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Phase 3 N=899 Randomized Quadruple-blind Treatment

A Study to Evaluate the Efficacy and Safety of Intrathecally Administered RO7234292 (RG6042) in Participants With Manifest Huntington's Disease

Huntingtons Disease

Enrolled (actual)
899
Serious AEs
12.9%
Results posted
Nov 2023
Primary outcome: Primary: Change From Baseline in the Composite Unified Huntington's Disease Rating Scale (cUHDRS) Score-Z Score — 0.103; -0.367; -0.139; -1.173 Scores on a Scale

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
RO7234292 (Drug); Placebo (Drug)
Age
Adult, Older Adult · 25+ yrs
Sex
All
Sponsor
Hoffmann-La Roche
Primary completion
Mar 2022

Outcome Measures

OutcomeResultp-value
PRIMARY
Change From Baseline in the Composite Unified Huntington's Disease Rating Scale (cUHDRS) Score-Z Score
0.103; -0.367; -0.139; -1.173; -0.793; -0.630
PRIMARY
Change From Baseline in the Total Functional Capacity (TFC) Score
0.150; -0.463; -0.460; -1.284; -0.921; -0.883
SECONDARY
Change From Baseline in Total Motor Score (TMS)
-1.977; 2.570; 1.493; 4.028; 3.524; 3.513
SECONDARY
Change From Baseline in Symbol Digit Modalities Test (SDMT) Scores' Least Squares Mean Values
1.865; -1.166; 1.204; -2.641; -0.996; -0.216
SECONDARY
Change From Baseline in Stroop Word Reading (SWR) Test Scores' Least Squares Mean Values
-1.397; 0.469; -1.036; -5.224; -3.949; -2.555
SECONDARY
Change From Baseline in the Clinical Global Impression, Severity Scale (CGI-S) Scores' Least Squares Mean Values
0.662; 0.640; 0.545
SECONDARY
Percentage of Patients With a Decrease From Baseline of >=1 Point on the Total Functional Capacity (TFC) Score
55.7; 50.3; 49.5; 44.3; 49.7; 43.7
SECONDARY
Percentage of Patients With a Decline From Baseline of >=1.2 Points on the Composite Unified Huntington's Disease Rating Scale-cUHDRS Score
44.5; 32.1; 29.7; 55.5; 67.9; 70.3
SECONDARY
Percentage of Patients With an Unchanged or Improved Score on the Clinical Global Impression, Change Scale Score
55.4; 59.6; 56.3; 44.6; 40.4; 43.7
SECONDARY
Percentage of Participants With Adverse Events
77.8; 80.0; 61.1; 92.3; 90.0; 93.1
SECONDARY
Change From Baseline in Montreal Cognitive Assessment (MoCA)
-0.07; 0.10; 0.33; 0.44; 0.39; 0.45
SECONDARY
Percentage of Participants With Suicidal Ideation or Behavior, as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score
0; 8.6; 2.8; 9.7; 11.2; 10.4
SECONDARY
Concentration of RO7234292 in Plasma
0.511; 0.203; 0.20; 0.06; 1.63; 0.28
SECONDARY
Trough Concentration of RO7234292 in Cerebrospinal Fluid (CSF)
4.44; 1.51; 1.54; 0.70; 1.74; 0.55
SECONDARY
Incidence of Anti-Drug Antibodies (ADAs).
94.3; 91.7; 91.4; 91.7; 2.9; 0
SECONDARY
Titer and Antibody Subtype, Determined if ADAs Are Identified
SECONDARY
Change From Baseline in CSF mHTT Protein Level
SECONDARY
Change From Baseline in Whole and Regional Brain Volumes, as Detrmined by Structural Magnetic Resonance Imaging (MRI)
0.996; 0.330; 1.124; 1.537; 3.785; 2.011
SECONDARY
Change From Baseline in CSF Neurofilament Light Chain (NfL) Proteint Level
12.233; 34.548; 16.553; 31.893; 5.406; 3.365

Summary

This study will evaluate the efficacy, safety, and biomarker effects of RO7234292 (RG6042) compared with placebo in participants with manifest Huntington's disease (HD)

Eligibility Criteria

Inclusion Criteria

  • Manifest HD diagnosis, defined as a DCL score of 4
  • Independence Scale (IS) score >= 70
  • Genetically confirmed disease by direct DNA testing with a CAP score >400
  • Clinical assessment to ensure individual has intact functional independence at baseline to maintain self-care and core activities of daily living (ADLs).

Exclusion Criteria

  • Any serious medical condition or clinically significant laboratory, or vital sign abnormality or claustrophobia at screening that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study
  • Pregnant or breastfeeding, or intending to become pregnant during the study or within 5 months after the final dose of study drug
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03761849). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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