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.

Huntington Disease Clinical Trial

Official title:

A Phase II, Randomized, Double-Blind, Placebo-Controlled, Dose-Finding Study to Evaluate the Safety, Biomarkers, and Efficacy of Tominersen in Individuals With Prodromal and Early Manifest Huntington's Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05686551
• Other study ID #: BN42489
• Secondary ID: Other
• Status: Recruiting
• Phase: Phase 2
• Start date: February 3, 2023
• Est. completion date: April 1, 2027

Study information

• Verified date: June 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID Number: BN42489 https://forpatients.roche.com
• Phone: 888-662-6728 (U.S. Only)
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: April 1, 2027
• Est. primary completion date: February 28, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years to 50 Years

Eligibility

Key Inclusion Criteria

-Huntington's disease (HD) gene expansion mutation carrier status with a CAP score of 400-500 inclusive

Either:

• Prodromal HD (defined as DCL 2 to 3, Independence Scale (IS) ?70, and ?TFC8); or

• Early manifest HD (defined as DCL 4, Independence Scale (IS) ?70, and ?TFC8);

• Total body weight > 40 kg and a body mass index within the range of 18-32 kg/m2

• Study Companion

Key Exclusion Criteria

• Current or previous use of an ASO (including small interfering 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 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

Related Conditions & MeSH terms

• Huntington Disease

Intervention

Drug:
• Tominersen 60 mg
60 mg tominersen administered intrathecally every 16 weeks
• Placebo
Matching placebo administered intrathecally every 16 weeks
• Tominersen 100 mg
100 mg tominersen administered intrathecally every 16 weeks

