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.

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

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

Study Overview

• Status: Recruiting
• Conditions: Huntington Disease
• Intervention / Treatment: Drug: Tominersen 60 mg; Drug: Placebo; Drug: Tominersen 100 mg

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: BN42489 https://forpatients.roche.com/; Phone Number: 888-662-6728 (U.S. Only); Email: global-roche-genentech-trials@gene.com

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1056ABJ
    • Active, not recruiting
    • CINME
  • Caba, Argentina, C1221ADC
    • Recruiting
    • Hospital Ramos Mejia
  • Capital Federal, Argentina, C1192AAX
    • Recruiting
    • INEBA
  • Ciudad Autonoma Buenos Aires, Argentina, C1284AEB
    • Recruiting
    • Hospital Britanico de Buenos Aires
• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • Recruiting
      • WESTMEAD HOSPITAL; Deparment of Neurology
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Recruiting
      • Monash Medical Centre
    • Parkville, Victoria, Australia, 3050
      • Recruiting
      • Royal Melbourne Hospital; Department of Neurology
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Recruiting
      • Perron Institute for Neurological and Translational Science
• Austria
  • Innsbruck, Austria, 6020
    • Recruiting
    • Uniklinik fuer Neurologie, Medizinische Universitaet Innsbruck; Department fuer Neurologie
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z1
      • Recruiting
      • University of Alberta Hospital
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3S 1N2
      • Withdrawn
      • Centricity Research
  • Quebec
    • Montreal, Quebec, Canada, H3A 2B4
      • Recruiting
      • Montreal Neurological Inst; Clinical Research Unit
• Denmark
  • København Ø, Denmark, 2100
    • Recruiting
    • Rigshospitalet, Hukommelsesklinikken
• France
  • Angers Cedex 9, France, 49933
    • Recruiting
    • CHU Angers, Batiement Larrey 2, Neurologie
  • Bordeaux, France, 33076
    • Recruiting
    • Groupe Hospitalier Pellegrin; Service de Neurologie - 3ème étage
  • Creteil, France, 94010
    • Recruiting
    • Hopital Henri Mondor; Service de Neurologie
  • Lille, France
    • Recruiting
    • Hopital Roger Salengro Service de Neurologie
  • Marseille, France, 13005
    • Recruiting
    • CHU de la Timone - Hopital d Adultes; Service de Neurologie
  • Montpellier, France, 34295
    • Recruiting
    • Hopital Gui de Chauliac; Neurologie
  • Strasbourg, France, 67098
    • Recruiting
    • CHU Strasbourg Hôpital Hautepierre
  • Toulouse, France, 31059
    • Recruiting
    • CHU toulouse - Hôpital Purpan; Departement de Neurologie
• Germany
  • Aachen, Germany, 52074
    • Recruiting
    • Uniklinik RWTH Aachen; Klinik für Neurologie
  • Berlin, Germany, 10117
    • Recruiting
    • Charité - Universitätsmed. Berlin, Klinik für Psychiatrie und Psychotherapie; Abt. Neuropsychiatrie
  • Bochum, Germany, 44791
    • Recruiting
    • St. Josef-Hospital, Neurologische Klinik der Ruhr-Uni; Huntington-Center NRW, Abt. Neurodegeneration
  • Bonn, Germany, 53127
    • Recruiting
    • German Center for Neurodegenerative Diseases (DZNE)
  • Erlangen, Germany, 91054
    • Recruiting
    • Universitätsklinikum Erlangen, Abteilung Molekulare Neurologie
  • Lübeck, Germany, 23538
    • Recruiting
    • Universitätsklinikum Schleswig-Holstein / Campus Lübeck; Zentrum für Seltene Erkrankungen
  • Ulm, Germany, 89081
    • Recruiting
    • Universitätsklinikum Ulm; Klinik für Neurologie
• Italy
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40139
      • Recruiting
      • Ospedale Bellaria; Istituto delle Scienze Neurologiche
  • Lazio
    • Roma, Lazio, Italy, 00189
      • Recruiting
      • Azienda Ospedaliera Sant'Andrea; UOC Neurologia
  • Lombardia
    • Milano, Lombardia, Italy, 20133
      • Recruiting
      • Fondazione IRCCS Istituto Neurologico Carlo Besta; U.O.C. Genetica Medica-Neurogenetica
• New Zealand
  • Christchurch, New Zealand, 8011
    • Recruiting
    • New Zealand Brain Research Institute
  • Hamilton, New Zealand, 3240
    • Recruiting
    • Waikato Hospital; Neurology
• Poland
  • Gda?sk, Poland, 80-462
    • Recruiting
    • Szpital Sw. Wojciecha; Oddzial Neurologiczny
  • Krakow, Poland, 31-505
    • Recruiting
    • Krakowska Akademia Neurologii Sp z o.o. Centrum Neurologii K
  • Warszawa, Poland, 02-957
    • Active, not recruiting
    • Instytut Psychiatrii i Neurologii
• Portugal
  • Lisboa, Portugal, 1649-035
    • Recruiting
    • Hospital de Santa Maria; Servico de Neurologia
  • Torres Vedras, Portugal, 2560-280
    • Recruiting
    • CNS - Campus Neurologico
• Spain
  • Badajoz, Spain, 06080
    • Recruiting
    • Hospital Universitario de Badajoz; Servicio de Neurología
  • Barcelona, Spain, 08041
    • Recruiting
    • Hospital de la Santa Creu i Sant Pau; Servicio de Neurologia
  • Burgos, Spain, 09006
    • Recruiting
