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

NCT ID: NCT05686551

Last Updated: 2025-11-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

301 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-02-03

Study Completion Date

2027-04-01

Brief Summary

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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).

Detailed Description

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Conditions

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Huntington Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Tominersen 60 milligrams (mg)

Group Type EXPERIMENTAL

Tominersen 60 mg

Intervention Type DRUG

60 mg tominersen administered intrathecally every 16 weeks (Q16W).

Placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Matching placebo administered intrathecally Q16W.

Tominersen 100 mg

Group Type EXPERIMENTAL

Tominersen 100 mg

Intervention Type DRUG

100 mg tominersen administered intrathecally Q16W.

Interventions

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Tominersen 60 mg

60 mg tominersen administered intrathecally every 16 weeks (Q16W).

Intervention Type DRUG

Placebo

Matching placebo administered intrathecally Q16W.

Intervention Type DRUG

Tominersen 100 mg

100 mg tominersen administered intrathecally Q16W.

Intervention Type DRUG

Other Intervention Names

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RO7234292; RG6042 RO7234292; RG6042

Eligibility Criteria

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Inclusion Criteria

-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/m2)
* Study companion

Exclusion Criteria

* Current or previous use of an antisense oligonucleotide (ASO) (including small interfering ribonucleic acid \[RNA\]) or any huntingtin gene/protein (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
Minimum Eligible Age

25 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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Uab Medicine

Birmingham, Alabama, United States

Site Status

Barrow Neurological Institute

Phoenix, Arizona, United States

Site Status

University of California Davis Medical System

Sacramento, California, United States

Site Status

CenExel Rocky Mountain Clinical Research, LLC

Englewood, Colorado, United States

Site Status

Georgetown University

Washington D.C., District of Columbia, United States

Site Status

University of Florida

Gainesville, Florida, United States

Site Status

University of South Florida

Tampa, Florida, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Site Status

John Hopkins University School of Medicine

Baltimore, Maryland, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

Dent Neurological Institute

Amherst, New York, United States

Site Status

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

The University of Texas Health Science Center at Houston

Houston, Texas, United States

Site Status

EvergreenHealth Investigational Drug Services

Kirkland, Washington, United States

Site Status

Inland Northwest Research

Spokane, Washington, United States

Site Status

CINME

Buenos Aires, , Argentina

Site Status

Hospital Ramos Mejía

CABA, , Argentina

Site Status

INEBA

Capital Federal, , Argentina

Site Status

Hospital Britanico de Buenos Aires

Ciudad Autonoma Buenos Aires, , Argentina

Site Status

Monash Medical Centre

Clayton, Victoria, Australia

Site Status

Royal Melbourne Hospital

Parkville, Victoria, Australia

Site Status

Perron Institute for Neurological and Translational Science

Nedlands, Western Australia, Australia

Site Status

Uniklinik fuer Neurologie, Medizinische Universitaet Innsbruck

Innsbruck, , Austria

Site Status

University of Alberta Hospital

Edmonton, Alberta, Canada

Site Status

Montreal Neurological Inst

Montreal, Quebec, Canada

Site Status

Rigshospitalet, Hukommelsesklinikken

København Ø, , Denmark

Site Status

CHU Angers, Batiement Larrey 2, Neurologie

Angers, , France

Site Status

Groupe Hospitalier Pellegrin

Bordeaux, , France

Site Status

Hopital Henri Mondor

Créteil, , France

Site Status

Hopital Roger Salengro Service de Neurologie

Lille, , France

Site Status

CHU de la Timone - Hopital d Adultes

Marseille, , France

Site Status

Hopital Gui de Chauliac

Montpellier, , France

Site Status

CHU Strasbourg Hpital Hautepierre

Strasbourg, , France

Site Status

CHU toulouse - Hôpital Purpan

Toulouse, , France

Site Status

Uniklinik RWTH Aachen

Aachen, , Germany

Site Status

Charité - Universitätsmed. Berlin, Klinik für Psychiatrie und Psychotherapie

Berlin, , Germany

Site Status

St. Josef-Hospital, Neurologische Klinik der Ruhr-Uni

Bochum, , Germany

Site Status

German Center for Neurodegenerative Diseases (DZNE)

