GENERATION HD2. A Study to Evaluate the Safety, Biomarkers, and Efficacy of Tominersen Compared With Placebo in Participants With Prodromal and Early Manifest Huntington's Disease

NCT05686551 · tracked via the Priya Life Science UK tracker

Sponsor

Hoffmann-La Roche

Phase

Phase 2

Started

2023-02-03

Last updated

2026-08-10

Condition(s) studied

Huntington Disease

Investigational drug(s) / intervention(s)

TominersenPlacebo

Tominersen: Tominersen will be administered at the dose and schedule specified in the protocol.

Placebo: Matching placebo administered IT, Q16W during the DB period.

Study summary

This study will evaluate the safety, biomarkers, and efficacy of tominersen compared with placebo in participants with prodromal and early manifest Huntington's Disease (HD).

Eligibility

Sex

ALL

Min age

25 Years

Max age

50 Years

Healthy volunteers

Inclusion Criteria: DB Period: * HD gene expansion mutation carrier status with a cytosine-adenine-guanine-age product (CAP) score of 400-500 inclusive * Either: * Prodromal HD (defined as Diagnostic Confidence Level (DCL) 2 to 3, Independence Scale (IS) ≥70, and TFC ≥8); Or * Early manifest HD (defined as DCL 4, IS ≥70, and TFC ≥8) * Total body weight \> 40 kilograms (kg) and a body mass index (BMI) within the range of 18-32 kilograms per meter square (kg/m\^2) * Study companion OLE Period: * Participants must have completed the DB treatment period * Participants must remain in the DB Safety follow-up period until OLE period starts Exclusion Criteria: DB Period: * Current or previous use of an antisense oligonucleotide (ASO) (including small interfering ribonucleic acid \[RNA\]) or any HTT lowering therapy (including tominersen) * Anti-platelet or anticoagulant therapy within 14 days prior to screening or anticipated use during the study, including, but not limited to, aspirin (unless ≤ 81 milligrams per day \[mg/day\]), clopidogrel, dipyridamole, warfarin, dabigatran, rivaroxaban, apixaban, and heparin * History of gene therapy, cell transplantation, or brain surgery * Hydrocephalus * Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 5 months after the final dose of study drug * 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 OLE Period: * Early discontinuation from the DB treatment and the safety follow-up (SFU) periods * Pregnant or breastfeeding, or with the intention of becoming pregnant during the study or within the timeframe in which contraception is required * Current or previous use of an ASO other than tominersen (including small interfering RNA) or any other HTT-lowering therapy * Hydrocephalus * Received any active investigational treatment other than tominersen during or since completion of the DB treatment period Key inclusions/exclusion criteria are listed here. Other protocol-defined I/E criteria may apply.

Primary outcome measure(s)

DB Period: Incidence and Severity of Adverse Events (AEs), With Severity Determined According to the AE Severity Grading Scale — Up to approximately 36 months
DB Period: Change From Baseline in Clinical Laboratory Results - Cerebrospinal Fluid (CSF) White Blood Cell (WBC) — Baseline visit (Day 1), and Months 4, 8, 9, 12, 16
DB Period: Change From Baseline in Clinical Laboratory Results - CSF Protein — Baseline visit (Day 1), and Months 4, 8, 9, 12, 16
DB Period: Change From Baseline in Structural Magnetic Resonance Imaging (MRI) Assessing Any New Abnormalities Including Radiographic Features Consistent With Hydrocephalus and Other Relevant MRI Safety Findings — Baseline, Months 4, 8, 12, 16 and up to approximately 36 months
DB Period: Percentage Change From Baseline in Geometric Means of CSF Mutant Huntingtin (mHTT) Protein Levels at Month 9 — Baseline, Month 9
DB Period: Change From Baseline in Composite Unified Huntington's Disease Rating Scale (cUHDRS) Scores (non-U.S. Sites) at 16 Months — Baseline to 16 months
Change in scores on the scale.
DB Period: Change From Baseline in Total Functional Capacity (TFC) Scores (U.S. Sites) at 16 Months — Baseline to 16 months
Change in scores on the scale.
OLE Period: Incidence and Severity of AEs, With Severity Determined According to the AE Severity Grading Scale — Up to approximately 29 months
OLE Period: Change Over Time in Clinical Laboratory Results - CSF WBC — Up to approximately 24 months
OLE Period: Change Over Time in Clinical Laboratory Results - CSF Protein — Up to approximately 24 months
OLE Period: Change From Baseline in Structural MRI Assessing Any New Abnormalities, Including Radiographic Features Consistent With Hydrocephalus and Other Relevant MRI Safety Findings — Up to approximately 29 months