    • Hospital Universitario de Burgos. Servicio de Neurología
  • Madrid, Spain, 28034
    • Recruiting
    • Hospital Ramon y Cajal; Servicio de Neurologia
  • Sevilla, Spain, 41009
    • Active, not recruiting
    • Hospital Universitario Virgen Macarena; Servicio de Neurologia
  • Valencia, Spain, 46026
    • Active, not recruiting
    • Hospital Universitario la Fe; Servicio de Neurologia
  • Vizcaya
    • Barakaldo, Vizcaya, Spain, 48903
      • Recruiting
      • Hospital de Cruces; Servicio de Neurologia
• Switzerland
  • Basel, Switzerland, 4031
    • Recruiting
    • Universitätsspital Basel; Neurologie
  • Gümligen, Switzerland, 3073
    • Recruiting
    • Neurozentrum Siloah
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • Active, not recruiting
    • University Hospitals Birmingham NHS Foundation Trust
  • Cambridge, United Kingdom, CB2 0QQ
    • Recruiting
    • Addenbrookes Hospital
  • Chinnor, United Kingdom, OX3 9DU
    • Recruiting
    • John Radcliffe Hospital; Neurosciences
  • Leeds, United Kingdom, LS7 4SA
    • Recruiting
    • Chapel Allerton Hospital; Clinical Genetics
  • London, United Kingdom, NW1 2PG
    • Recruiting
    • UCL Hospital NHS Trust
  • Southampton, United Kingdom, SO16 6YD
    • Recruiting
    • Southampton University Hospitals NHS Trust
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Recruiting
      • Uab Medicine
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Recruiting
      • Barrow Neurological Institute
  • California
    • La Jolla, California, United States, 92037-1337
      • Withdrawn
      • University of California San Diego
    • Sacramento, California, United States, 95817
      • Recruiting
      • University of California Davis Medical System
  • Colorado
    • Englewood, Colorado, United States, 80113
      • Recruiting
      • CenExel Rocky Mountain Clinical Research, LLC
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Recruiting
      • Georgetown University; Research Division, Psychiatry
  • Florida
    • Gainesville, Florida, United States, 32607
      • Recruiting
      • University of Florida
    • Tampa, Florida, United States, 33613
      • Recruiting
      • University of South Florida
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern University
  • Iowa
    • Iowa City, Iowa, United States, 52242-1083
      • Recruiting
      • University of Iowa Hospitals and Clinics
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • John Hopkins University School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Beth Israel Deaconess Medical Center
  • New York
    • Amherst, New York, United States, 14226
      • Recruiting
      • Dent Neurological Institute
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • University of Pittsburgh
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Active, not recruiting
      • Vanderbilt University Medical Center
  • Washington
    • Kirkland, Washington, United States, 98034
      • Recruiting
      • Evergreen Health Care Center
    • Spokane, Washington, United States, 99202
      • Recruiting
      • Inland Northwest Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 50 years (Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Matching placebo administered intrathecally every 16 weeks
Experimental: Tominersen 60 mg	Drug: Tominersen 60 mg; 60 mg tominersen administered intrathecally every 16 weeks
Experimental: Tominersen 100 mg	Drug: Tominersen 100 mg; 100 mg tominersen administered intrathecally every 16 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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) White Blood Cell (WBC) (1/uL)		From Baseline Visit (Day 1), and Months 4, 8, 9, 12, 16
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 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
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
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 Outcome Measures

Outcome Measure	Time Frame
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
Change from baseline in MoCA Scores	From Baseline, Months 4, 8, 12, 16 and up to approximately Month 24
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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): February 3, 2023
• Primary Completion (Estimated): February 28, 2026
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: December 16, 2022
• First Submitted That Met QC Criteria: January 6, 2023
• First Posted (Actual): January 17, 2023

Study Record Updates

• Last Update Posted (Actual): March 29, 2024
• Last Update Submitted That Met QC Criteria: March 28, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Prodromal and Early Manifest Huntington's Disease
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Dyskinesias; Heredodegenerative Disorders, Nervous System; Dementia; Cognition Disorders; Chorea; Huntington Disease
• Other Study ID Numbers: BN42489; Other (Other Identifier: GENERATION HD2)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No