Bonn, , Germany

Site Status

Universitätsklinikum Erlangen, Abteilung Molekulare Neurologie

Erlangen, , Germany

Site Status

Universitätsklinikum Schleswig-Holstein / Campus Lübeck

Lübeck, , Germany

Site Status

kbo - Isar-Amper-Klinikum Taufkirchen

Taufkirchen, , Germany

Site Status

Universitätsklinikum Ulm

Ulm, , Germany

Site Status

Ospedale Bellaria

Bologna, Emilia-Romagna, Italy

Site Status

Azienda Ospedaliera Sant'Andrea

Rome, Lazio, Italy

Site Status

Fondazione IRCCS Istituto Neurologico Carlo Besta

Milan, Lombardy, Italy

Site Status

New Zealand Brain Research Institute

Christchurch, , New Zealand

Site Status

Waikato Hospital

Hamilton, , New Zealand

Site Status

Szpital Sw. Wojciecha

Gdansk, , Poland

Site Status

Krakowska Akademia Neurologii Sp z o.o. Centrum Neurologii K

Krakow, , Poland

Site Status

Wojskowy Instytut Medycyny Lotniczej

Warsaw, , Poland

Site Status

Hospital de Santa Maria

Lisbon, , Portugal

Site Status

CNS - Campus Neurológico

Torres Vedras, , Portugal

Site Status

Hospital de Cruces

Barakaldo, Vizcaya, Spain

Site Status

Hospital Universitario de Badajoz

Badajoz, , Spain

Site Status

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Site Status

Hospital Universitario de Burgos. Servicio de Neurología

Burgos, , Spain

Site Status

Hospital Ramon y Cajal

Madrid, , Spain

Site Status

Hospital Universitario Virgen Macarena

Seville, , Spain

Site Status

Hospital Universitario la Fe

Valencia, , Spain

Site Status

Universitätsspital Basel

Basel, , Switzerland

Site Status

Neurozentrum Siloah

Gümligen, , Switzerland

Site Status

University Hospitals Birmingham NHS Foundation Trust

Birmingham, , United Kingdom

Site Status

Addenbrookes Hospital

Cambridge, , United Kingdom

Site Status

Chapel Allerton Hospital

Leeds, , United Kingdom

Site Status

UCL Hospital NHS Trust

London, , United Kingdom

Site Status

John Radcliffe Hospital

Oxford, , United Kingdom

Site Status

Southampton University Hospitals NHS Trust

Southampton, , United Kingdom

Site Status

Countries

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United States Argentina Australia Austria Canada Denmark France Germany Italy New Zealand Poland Portugal Spain Switzerland United Kingdom

References

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McColgan P, Thobhani A, Boak L, Schobel SA, Nicotra A, Palermo G, Trundell D, Zhou J, Schlegel V, Sanwald Ducray P, Hawellek DJ, Dorn J, Simillion C, Lindemann M, Wheelock V, Durr A, Anderson KE, Long JD, Wild EJ, Landwehrmeyer GB, Leavitt BR, Tabrizi SJ, Doody R; GENERATION HD1 Investigators. Tominersen in Adults with Manifest Huntington's Disease. N Engl J Med. 2023 Dec 7;389(23):2203-2205. doi: 10.1056/NEJMc2300400. No abstract available.

Reference Type DERIVED
PMID: 38055260 (View on PubMed)

Other Identifiers

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Other

Identifier Type: OTHER

Identifier Source: secondary_id

2022-001991-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2023-503928-10-00

Identifier Type: CTIS

Identifier Source: secondary_id

BN42489

Identifier Type: -

Identifier Source: org_study_id

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