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.

Phase 2

Active, not recruiting

• Conditions: Huntington Disease
• Interventions: Drug: Placebo; Drug: Tominersen 60 mg; Drug: Tominersen 100 mg

• Registration Number: NCT05686551
• Lead Sponsor: Hoffmann-La Roche

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-12-16
• Study First Submitted QC: 2023-01-06
• Study First Posted: 2023-01-17
• Study Start: 2023-02-03
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-03
• Last Update Posted: 2025-03-05
• Primary Completion: 2026-02-28
• Study Completion: 2027-04-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 301

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
Tominersen 60 mg	Tominersen 60 mg	-
Tominersen 100 mg	Tominersen 100 mg	-

Primary Outcome Measures

Name	Time	Method
Change from baseline in clinical laboratory results - Cerebrospinal fluid (CSF) White Blood Cell (WBC) (1/uL)	From Baseline Visit (Day 1), and Months 4, 8, 9, 12, 16
Change in baseline in structural MRI assessing any new abnormalities including radiographic features consistent with hydrocephalus and other relevant MRI safety findings	From Baseline, Months 4, 8, 12, 16 and Up to Approximately Month 24
Incidence and severity of adverse events, with severity determined according to the Adverse Event Severity Grading Scale	Up to Approximately 24 Months
Change from baseline in clinical laboratory results Cerebrospinal fluid (CSF) protein (g/L)	From Baseline Visit (Day 1), and Months 4, 8, 9, 12, 16
Percentage change from baseline in geometric means of CSF mHTT protein levels at Month 9	Baseline and Month 9
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
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

Secondary Outcome Measures

Name	Time	Method
Change from baseline in MoCA Scores	From Baseline, Months 4, 8, 12, 16 and up to approximately Month 24
Percentage of participants with suicidal ideation or behavior as assessed by C-SSRS score at each visit, including detailed focus on any individual cases identified as having severe ideation or behavior during the study conduct	Up to Approximately 24 Months
Change from baseline at 16 months for the assessments of TFC (non-U.S. sites) Scores	Baseline to 16 Months
Change from baseline at 16 months for the assessments of cUHDRS (U.S. sites) Scores	Baseline to 16 Months
Change from baseline at 16 months for the assessments of Symbol Digit Modalities Test (SDMT) Scores	Baseline to 16 Months
Change from Baseline at 16 Months for the Assessments of Stroop Word Reading (SWR) Scores	Baseline to 16 Months
Change from baseline at 16 months for the assessments of Total Motor Score (TMS)	Baseline to 16 Months
Change from baseline in CSF Neurofilament light Chain (NfL) levels at 16 months	Baseline to 16 Months
Incidence of anti-drug antibodies (ADAs) at specified timepoints relative to the prevalence of ADAs at baseline	From Baseline, Months 4, 8, 12, 16 and Up to Approximately Month 24
Titers determined if ADAs are identified	From Baseline, Months 4, 8, 12, 16 and Up to Approximately Month 24

Trial Locations

Locations (72)

Uab Medicine; 🇺🇸 Birmingham, Alabama, United States

Barrow Neurological Institute; 🇺🇸 Phoenix, Arizona, United States

University of California Davis Medical System; 🇺🇸 Sacramento, California, United States

CenExel Rocky Mountain Clinical Research, LLC; 🇺🇸 Englewood, Colorado, United States

Georgetown University; 🇺🇸 Washington, District of Columbia, United States

University of Florida; 🇺🇸 Gainesville, Florida, United States

University of South Florida; 🇺🇸 Tampa, Florida, United States

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

German Center for Neurodegenerative Diseases (DZNE); 🇩🇪 Bonn, Germany

Universitätsklinikum Erlangen, Abteilung Molekulare Neurologie; 🇩🇪 Erlangen, Germany

