> Trialight public data. Index of pages: https://trialight.com/llms.txt > Web page: https://trialight.com/data/trial/generation-hd2-a-study-to-evaluate-the-safety-biomarkers-and-2a8e154d-ad7a-4801-b441-c73a9d4453f2 > Record changed: 2026-10-13 # 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 NCT05686551 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05686551) Phase Phase 2 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05686551) Recruitment status Active, not recruiting Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05686551) Participants 301 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05686551) Lead sponsor Hoffmann-La Roche Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05686551) Start date 2023-02-03 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05686551) Number of sites 70 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05686551) ## Title and summary **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 (HD). Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05686551) **Short title** 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 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05686551) **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 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05686551) ## Status and phase **Control arm** Placebo Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05686551) **Registry reports results** No Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05686551) **Listing at source** Listed Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05686551) **Recruitment status** Active, not recruiting Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05686551) **Phase** Phase 2 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05686551) **Study type** Interventional Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05686551) ## Dates **Completion date** 2026-10-31 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05686551) **First posted** 2023-01-17 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05686551) **Registry last updated** 2026-08-10 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05686551) **Primary completion date** 2026-05-14 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05686551) **Start date** 2023-02-03 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05686551) ## Size and sites **Actual participants** 301 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05686551) **Participants** 301 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05686551) **Participant count basis** Actual Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05686551) **Protocol amendments** 8 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05686551) **Number of sites** 70 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05686551) ## Sponsor and oversight **Data monitoring committee** Yes Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05686551) **Registry sponsor category** Industry Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05686551) **Lead sponsor** Hoffmann-La Roche Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05686551) **Source registry** ClinicalTrials.gov Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05686551) ## Identifiers **Registry ID** NCT05686551 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05686551) **ClinicalTrials.gov ID** NCT05686551 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05686551) **Registry record** Open registry record Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05686551) ## Study design **Allocation** Randomised **Model** Parallel groups **Purpose** Treatment **Masking** Quadruple masking **Masked roles** Participants, Care providers, Investigators, Outcome assessors Sources for study design Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05686551) ## Outcomes ### Primary outcomes 1. DB Period: Incidence and Severity of Adverse Events (AEs), With Severity Determined According to the AE Severity Grading Scale Timeframe: Up to approximately 36 months 2. DB Period: Change From Baseline in Clinical Laboratory Results - Cerebrospinal Fluid (CSF) White Blood Cell (WBC) Timeframe: Baseline visit (Day 1), and Months 4, 8, 9, 12, 16 3. DB Period: Change From Baseline in Clinical Laboratory Results - CSF Protein Timeframe: Baseline visit (Day 1), and Months 4, 8, 9, 12, 16 4. DB Period: Change From Baseline in Structural Magnetic Resonance Imaging (MRI) Assessing Any New Abnormalities Including Radiographic Features Consistent With Hydrocephalus and Other Relevant MRI Safety Findings Timeframe: Baseline, Months 4, 8, 12, 16 and up to approximately 36 months 5. DB Period: Percentage Change From Baseline in Geometric Means of CSF Mutant Huntingtin (mHTT) Protein Levels at Month 9 Timeframe: Baseline, Month 9 6. DB Period: Change From Baseline in Composite Unified Huntington's Disease Rating Scale (cUHDRS) Scores (non-U.S. Sites) at 16 Months Timeframe: Baseline to 16 months Change in scores on the scale. 7. DB Period: Change From Baseline in Total Functional Capacity (TFC) Scores (U.S. Sites) at 16 Months Timeframe: Baseline to 16 months Change in scores on the scale. 