Trial sites (70)

Facility	City	Region
Uab Medicine	Birmingham	Alabama
Barrow Neurological Institute	Phoenix	Arizona
University of California Davis Medical System	Sacramento	California
CenExel Rocky Mountain Clinical Research, LLC	Englewood	Colorado
Georgetown University	Washington D.C.	District of Columbia
University of Florida	Gainesville	Florida
University of South Florida	Tampa	Florida
Northwestern University	Chicago	Illinois
University of Iowa Hospitals and Clinics	Iowa City	Iowa
John Hopkins University School of Medicine	Baltimore	Maryland
Beth Israel Deaconess Medical Center	Boston	Massachusetts
Henry Ford Hospital	Detroit	Michigan
Dent Neurological Institute	Amherst	New York
University of Pittsburgh	Pittsburgh	Pennsylvania
Vanderbilt University Medical Center	Nashville	Tennessee
The University of Texas Health Science Center at Houston	Houston	Texas
EvergreenHealth Investigational Drug Services	Kirkland	Washington
Inland Northwest Research	Spokane	Washington
CINME	Buenos Aires	Argentina
Hospital Ramos Mejía	CABA	Argentina
INEBA	Capital Federal	Argentina
Hospital Britanico de Buenos Aires	Ciudad Autonoma Buenos Aires	Argentina
Monash Medical Centre	Clayton	Victoria
Royal Melbourne Hospital	Parkville	Victoria
Perron Institute for Neurological and Translational Science	Nedlands	Western Australia
Uniklinik fuer Neurologie, Medizinische Universitaet Innsbruck	Innsbruck	Austria
University of Alberta Hospital	Edmonton	Alberta
Montreal Neurological Inst	Montreal	Quebec
Rigshospitalet, Hukommelsesklinikken	København Ø	Denmark
CHU Angers, Batiement Larrey 2, Neurologie	Angers	France
Groupe Hospitalier Pellegrin	Bordeaux	France
Hopital Henri Mondor	Créteil	France
Hopital Roger Salengro Service de Neurologie	Lille	France
CHU de la Timone - Hopital d Adultes	Marseille	France
Hopital Gui de Chauliac	Montpellier	France
CHU Strasbourg Hpital Hautepierre	Strasbourg	France
CHU toulouse - Hôpital Purpan	Toulouse	France
Uniklinik RWTH Aachen	Aachen	Germany
Charité - Universitätsmed. Berlin, Klinik für Psychiatrie und Psychotherapie	Berlin	Germany
St. Josef-Hospital, Neurologische Klinik der Ruhr-Uni	Bochum	Germany

+ 30 more sites — see the full list on the official registry below.

More Hoffmann-La Roche trials in the UK

A Clinical Trial of Trontinemab in Participants With Early Symptomatic Alzheimer's Disease Recruiting

A Gene Delivery Study to Evaluate the Safety and Expression of Delandistrogene Moxeparvovec in Participants Under the Age of Four With Duchenne Muscular Dystrophy (DMD) Active, not recruiting

A Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of RO7268489 as Add-on Therapy to Ocrelizumab, in Participants With Progressive Forms of Multiple Sclerosis (MS) Recruiting

A Study to Evaluate the Efficacy and Safety of Obinutuzumab in Participants With Systemic Lupus Erythematosus Active, not recruiting

A Study Evaluating the Efficacy and Safety of Divarasib Versus Sotorasib or Adagrasib in Participants With Previously Treated KRAS G12C-positive Advanced or Metastatic Non-Small Cell Lung Cancer Active, not recruiting

Other trials for the same condition

A Study to Investigate the Efficacy, Safety and Tolerability of Votoplam in Participants With Huntington's Disease Recruiting

Safety and Efficacy of AMT-130 in European Adults With Early Manifest Huntington's Disease Active, not recruiting

Pridopidine Phase 3 Study in Huntington's Disease Recruiting

An Extension Study to Evaluate the Long-Term Safety and Efficacy of Votoplam in Participants With Huntington's Disease (HD) Active, not recruiting

A Safety and Pharmacokinetics Trial of VO659 in SCA1, SCA3 and HD Recruiting

Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT05686551 on ClinicalTrials.gov ↗ ← All trials in the UK