Clinical Trials in the USA / NCT05686551
Active, not recruiting
Phase 2
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 · tracked via the Priya Life Science USA tracker
Condition(s) studied
Huntington Disease
Investigational drug(s) / intervention(s)
TominersenPlacebo
Tominersen: Tominersen will be administered at the dose and schedule specified in the protocol.
Placebo: Matching placebo administered IT, Q16W during the DB period.
Study 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).
Eligibility
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.
Primary outcome measure(s)
- DB Period: Incidence and Severity of Adverse Events (AEs), With Severity Determined According to the AE Severity Grading Scale — Up to approximately 36 months
- DB Period: Change From Baseline in Clinical Laboratory Results - Cerebrospinal Fluid (CSF) White Blood Cell (WBC) — Baseline visit (Day 1), and Months 4, 8, 9, 12, 16
- DB Period: Change From Baseline in Clinical Laboratory Results - CSF Protein — Baseline visit (Day 1), and Months 4, 8, 9, 12, 16
- 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 — Baseline, Months 4, 8, 12, 16 and up to approximately 36 months
- DB Period: Percentage Change From Baseline in Geometric Means of CSF Mutant Huntingtin (mHTT) Protein Levels at Month 9 — Baseline, Month 9
- DB Period: 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 in scores on the scale. - DB Period: Change From Baseline in Total Functional Capacity (TFC) Scores (U.S. Sites) at 16 Months — Baseline to 16 months
Change in scores on the scale. - OLE Period: Incidence and Severity of AEs, With Severity Determined According to the AE Severity Grading Scale — Up to approximately 29 months
- OLE Period: Change Over Time in Clinical Laboratory Results - CSF WBC — Up to approximately 24 months
- OLE Period: Change Over Time in Clinical Laboratory Results - CSF Protein — Up to approximately 24 months
- OLE Period: Change From Baseline in Structural MRI Assessing Any New Abnormalities, Including Radiographic Features Consistent With Hydrocephalus and Other Relevant MRI Safety Findings — Up to approximately 29 months
Trial sites (70)
| Facility | City | Region | Status |
|---|---|---|---|
| Uab Medicine | Birmingham | Alabama | |
| Barrow Neurological Institute | Phoenix | Arizona | |
| University of California Davis Medical System | Sacramento | California | |
| CenExel Rocky Mountain Clinical Research, LLC | Englewood | Colorado | |
| Georgetown University | Washington D.C. | District of Columbia | |
| University of Florida | Gainesville | Florida | |
| University of South Florida | Tampa | Florida | |
| Northwestern University | Chicago | Illinois | |
| University of Iowa Hospitals and Clinics | Iowa City | Iowa | |
| John Hopkins University School of Medicine | Baltimore | Maryland | |
| Beth Israel Deaconess Medical Center | Boston | Massachusetts | |
| Henry Ford Hospital | Detroit | Michigan | |
| Dent Neurological Institute | Amherst | New York | |
| University of Pittsburgh | Pittsburgh | Pennsylvania | |
| Vanderbilt University Medical Center | Nashville | Tennessee | |
| The University of Texas Health Science Center at Houston | Houston | Texas | |
| EvergreenHealth Investigational Drug Services | Kirkland | Washington | |
| Inland Northwest Research | Spokane | Washington | |
| CINME | Buenos Aires | Argentina | |
| Hospital Ramos Mejía | CABA | Argentina | |
| INEBA | Capital Federal | Argentina | |
| Hospital Britanico de Buenos Aires | Ciudad Autonoma Buenos Aires | Argentina | |
| Monash Medical Centre | Clayton | Victoria | |
| Royal Melbourne Hospital | Parkville | Victoria | |
| Perron Institute for Neurological and Translational Science | Nedlands | Western Australia | |
| Uniklinik fuer Neurologie, Medizinische Universitaet Innsbruck | Innsbruck | Austria | |
| University of Alberta Hospital | Edmonton | Alberta | |
| Montreal Neurological Inst | Montreal | Quebec | |
| Rigshospitalet, Hukommelsesklinikken | København Ø | Denmark | |
| CHU Angers, Batiement Larrey 2, Neurologie | Angers | France | |
| Groupe Hospitalier Pellegrin | Bordeaux | France | |
| Hopital Henri Mondor | Créteil | France | |
| Hopital Roger Salengro Service de Neurologie | Lille | France | |
| CHU de la Timone - Hopital d Adultes | Marseille | France | |
| Hopital Gui de Chauliac | Montpellier | France | |
| CHU Strasbourg Hpital Hautepierre | Strasbourg | France | |
| CHU toulouse - Hôpital Purpan | Toulouse | France | |
| Uniklinik RWTH Aachen | Aachen | Germany | |
| Charité - Universitätsmed. Berlin, Klinik für Psychiatrie und Psychotherapie | Berlin | Germany | |
| St. Josef-Hospital, Neurologische Klinik der Ruhr-Uni | Bochum | Germany |
+ 30 more sites — see the full list on the official registry below.
More Hoffmann-La Roche trials in the USA
Other trials for the same condition
Official registry record
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
View NCT05686551 on ClinicalTrials.gov ↗ ← All trials in the USA