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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.

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ClinicalTrials.gov Identifier: NCT05686551
Recruitment Status : Recruiting
First Posted : January 17, 2023
Last Update Posted : March 29, 2024
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Description
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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.

Condition or disease Intervention/treatment Phase
Huntington Disease Drug: Tominersen 60 mg Drug: Placebo Drug: Tominersen 100 mg Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : February 3, 2023
Estimated Primary Completion Date : February 28, 2026
Estimated Study Completion Date : April 1, 2027

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Tominersen 60 mg Drug: Tominersen 60 mg
60 mg tominersen administered intrathecally every 16 weeks
Placebo Comparator: Placebo Drug: Placebo
Matching placebo administered intrathecally every 16 weeks
Experimental: Tominersen 100 mg Drug: Tominersen 100 mg
100 mg tominersen administered intrathecally every 16 weeks


Outcome Measures
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Primary Outcome Measures :
  1. Incidence and severity of adverse events, with severity determined according to the Adverse Event Severity Grading Scale [ Time Frame: Up to Approximately 24 Months ]
  2. Change from baseline in clinical laboratory results - Cerebrospinal fluid (CSF) White Blood Cell (WBC) (1/uL) [ Time Frame: From Baseline Visit (Day 1), and Months 4, 8, 9, 12, 16 ]
  3. Change from baseline in clinical laboratory results Cerebrospinal fluid (CSF) protein (g/L) [ Time Frame: From Baseline Visit (Day 1), and Months 4, 8, 9, 12, 16 ]
  4. Change in baseline in structural MRI assessing any new abnormalities including radiographic features consistent with hydrocephalus and other relevant MRI safety findings [ Time Frame: From Baseline, Months 4, 8, 12, 16 and Up to Approximately Month 24 ]
  5. Percentage change from baseline in geometric means of CSF mHTT protein levels at Month 9 [ Time Frame: Baseline and Month 9 ]
  6. Change from baseline in composite Unified Huntington's Disease Rating Scale (cUHDRS) Scores (non-U.S. sites) at 16 months [ Time Frame: Baseline to 16 Months ]
    Change in scores on the scale

  7. Change from baseline in Total Functional Capacity (TFC) Scores (U.S. sites) at 16 months [ Time Frame: Baseline to 16 Months ]
    Change in scores on the scale


Secondary Outcome Measures :
  1. Change from baseline in MoCA Scores [ Time Frame: From Baseline, Months 4, 8, 12, 16 and up to approximately Month 24 ]
  2. 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 [ Time Frame: Up to Approximately 24 Months ]
  3. Change from baseline at 16 months for the assessments of TFC (non-U.S. sites) Scores [ Time Frame: Baseline to 16 Months ]
  4. Change from baseline at 16 months for the assessments of cUHDRS (U.S. sites) Scores [ Time Frame: Baseline to 16 Months ]
  5. Change from baseline at 16 months for the assessments of Symbol Digit Modalities Test (SDMT) Scores [ Time Frame: Baseline to 16 Months ]
  6. Change from Baseline at 16 Months for the Assessments of Stroop Word Reading (SWR) Scores [ Time Frame: Baseline to 16 Months ]
  7. Change from baseline at 16 months for the assessments of Total Motor Score (TMS) [ Time Frame: Baseline to 16 Months ]
  8. Change from baseline in CSF Neurofilament light Chain (NfL) levels at 16 months [ Time Frame: Baseline to 16 Months ]
  9. Incidence of anti-drug antibodies (ADAs) at specified timepoints relative to the prevalence of ADAs at baseline [ Time Frame: From Baseline, Months 4, 8, 12, 16 and Up to Approximately Month 24 ]
  10. Titers determined if ADAs are identified [ Time Frame: From Baseline, Months 4, 8, 12, 16 and Up to Approximately Month 24 ]

Eligibility Criteria
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Ages Eligible for Study:   25 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05686551


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

Locations
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Sponsors and Collaborators
Hoffmann-La Roche
More Information
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT05686551    
Other Study ID Numbers: BN42489
Other ( Other Identifier: GENERATION HD2 )
First Posted: January 17, 2023    Key Record Dates
Last Update Posted: March 29, 2024
Last Verified: March 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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).
Supporting Materials: Study Protocol

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hoffmann-La Roche:
Prodromal and Early Manifest Huntington's Disease
Additional relevant MeSH terms:
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Huntington Disease
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Dementia
Chorea
Dyskinesias
 Movement Disorders
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Cognition Disorders
Neurocognitive Disorders
Mental Disorders