyNo study drug was administered in this study

Who may qualify

Ages: 25 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (11 listed)

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

Key exclusion criteria (17 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
No Study Drug was Administered in this StudyNo study drug was administered in this study	Other	Participants with Early Manifest Stage I or II HD

Primary outcome

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

4 secondary outcomes

Within-Participant Change From Baseline in CSF mHTT Levels at 3, 9, and 15 Months
Time frame: Baseline to 15 Months
Association of Change From Baseline in Cerebrospinal Fluid (FSF) mHTT With Change From Baseline in Clinical Measure
Time frame: Baseline to 15 Months
Association of Change From Baseline in Biomarkers of Neuronal Injury
Time frame: Baseline to 15 Months
Association of Change From Baseline in Brain Atrophy Endpoints, as Determined by Brain MRI
Time frame: Baseline to 15 Months

Results and safety

Results posted to the registry on 3 Jan 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Participants With Early Manifest Stage I or II Huntington's Disease (HD)	95	88

Primary outcome: 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. Mean (Standard Deviation). Unit: Scores on a scale

Measure	Participants With Early Manifest Stage I or II Huntington's Disease (HD) n = 93
Composite UHDRS (cUHDRS) Month 3	0.19 (1.08)
Composite UHDRS (cUHDRS) Month 9	-0.12 (1.24)
Composite UHDRS (cUHDRS) Month 15	-0.76 (1.49)
UHDRS Total Functional Capacity (TFC) Month 3	-0.24 (0.89)
UHDRS Total Functional Capacity (TFC) Month 9	-0.33 (1.31)
UHDRS Total Functional Capacity (TFC) Month 15	-1.10 (1.60)
UHDRS Total Motor Score (TMS) Month 3	1.38 (5.73)
UHDRS Total Motor Score (TMS) Month 9	2.78 (8.36)

Population analysed: ITT Population

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

Time frame: Baseline to 15 Months. Geometric mean (95% Confidence Interval). Unit: Percent Change

Measure	Participants With Early Manifest Stage I or II Huntington's Disease (HD) n = 93
Tau Month 3	1.759 (-2.927 to 6.671)
Tau Month 9	3.731 (-1.960 to 9.751)
Tau Month 15	10.097 (1.283 to 19.678)
NfL Month 3	-0.052 (-2.614 to 2.578)
NfL Month 9	4.035 (-0.149 to 8.395)
NfL Month 15	5.971 (1.629 to 10.499)
YKL-40 Month 3	-0.763 (-3.268 to 1.806)
YKL-40 Month 9	1.026 (-2.112 to 4.263)

Population analysed: ITT Population

Primary outcome: 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

Time frame: Baseline to 15 Months. Least squares mean (95% Confidence Interval). Unit: Percentage change

Measure	Participants With Early Manifest Stage I or II Huntington's Disease (HD) n = 93
Caudate Volume Month 3	1.345 (0.875 to 1.815)
Caudate Volume Month 9	2.811 (2.285 to 3.337)
Caudate Volume Month 15	4.806 (4.057 to 5.554)
Ventricular Volume Month 3	2.662 (2.016 to 3.308)
Ventricular Volume Month 9	5.124 (4.132 to 6.115)
Ventricular Volume Month 15	9.622 (8.195 to 11.050)
Whole Brain Volume Month 3	0.304 (0.175 to 0.434)
Whole Brain Volume Month 9	0.513 (0.346 to 0.681)

Population analysed: ITT Population

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: AE timeframe: From Baseline to 15 Months. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
NHS Participants With Early Manifest Stage I or II HD	0 of 93 (0%)	29 of 93 (31.2%)	29 of 93

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Jan 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 42032152Lugrin C, Alecci L, Simillion C, Volkova-Volkmar E, Giboin LS, Kinsella FC, McColgan P, Wild EJ, Dorn J. Longitudinal assessment of chorea in Huntington's disease using digital passive monitoring. NPJ Digit Med. 2026 Apr 25;9(1):495. doi: 10.1038/s41746-026-02661-y.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Clinical Trials study director

Hoffmann-La Roche

15 sites in 4 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing No Study Drug was Administered in this Study in people with Huntington's Disease, run by Hoffmann-La Roche at 15 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United States, United Kingdom, Germany, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03664804, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jan 2025.