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; Drug: Placebo

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 criteria

DB Period:

• 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/m^2)

• Study companion

OLE Period:

• Participants must have completed the DB treatment period
• Participants must remain in the DB Safety follow-up period until OLE period starts

Exclusion criteria

DB Period:

• Current or previous use of an antisense oligonucleotide (ASO) (including small interfering ribonucleic acid [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 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

OLE Period:

• Early discontinuation from the DB treatment and the safety follow-up (SFU) periods
• Pregnant or breastfeeding, or with the intention of becoming pregnant during the study or within the timeframe in which contraception is required
• Current or previous use of an ASO other than tominersen (including small interfering RNA) or any other HTT-lowering therapy
• Hydrocephalus
• Received any active investigational treatment other than tominersen during or since completion of the DB treatment period

Key inclusions/exclusion criteria are listed here. Other protocol-defined I/E criteria may apply.

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

Description:

60 mg tominersen administered intrathecally (IT) every 16 weeks (Q16W). Tominersen will be administered in the DB period and the OLE period.

Treatment:

Drug: Tominersen

Placebo

Placebo Comparator group

Description:

Placebo will be administered IT, Q16W in the DB period.

Treatment:

Drug: Placebo

Tominersen 100 mg

Experimental group

Description:

100 mg tominersen administered IT, Q16W. Tominersen will be administered in the DB period and the OLE period.

Treatment:

Drug: Tominersen