A Study to Investigate the Pharmacokinetics and Pharmacodynamics of RO7234292 (RG6042) in CSF and Plasma, and Safety and Tolerability Following Intrathecal Administration in Patients With Huntington's Disease

• ClinicalTrials.gov Identifier: NCT04000594
• Recruitment Status: Completed
• First Posted: June 27, 2019
• Last Update Posted: May 31, 2022
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: June 26, 2019
• First Posted Date: June 27, 2019
• Last Update Posted Date: May 31, 2022
• Actual Study Start Date: September 2, 2019
• Actual Primary Completion Date: January 18, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 24, 2020)

• Concentrations of RO7234292 in CSF (cerebrospinal fluid) [ Time Frame: Day 1, 2, 3, 4, 29, 43, 71, 127, and follow-up visit (6 months after last study drug administration) ]
• Concentrations of RO7234292 in Plasma [ Time Frame: Day 1, 2, 3, 4, 5, 28, 29, 30, 43, 71, 127, and follow-up visit (6 months after last study drug administration) ]
• mHTT (mutant Huntingtin) Concentration in CSF [ Time Frame: Days 1, 2, 3, 29, 43, 71, 127 and follow-up visit (6 months after last study drug administration) ]

Original Primary Outcome Measures (submitted: June 26, 2019)

• Concentrations of RO7234292 in CSF (cerebrospinal fluid) [ Time Frame: Day 1, 2, 3, 4, 29, 43, 71, 127, and follow-up visit (6 months after last study drug administration) ]
• Concentrations of RO7234292 in Plasma [ Time Frame: Day 1, 2, 3, 4, 5, 28, 29, 30, 43, 71, 127, and follow-up visit (6 months after last study drug administration) ]
• mHTT (mutant Huntingtin) Concentration in CSF [ Time Frame: Day -1, Day 1, 2, 3, 4, 29, 43, 71, 127, and follow-up visit (6 months after last study drug administration) ]

Current Secondary Outcome Measures (submitted: April 24, 2020)

• Incidence and Severity of Adverse Events [ Time Frame: Up to 6 months ]
• Percentage of Participants With Suicidal Ideation or Behavior, as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score [ Time Frame: Screening, Day -1, Day 28, Day 71, Day 127, and follow-up visit (6 months after last study drug administration) ]
  The Columbia-Suicide Severity Rating Scale (C-SSRS) is a structured tool to assess suicidal ideation and behavior. Four constructs are measured: severity of ideation, intensity of ideation, behavior, and lethality of actual suicide attempts. Binary (yes/no) data are collected for 10 categories, and composite endpoints based on the categories are followed over time to monitor patient safety.
• Incidence of Anti-Drug Antibodies (ADAs) [ Time Frame: Day 1, Day 28, and follow-up visit (6 months after last study drug administration) ]
• Titer and Antibody Subtype, determined if ADAs are Identified [ Time Frame: Day 1, Day 28, and follow-up visit (6 months after last study drug administration) ]
• Concentrations of RO7234292 in Urine [ Time Frame: Up to 72 hours ]

Original Secondary Outcome Measures (submitted: June 26, 2019)

• Incidence and Severity of Adverse Events [ Time Frame: Up to 6 months ]
• Percentage of Participants With Suicidal Ideation or Behavior, as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score [ Time Frame: Screening, Day -1, Day 28, Day 71, Day 127, and follow-up visit (6 months after last study drug administration) ]
  The Columbia-Suicide Severity Rating Scale (C-SSRS) is a structured tool to assess suicidal ideation and behavior. Four constructs are measured: severity of ideation, intensity of ideation, behavior, and lethality of actual suicide attempts. Binary (yes/no) data are collected for 10 categories, and composite endpoints based on the categories are followed over time to monitor patient safety.
• Incidence of Anti-Drug Antibodies (ADAs) [ Time Frame: Day 1, Day 28, and follow-up visit (6 months after last study drug administration) ]
• Titer and Antibody Subtype, determined if ADAs are Identified [ Time Frame: Day 1, Day 28, and follow-up visit (6 months after last study drug administration) ]
• Concentrations of RO7234292 in Urine [ Time Frame: Up to 96 hours ]

