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).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
12
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.
Centre For Human Drug Research; Research
Leiden, Netherlands
Leonard Wolfson Experimental Neurology Centre
London, United Kingdom
Manchester University NHS Foundation Trust (MFT)
Manchester, United Kingdom
Concentrations of RO7234292 in CSF (Cerebrospinal Fluid)
NA represents: insufficient number of participants with events.
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
NA represents:insufficient number of participants with events
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
CSF Mutant Huntingtin Protein (fmol/L) values at time point visits are reported.
Time frame: Days 1, 2, 3, 29, 43, 71, 127 and follow-up visit (6 months after last study drug administration)
Percentage of Participants With Adverse Events According to NCI-CTCAE Grading System
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.
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
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.
Time frame: From Screening Day Up To Follow-up Visit (6 months after the last Dosing Day-Day 127)
Incidence of Anti-Drug Antibodies (ADAs)
Percentage of participants who have negative or positive anti-drug antibody affects are reported.
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
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
Time frame: Day 1, Day 28, and follow-up visit (6 months after last study drug administration)
Amount of RO7234292 in Urine Ae (Micrograms)
Time frame: Up to 72 hours
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