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

• ClinicalTrials.gov Identifier: NCT03761849
• Recruitment Status: Completed
• First Posted: December 3, 2018
• Last Update Posted: September 22, 2022
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: November 30, 2018
• First Posted Date: December 3, 2018
• Last Update Posted Date: September 22, 2022
• Actual Study Start Date: January 23, 2019
• Actual Primary Completion Date: March 17, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 30, 2018)

• Change from Baseline in the Composite Unified Huntington's Disease Rating Scale (cUHDRS) [ Time Frame: Baselined, Week 101 ]
• Change From Baseline in the TFC Score [ Time Frame: Baseline, Week 101 ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 19, 2019)

• Change From Baseline in Total Motor Score (TMS) [ Time Frame: Baseline, Week 101 ]
• Change From Baseline in Symbol Digit Modalities Test (SDMT) [ Time Frame: Baseline, Week 101 ]
• Change From Baseline in Stroop Word Reading (SWR) Test [ Time Frame: Baseline, Week 101 ]
• Change From Baseline in the Clinical Global Impression, Severity Scale (CGI-S) [ Time Frame: Baseline, Week 101 ]
• Percentage of Patients with a Decrease From Baseline of >=1 point on the TFC [ Time Frame: Baseline, Week101 ]
• Percentage of Patients With a Decline From Baseline of >=1.2 Points on the cUHDRS [ Time Frame: Baseline, Week 101 ]
• Percentage of Patients With an Unchanged or Improved Score on the Clinical Global Impression, Change Scale (CGI-C) Score [ Time Frame: Baseline to Week 101 ]
• Percentage of Participants with Adverse Events [ Time Frame: Up to 117 Weeks (29 months) ]
• Change From Baseline in Montreal Cognitive Assessment (MoCA) [ Time Frame: Screening, Baseline, Weeks 5, 21, 37, 53, 69, 85 and 101 and early treatment termination ]
• Percentage of Participants With Suicidal Ideation or Behavior, as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score [ Time Frame: Screening, Baseline, Weeks 5, 13, 21, 29, 37, 45, 53, 61, 69, 77, 85, 93, 101, 117, end of treatment for early treatment termination and at early treatment termination ]
• Concentration of RO7234292 in Plasma [ Time Frame: Baseline, Weeks 13, 21, 37, 53, 69, 85, and 101 and early treatment termination ]
• Trough Concentration of RO7234292 in CSF [ Time Frame: Baseline, Weeks 13, 21, 37, 53, 69, 85, and 101 and early treatment termination ]
• Incidence of Anti-Drug Antibodies (ADAs) [ Time Frame: Baseline, Weeks 13, 21, 37, 53, 69, 85, and 101 and early treatment termination and safety follow-up visit ]
• Titer and Antibody Subtype, determined if ADAs are Identified [ Time Frame: Baseline, Weeks 13, 21, 37, 53, 69, 85, and 101 and early treatment termination and safety follow-up visit ]
• Change From Baseline in CSF mHTT Protein Level [ Time Frame: Baseline, Week 101 ]
• Change From Baseline in Whole and Regional Brain Volumes, as detrmined by structural magnetic resonance imaging (MRI) [ Time Frame: Baseline, Week 101 ]
• Change From Baseline in CSF Neurofilament Light Chain (NfL) Proteint Level [ Time Frame: Baseline, Week 101 ]

Original Secondary Outcome Measures (submitted: November 30, 2018)

