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

Roche

Status and phase: Active, not recruiting; Phase 2

Conditions: Huntington Disease

Treatments: Drug: Tominersen 100 mg; Drug: Placebo; Drug: Tominersen 60 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT05686551

2022-001991-32 (EudraCT Number)

BN42489

2023-503928-10-00 (EU Trial (CTIS) Number)

Other (Other Grant/Funding Number)

Details and patient eligibility

About

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).

Enrollment: 301 patients

Sex: All

Ages: 25 to 50 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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301 participants in 3 patient groups, including a placebo group

Tominersen 60 milligrams (mg)

Experimental group

Treatment:

Drug: Tominersen 60 mg

Placebo

Placebo Comparator group

Treatment:

Drug: Placebo

Tominersen 100 mg

Experimental group

Treatment:

Drug: Tominersen 100 mg