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

Descriptive Information

• Brief Title: A Study to Investigate the Pharmacokinetics and Pharmacodynamics of RO7234292 (RG6042) in CSF and Plasma, and Safety and Tolerability Following Intrathecal Administration in Patients With Huntington's Disease
• Official Title: An Open-Label Adaptive Multiple-Dose Study to Investigate the Pharmacokinetics and Pharmacodynamics of RO7234292 in CSF and Plasma, and Safety and Tolerability Following Intrathecal Administration in Patients With Huntington's Disease
• Brief Summary: Study BP40410 is an open-label, adaptive multiple-dose clinical study designed to characterize the PK of RO7234292 (RG6042) in plasma and CSF as well as the acute time course and recovery profile of CSF mHTT lowering in response to RO7234292 (RG6042) treatment after intrathecal (IT) administration of RO7234292 (RG6042) to patients with manifest Hungtington's disease (HD).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Huntingtons Disease

Intervention

Drug: RO7234292 (RG6042)

RO7234292 (RG6042) will be administered in two IT doses of the same dose level at an interval of 28 days during the treatment period (Day 1 and Day 29). Each dose of RO7234292 (RG6042) will be administered as a single IT bolus injection.

Other Name: Tominersen

Study Arms

• Experimental: Dose level 1 of RO7234292 (RG6042)
  Participants will receive dose level 1 of RO7234292 (RG6042) intrathecally on Day 1 and Day 29.
  Intervention: Drug: RO7234292 (RG6042)
• Experimental: Dose level 2 of RO7234292 (RG6042)
  Participants will receive dose level 2 of RO7234292 (RG6042) intrathecally on Day 1 and Day 29.
  Intervention: Drug: RO7234292 (RG6042)
• Experimental: Dose level 3 of RO7234292 (RG6042)
  Participants will receive dose level 3 of RO7234292 (RG6042) intrathecally on Day 1 and Day 29.
  Intervention: Drug: RO7234292 (RG6042)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 31, 2022): 12
• Original Estimated Enrollment (submitted: June 26, 2019): 20
• Actual Study Completion Date: January 18, 2022
• Actual Primary Completion Date: January 18, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Manifest HD diagnosis
• Independence Scale score of >=70.
• Genetically confirmed disease by direct deoxyribonucleic acid testing with a cytosine, adenine, and guanine base sequence found in DNA which is translated into glutamine (CAG) age product (CAP) score > 400.
• Ability to read the words "red," "blue," and "green" in the patient's native language.
• Ability to walk unassisted without a cane or walker and move about without a wheelchair on a daily basis as reviewed at screening and baseline visit.
• Ability to undergo and tolerate MRI scans.

Exclusion Criteria:

• 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.
• Current active psychosis, confusional state, or violent behavior.
• Any serious medical condition or clinically significant laboratory, vital signs, or ECG abnormalities at screening that, in the Investigator's judgment, precludes the patient's safe participation in and completion of the study.
• Clinical diagnosis of chronic migraines or history of low pressure headache after lumbar puncture requiring hospitalization or blood patch.
• Treatment with investigational therapy within 4 weeks prior to screening or 5 drug elimination half-lives of investigational therapy, whichever is longer.
• Concurrent or planned concurrent participation in any interventional clinical study, including explicit pharmacological and non-pharmacological interventions. Observational studies are acceptable.
• Unable or unsafe to perform lumbar puncture on the patient.
• Previous lumbar surgery that is likely, in the opinion of the Investigator or surgical team, to make IT catheter insertion or IT injection unduly difficult or hazardous.
• Poor peripheral venous access.
• Scoliosis or spinal deformity making IT injection not feasible in the outpatient setting.
• Preexisting intra-axial or extra-axial lesions as assessed by a centrally read MRI scan during the screening period.

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: Netherlands, United Kingdom

Administrative Information

• NCT Number: NCT04000594
• Other Study ID Numbers: BP40410; GEN-PEAK ( Other Identifier: Hoffmann-La Roche )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on Sharing of Clinical Study Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

• 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: May 2022