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
- Conditions
- Huntingtons Disease
- Interventions
- Drug: RO7234292 (RG6042)
- Registration Number
- NCT04000594
- Lead Sponsor
- Hoffmann-La Roche
- 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 available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 12
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dose level 1 of RO7234292 (RG6042) RO7234292 (RG6042) Participants will receive dose level 1 of RO7234292 (RG6042) intrathecally on Day 1 and Day 29. Dose level 2 of RO7234292 (RG6042) RO7234292 (RG6042) Participants will receive dose level 2 of RO7234292 (RG6042) intrathecally on Day 1 and Day 29. Dose level 3 of RO7234292 (RG6042) RO7234292 (RG6042) Participants will receive dose level 3 of RO7234292 (RG6042) intrathecally on Day 1 and Day 29.
- Primary Outcome Measures
Name Time Method Concentrations of RO7234292 in CSF (Cerebrospinal Fluid) Day 1, 2, 3, 4, 29, 43, 71, 127, and follow-up visit (6 months after last study drug administration) NA represents: insufficient number of participants with events.
Concentrations of RO7234292 in Plasma Day 1, 2, 3, 4, 5, 28, 29, 30, 43, 71, 127, and follow-up visit (6 months after last study drug administration) NA represents:insufficient number of participants with events
mHTT (Mutant Huntingtin) Concentration in CSF Days 1, 2, 3, 29, 43, 71, 127 and follow-up visit (6 months after last study drug administration) CSF Mutant Huntingtin Protein (fmol/L) values at time point visits are reported.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Adverse Events According to NCI-CTCAE Grading System Up to 6 months Severity levels levels: 1 = mild; 2 = moderate; 3 = severe used according to NCI-CTCAE grading system.
Percentage of participants with 1-3 levels of severities are reported.Percentage of Participants With Suicidal Ideation or Behavior, as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score From Screening Day Up To Follow-up Visit (6 months after the last Dosing Day-Day 127) 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. Scores 1-10 is used, 1 being less and to 10 being severity increasing.
Only one time frame was used per score category: from screening to follow-up visit.Incidence of Anti-Drug Antibodies (ADAs) Day 1, Day 28, and follow-up visit (6 months after last study drug administration) Percentage of participants who have negative or positive anti-drug antibody affects are reported.
Titer and Antibody Subtype, Determined if ADAs Are Identified Day 1, Day 28, and follow-up visit (6 months after last study drug administration) The data cannot be reported and the outcome measure is not applicable as no ADA sample was positive. As no ADA, titer and subtype could not be identified
Amount of RO7234292 in Urine Ae (Micrograms) Up to 72 hours
Trial Locations
- Locations (3)
Centre For Human Drug Research; Research
š³š±Leiden, Netherlands
Leonard Wolfson Experimental Neurology Centre
š¬š§London, United Kingdom
Manchester University NHS Foundation Trust (MFT)
š¬š§Manchester, United Kingdom