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.
Study Details
Study Description
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 |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| 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
Primary Outcome Measures
- 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 36]
- 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 [Up to Approximately 16 Months]
Change in scores on the scale
- Change from baseline in Total Functional Capacity (TFC) Scores (U.S. sites) at 16 months [Baseline and 16 Months]
Change in scores on the scale
Secondary Outcome Measures
- Change from baseline in MoCA Scores [From Baseline, Months 4, 8, 12, 16 and up to approximately Month 36]
- 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]
- 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 36]
- Titers determined if ADAs are identified [From Baseline, Months 4, 8, 12, 16 and Up to Approximately Month 36]
Eligibility Criteria
Criteria
Key Inclusion Criteria
-
Signed study companion consent form. A study companion is required for all participants.
-
HD gene expansion mutation carrier status. CAP score of 400-500, inclusive, where CAP is calculated as follows:
Age x (CAG repeat length -33.66)
-Prodromal HD, defined as DCL 2 to 3, Total Motor Score (TMS) >6, Independence Scale (IS) = 100 (broadly equivalent to HD-ISS Stage 2), or early manifest HD, defined as DCL 4, TMS > 6, 100 >IS>/= 70, and TFC >/=8 (broadly equivalent to HD-ISS Stage 3)
Companion Inclusion Criteria
-
HD gene expansion mutation carrier status. CAP score of 400-500, inclusive, where CAP is calculated as follows: Age x (CAG repeat length -33.66)
-
Prodromal HD, defined as DCL 2 to 3, Total Motor Score (TMS) >6, Independence Scale (IS) = 100 (broadly equivalent to HD-ISS Stage 2), or early manifest HD, defined as DCL 4, TMS > 6, 100 >IS>/= 70, and TFC >/=8 (broadly equivalent to HD-ISS Stage 3)
-
Signed study companion consent form. A study companion is required for all participants.
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
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Dent Neurological | Amherst | New York | United States | 14226 |
Sponsors and Collaborators
- Hoffmann-La Roche
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BN42489
- Other