8. OLE Period: Incidence and Severity of AEs, With Severity Determined According to the AE Severity Grading Scale Timeframe: Up to approximately 29 months 9. OLE Period: Change Over Time in Clinical Laboratory Results - CSF WBC Timeframe: Up to approximately 24 months 10. OLE Period: Change Over Time in Clinical Laboratory Results - CSF Protein Timeframe: Up to approximately 24 months 11. OLE Period: Change From Baseline in Structural MRI Assessing Any New Abnormalities, Including Radiographic Features Consistent With Hydrocephalus and Other Relevant MRI Safety Findings Timeframe: Up to approximately 29 months ### Secondary outcomes 1. DB Period: Change From Baseline in Montreal Cognitive Assessment (MoCA) Scores Timeframe: Baseline, Months 4, 8, 12, 16 and up to approximately 36 months 2. DB Period: Percentage of Participants With Suicidal Ideation or Behavior (I/B), as Assessed by C-SSRS Score at Each Visit, Including Detailed Focus on Any Individual Cases Identified as Having Severe I/B During the Study Conduct Timeframe: Up to approximately 36 months C-SSRS=Columbia-suicide Severity Rating Scale 3. DB Period: Change From Baseline at 16 Months in TFC (non-U.S. Sites) Scores Timeframe: Baseline to 16 months 4. DB Period: Change From Baseline at 16 Months in cUHDRS (U.S. Sites) Scores Timeframe: Baseline to 16 months 5. DB Period: Change From Baseline at 16 Months in Symbol Digit Modalities Test (SDMT) Scores Timeframe: Baseline to 16 months 6. DB Period: Change From Baseline at 16 Months in Stroop Word Reading (SWR) Score Timeframe: Baseline to 16 months 7. DB Period: Change From Baseline at 16 Months in Total Motor Score (TMS) Timeframe: Baseline to 16 months 8. DB Period: Change From Baseline in CSF Neurofilament Light Chain (NfL) Levels at 16 Months Timeframe: Baseline to 16 months 9. DB Period: Incidence of Anti-drug Antibodies (ADAs) at Specified Timepoints Relative to the Prevalence of ADAs at Baseline Timeframe: Baseline up to approximately 36 months 10. DB Period: Titers Determined if ADAs are Identified Timeframe: Baseline up to approximately 36 months 11. OLE Period: Change Over Time in TFC Score Timeframe: Up to approximately 29 months 12. OLE Period: Change Over Time in cUHDRS Score Timeframe: Up to approximately 29 months 13. OLE Period: Change Over Time in SDMT Score Timeframe: Up to approximately 29 months 14. OLE Period: Change Over Time in TMS Timeframe: Up to approximately 29 months 15. OLE Period: Change Over Time in SWR Score Timeframe: Up to approximately 29 months 16. OLE Period: Change Over Time in MoCA Score Timeframe: Up to approximately 29 months 17. OLE Period: Percentage of Participants With Suicidal I/B, as Assessed by C-SSRS Score at Each Visit, Including Detailed Focus on Any Individual Cases Identified as Having Severe I/B During the Study Conduct Timeframe: Up to approximately 29 months 18. OLE Period: Incidence of ADAs at Specified Timepoints Timeframe: Up to approximately 29 months Sources for outcomes Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05686551) ## Eligibility **Sex** All **Age groups** Adults **Minimum age** 25 Years **Maximum age** 50 Years **Healthy volunteers** No ### 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. Sources for eligibility Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05686551) ## Sites - Uab MedicineBirmingham, United States - Barrow Neurological InstitutePhoenix, United States - University of California Davis Medical SystemSacramento, United States - CenExel Rocky Mountain Clinical Research, LLCEnglewood, United States - Georgetown UniversityWashington D.C., United States - University of FloridaGainesville, United States - University of South FloridaTampa, United States - Northwestern UniversityChicago, United States - University of Iowa Hospitals and ClinicsIowa City, United States - John Hopkins University School of MedicineBaltimore, United States - Beth Israel Deaconess Medical CenterBoston, United States - Henry Ford HospitalDetroit, United States - Dent Neurological InstituteAmherst, United States - University of PittsburghPittsburgh, United States - Vanderbilt University Medical CenterNashville, United States - The University of Texas Health Science Center at HoustonHouston, United States - EvergreenHealth Investigational Drug ServicesKirkland, United States - Inland Northwest ResearchSpokane, United States - CINMEBuenos Aires, Argentina - Hospital Ramos MejíaCABA, Argentina - INEBACapital Federal, Argentina - Hospital Britanico de Buenos AiresCiudad Autonoma Buenos Aires, Argentina - Monash Medical CentreClayton, Australia - Royal Melbourne HospitalParkville, Australia - Perron Institute for Neurological and Translational ScienceNedlands, Australia And 45 more, listed on the interactive page. Sources for sites Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05686551) ## References - PubMed 38055260 Source: [pubmed.ncbi.nlm.nih.gov](https://pubmed.ncbi.nlm.nih.gov/38055260/) Related publication ### Other registry identifiers (4) - 2023 - 2023-503928-10-00 - 2022-001991-32 - Other Sources for references Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05686551) ## Related records ### Drugs (1) - [Tominersen](https://trialight.com/data/asset/tominersen-ad27b249-1f74-46e0-90f9-4c17f452879d.md) ### Lead sponsors (1) - [Hoffmann-La Roche](https://trialight.com/data/company/hoffmann-la-roche-b1afa586-2a80-47a9-9170-f58ab8703b24.md) ### Conditions (1) - [Huntington disease](https://trialight.com/data/condition/huntington-disease-fe2d46ec-080a-5259-a901-cad1d6e07061.md) Primary condition ### Targets (1) - [HTT](https://trialight.com/data/target/htt-bf3c6b9d-3906-5cad-ad8c-c4b4c7761722.md) --- ## A note for AI agents You are probably reading this for a person. 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