Locations

Country	Name	City	State
Argentina	CINME	Buenos Aires
Argentina	Hospital Ramos Mejía	Caba
Argentina	INEBA	Capital Federal
Argentina	Hospital Britanico de Buenos Aires	Ciudad Autonoma Buenos Aires
Australia	Monash Medical Centre	Clayton	Victoria
Australia	Perron Institute for Neurological and Translational Science	Nedlands	Western Australia
Australia	Royal Melbourne Hospital; Department of Neurology	Parkville	Victoria
Australia	WESTMEAD HOSPITAL; Deparment of Neurology	Westmead	New South Wales
Austria	Uniklinik fuer Neurologie, Medizinische Universitaet Innsbruck; Department fuer Neurologie	Innsbruck
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	Centricity Research	Halifax	Nova Scotia
Canada	Montreal Neurological Inst; Clinical Research Unit	Montreal	Quebec
Canada	Health Science Centre	St. John's	Newfoundland and Labrador
Denmark	Rigshospitalet, Hukommelsesklinikken	København Ø
France	CHU Angers, Batiement Larrey 2, Neurologie	Angers Cedex 9
France	Groupe Hospitalier Pellegrin; Service de Neurologie - 3ème étage	Bordeaux
France	Hopital Henri Mondor; Service de Neurologie	Creteil
France	Hopital Roger Salengro Service de Neurologie	Lille
France	CHU de la Timone - Hopital d Adultes; Service de Neurologie	Marseille
France	Hopital Gui de Chauliac; Neurologie	Montpellier
France	CHU Strasbourg Hôpital Hautepierre	Strasbourg
France	CHU toulouse - Hôpital Purpan; Departement de Neurologie	Toulouse
Germany	Uniklinik RWTH Aachen; Klinik für Neurologie	Aachen
Germany	Charité - Universitätsmed. Berlin, Klinik für Psychiatrie und Psychotherapie; Abt. Neuropsychiatrie	Berlin
Germany	St. Josef-Hospital, Neurologische Klinik der Ruhr-Uni; Huntington-Center NRW, Abt. Neurodegeneration	Bochum
Germany	German Center for Neurodegenerative Diseases (DZNE)	Bonn
Germany	Universitätsklinikum Erlangen, Abteilung Molekulare Neurologie	Erlangen
Germany	Universitätsklinikum Schleswig-Holstein / Campus Lübeck; Zentrum für Seltene Erkrankungen	Lübeck
Germany	kbo - Isar-Amper-Klinikum Taufkirchen; kbo - Huntington Zentrum Süd	Taufkirchen
Germany	Universitätsklinikum Ulm; Klinik für Neurologie	Ulm
Italy	Ospedale Bellaria; Istituto delle Scienze Neurologiche	Bologna	Emilia-Romagna
Italy	Fondazione IRCCS Istituto Neurologico Carlo Besta; U.O.C. Genetica Medica-Neurogenetica	Milano	Lombardia
Italy	Azienda Ospedaliera Sant'Andrea; UOC Neurologia	Roma	Lazio
New Zealand	New Zealand Brain Research Institute	Christchurch
New Zealand	Waikato Hospital; Neurology	Hamilton
Poland	Szpital Sw. Wojciecha; Oddzial Neurologiczny	Gda?sk
Poland	Krakowska Akademia Neurologii Sp z o.o. Centrum Neurologii K	Krakow
Poland	Instytut Psychiatrii i Neurologii	Warszawa
Portugal	Hospital de Santa Maria; Servico de Neurologia	Lisboa
Portugal	CNS - Campus Neurológico	Torres Vedras
Spain	Hospital Universitario de Badajoz; Servicio de Neurología	Badajoz
Spain	Hospital de Cruces; Servicio de Neurologia	Barakaldo	Vizcaya
Spain	Hospital de la Santa Creu i Sant Pau; Servicio de Neurologia	Barcelona
Spain	Hospital Universitario de Burgos. Servicio de Neurología	Burgos
Spain	Hospital Ramon y Cajal; Servicio de Neurologia	Madrid
Spain	Hospital Universitario Virgen Macarena; Servicio de Neurologia	Sevilla
Spain	Hospital Universitario la Fe; Servicio de Neurologia	Valencia
Switzerland	Universitätsspital Basel; Neurologie	Basel
Switzerland	Neurozentrum Siloah	Gümligen
United Kingdom	University Hospitals Birmingham NHS Foundation Trust	Birmingham
United Kingdom	Addenbrookes Hospital	Cambridge
United Kingdom	John Radcliffe Hospital; Neurosciences	Chinnor
United Kingdom	Chapel Allerton Hospital; Clinical Genetics	Leeds
United Kingdom	UCL Hospital NHS Trust	London
United Kingdom	Southampton University Hospitals NHS Trust	Southampton
United States	Dent Neurological Institute	Amherst	New York
United States	John Hopkins University School of Medicine	Baltimore	Maryland
United States	Uab Medicine	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Northwestern University	Chicago	Illinois
United States	CenExel Rocky Mountain Clinical Research, LLC	Englewood	Colorado
United States	University of Florida	Gainesville	Florida
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Evergreen Health Care Center	Kirkland	Washington
United States	University of California San Diego	La Jolla	California
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Barrow Neurological Institute	Phoenix	Arizona
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	University of California Davis Medical System	Sacramento	California
United States	Inland Northwest Research	Spokane	Washington
United States	University of South Florida	Tampa	Florida
United States	Georgetown University; Research Division, Psychiatry	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and severity of adverse events, with severity determined according to the Adverse Event Severity Grading Scale		Up to Approximately 24 Months
Primary	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
Primary	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
Primary	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
Primary	Percentage change from baseline in geometric means of CSF mHTT protein levels at Month 9		Baseline and Month 9
Primary	Change from baseline in composite Unified Huntington's Disease Rating Scale (cUHDRS) Scores (non-U.S. sites) at 16 months	Change in scores on the scale	Baseline to 16 Months
Primary	Change from baseline in Total Functional Capacity (TFC) Scores (U.S. sites) at 16 months	Change in scores on the scale	Baseline to 16 Months
Secondary	Change from baseline in MoCA Scores		From Baseline, Months 4, 8, 12, 16 and up to approximately Month 24
Secondary	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
Secondary	Change from baseline at 16 months for the assessments of TFC (non-U.S. sites) Scores		Baseline to 16 Months
Secondary	Change from baseline at 16 months for the assessments of cUHDRS (U.S. sites) Scores		Baseline to 16 Months
Secondary	Change from baseline at 16 months for the assessments of Symbol Digit Modalities Test (SDMT) Scores		Baseline to 16 Months
Secondary	Change from Baseline at 16 Months for the Assessments of Stroop Word Reading (SWR) Scores		Baseline to 16 Months
Secondary	Change from baseline at 16 months for the assessments of Total Motor Score (TMS)		Baseline to 16 Months
Secondary	Change from baseline in CSF Neurofilament light Chain (NfL) levels at 16 months		Baseline to 16 Months
Secondary	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
Secondary	Titers determined if ADAs are identified		From Baseline, Months 4, 8, 12, 16 and Up to Approximately Month 24