Universitätsklinikum Schleswig-Holstein / Campus Lübeck; 🇩🇪 Lübeck, Germany

kbo - Isar-Amper-Klinikum Taufkirchen; 🇩🇪 Taufkirchen, Germany

Universitätsklinikum Ulm; 🇩🇪 Ulm, Germany

Ospedale Bellaria; 🇮🇹 Bologna, Emilia-Romagna, Italy

Azienda Ospedaliera Sant'Andrea; 🇮🇹 Roma, Lazio, Italy

Fondazione IRCCS Istituto Neurologico Carlo Besta; 🇮🇹 Milano, Lombardia, Italy

New Zealand Brain Research Institute; 🇳🇿 Christchurch, New Zealand

Waikato Hospital; 🇳🇿 Hamilton, New Zealand

Szpital Sw. Wojciecha; 🇵🇱 Gda?sk, Poland

Krakowska Akademia Neurologii Sp z o.o. Centrum Neurologii K; 🇵🇱 Krakow, Poland

Wojskowy Instytut Medycyny Lotniczej; 🇵🇱 Warszawa, Poland

Instytut Psychiatrii i Neurologii; 🇵🇱 Warszawa, Poland

Hospital de Santa Maria; 🇵🇹 Lisboa, Portugal

CNS - Campus Neurológico; 🇵🇹 Torres Vedras, Portugal

Hospital de Cruces; 🇪🇸 Barakaldo, Vizcaya, Spain

Hospital Universitario de Badajoz; 🇪🇸 Badajoz, Spain

Hospital de la Santa Creu i Sant Pau; 🇪🇸 Barcelona, Spain

Hospital Universitario de Burgos. Servicio de Neurología; 🇪🇸 Burgos, Spain

Hospital Ramon y Cajal; 🇪🇸 Madrid, Spain

Hospital Universitario Virgen Macarena; 🇪🇸 Sevilla, Spain

Hospital Universitario la Fe; 🇪🇸 Valencia, Spain

Universitätsspital Basel; 🇨🇭 Basel, Switzerland

Neurozentrum Siloah; 🇨🇭 Gümligen, Switzerland

University Hospitals Birmingham NHS Foundation Trust; 🇬🇧 Birmingham, United Kingdom

Addenbrookes Hospital; 🇬🇧 Cambridge, United Kingdom

Chapel Allerton Hospital; 🇬🇧 Leeds, United Kingdom

UCL Hospital NHS Trust; 🇬🇧 London, United Kingdom

John Radcliffe Hospital; 🇬🇧 Oxford, United Kingdom

Southampton University Hospitals NHS Trust; 🇬🇧 Southampton, United Kingdom

CHU Angers, Batiement Larrey 2, Neurologie; 🇫🇷 Angers Cedex 9, France

Groupe Hospitalier Pellegrin; 🇫🇷 Bordeaux, France

Hopital Henri Mondor; 🇫🇷 Creteil, 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 Hôpital Hautepierre; 🇫🇷 Strasbourg, France

CHU toulouse - Hôpital Purpan; 🇫🇷 Toulouse, France

Northwestern University; 🇺🇸 Chicago, Illinois, United States

University of Iowa Hospitals and Clinics; 🇺🇸 Iowa City, Iowa, United States

John Hopkins University School of Medicine; 🇺🇸 Baltimore, Maryland, United States

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States

Henry Ford Hospital; 🇺🇸 Detroit, Michigan, United States

Dent Neurological Institute; 🇺🇸 Amherst, New York, United States

University of Pittsburgh; 🇺🇸 Pittsburgh, Pennsylvania, United States

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States

The University of Texas Health Science Center at Houston; 🇺🇸 Houston, Texas, United States

EvergreenHealth Investigational Drug Services; 🇺🇸 Kirkland, Washington, United States

Inland Northwest Research; 🇺🇸 Spokane, Washington, United States

CINME; 🇦🇷 Buenos Aires, Argentina

Hospital Ramos Mejía; 🇦🇷 Caba, Argentina

INEBA; 🇦🇷 Capital Federal, Argentina

Hospital Britanico de Buenos Aires; 🇦🇷 Ciudad Autonoma Buenos Aires, Argentina

Westmead Hospital; 🇦🇺 Westmead, New South Wales, Australia

Monash Medical Centre; 🇦🇺 Clayton, Victoria, Australia

Royal Melbourne Hospital; 🇦🇺 Parkville, Victoria, Australia

Perron Institute for Neurological and Translational Science; 🇦🇺 Nedlands, Western Australia, Australia

Uniklinik fuer Neurologie, Medizinische Universitaet Innsbruck; 🇦🇹 Innsbruck, Austria

University of Alberta Hospital; 🇨🇦 Edmonton, Alberta, Canada

Montreal Neurological Inst; 🇨🇦 Montreal, Quebec, Canada

Rigshospitalet, Hukommelsesklinikken; 🇩🇰 København Ø, Denmark