• Change From Baseline in Total Motor Score (TMS) [ Time Frame: Baseline, Week 101 ]
• Change From Baseline in Symbol Digit Modalities Test (SDMT) [ Time Frame: Baseline, Week 101 ]
• Change From Baseline in Stroop Word Reading (SWR) Test [ Time Frame: Baseline, Week 101 ]
• Change From Baseline in the Clinical Global Impression, Severity Scale (CGI-S) [ Time Frame: Baseline, Week 101 ]
• Percentage of Patients with a Decrease From Baseline of >=1 point on the TFC [ Time Frame: Baseline, Week101 ]
• Percentage of Patients With a Decline From Baseline of >=1.2 Points on the cUHDRS [ Time Frame: Baseline, Week 101 ]
• Percentage of Patients With an Unchanged or Improved Score on the Clinical Global Impression, Change Scale (CGI-C) Score [ Time Frame: Baseline to Week 101 ]
• Percentage of Participants with Adverse Events [ Time Frame: Up to 117 Weeks (29 months) ]
• Change From Baseline in Montreal Cognitive Assessment (MoCA) [ Time Frame: Screening, Baseline, Weeks 5, 21, 37, 53, 69, 85 and 101 and early treatment termination ]
• Percentage of Participants With Suicidal Ideation or Behavior, as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score [ Time Frame: Screening, Baseline, Weeks 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, 81, 85, 89, 93, 97, 101, end of treatment for early treatment termination and at early treatment termination ]
• Concentration of RO7234292 in Plasma [ Time Frame: Baseline, Weeks 13, 21, 37, 53, 69, 85, and 101 and early treatment termination ]
• Trough Concentration of RO7234292 in CSF [ Time Frame: Baseline, Weeks 13, 21, 37, 53, 69, 85, and 101 and early treatment termination ]
• Incidence of Anti-Drug Antibodies (ADAs) [ Time Frame: Baseline, Weeks 13, 21, 37, 53, 69, 85, and 101 and early treatment termination and safety follow-up visit ]
• Titer and Antibody Subtype, determined if ADAs are Identified [ Time Frame: Baseline, Weeks 13, 21, 37, 53, 69, 85, and 101 and early treatment termination and safety follow-up visit ]
• Change From Baseline in CSF mHTT Protein Level [ Time Frame: Baseline, Week 101 ]
• Change From Baseline in Whole and Regional Brain Volumes, as detrmined by structural magnetic resonance imaging (MRI) [ Time Frame: Baseline, Week 101 ]
• Change From Baseline in CSF Neurofilament Light Chain (NfL) Proteint Level [ Time Frame: Baseline, Week 101 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate the Efficacy and Safety of Intrathecally Administered RO7234292 (RG6042) in Participants With Manifest Huntington's Disease
• Official Title: A Randomized, Multicenter, Double-Blind, Placebo-Controlled, Phase III Clinical Study to Evaluate the Efficacy and Safety of Intrathecally Administered RO7234292 (RG6042) in Patients With Manifest Huntington's Disease
• Brief 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Huntingtons Disease

Intervention

• Drug: RO7234292
  Intrathecal injection
  Other Name: Tominersen
• Drug: Placebo
  Intrathecal injection

Study Arms

• Experimental: RO7234292 Q8W
  RO4234292 is administered intrathecally every 8 weeks.
  Intervention: Drug: RO7234292
• Experimental: RO7234292 Q16W
  RO7234292 is administered intrathecally every 16 weeks. Participants in this arm will also receive placebo at alternate weeks to keep the blind.
  Interventions:

  • Drug: RO7234292
  • Drug: Placebo
• Placebo Comparator: Placebo
  Placebo will be administered every 8 weeks by IT injection.
  Intervention: Drug: Placebo

Publications *

• Rodrigues FB, Ferreira JJ, Wild EJ. Huntington's Disease Clinical Trials Corner: June 2019. J Huntingtons Dis. 2019;8(3):363-371. doi: 10.3233/JHD-199003.
• Rodrigues FB, Quinn L, Wild EJ. Huntington's Disease Clinical Trials Corner: January 2019. J Huntingtons Dis. 2019;8(1):115-125. doi: 10.3233/JHD-190001.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 17, 2022): 899
• Original Estimated Enrollment (submitted: November 30, 2018): 660
• Actual Study Completion Date: March 17, 2022
• Actual Primary Completion Date: March 17, 2022 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 25 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Argentina, Austria, Canada, Chile, Denmark, France, Germany, Italy, Japan, Netherlands, New Zealand, Poland, Russian Federation, Spain, Switzerland, United Kingdom, United States
• Removed Location Countries: China

Administrative Information

• NCT Number: NCT03761849
• Other Study ID Numbers: BN40423; GENERATION HD1 ( Other Identifier: Hoffmann-La Roche )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Same as current
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: September 2022