Clinical trial

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

Name

BN42489

Description

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

Trial arms

Trial start

2023-02-03

Estimated PCD

2026-02-28

Trial end

2027-04-01

Status

Recruiting

Phase

Early phase I

Treatment

Tominersen 60 mg

60 mg tominersen administered intrathecally every 16 weeks

Arms:

Tominersen 60 mg

Placebo

Matching placebo administered intrathecally every 16 weeks

Arms:

Placebo

Tominersen 100 mg

100 mg tominersen administered intrathecally every 16 weeks

Arms:

Tominersen 100 mg

Size

300

Primary endpoint

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

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

Percentage change from baseline in geometric means of CSF mHTT protein levels at Month 9

Baseline and Month 9

Change from baseline in composite Unified Huntington's Disease Rating Scale (cUHDRS) Scores (non-U.S. sites) at 16 months

Baseline to 16 Months

Change from baseline in Total Functional Capacity (TFC) Scores (U.S. sites) at 16 months

Baseline to 16 Months

Eligibility 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

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 300, 'type': 'ESTIMATED'}}

Updated at

2024-04-29

1 organization

2 products

1 indication

Organization

Product

Product

Indication