Clinical trial NCT04000594: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Huntingtons Disease
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2019-06-27
Enrollment: 12
Sex: ALL
Minimum age (years): 25
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
measure: Concentrations of RO7234292 in CSF (Cerebrospinal Fluid)
timeFrame: Day 1, 2, 3, 4, 29, 43, 71, 127, and follow-up visit (6 months after last study drug administration)
measure: Concentrations of RO7234292 in Plasma
timeFrame: Day 1, 2, 3, 4, 5, 28, 29, 30, 43, 71, 127, and follow-up visit (6 months after last study drug administration)
measure: mHTT (Mutant Huntingtin) Concentration in CSF
timeFrame: Days 1, 2, 3, 29, 43, 71, 127 and follow-up visit (6 months after last study drug administration)
Secondary outcomes:
measure: Percentage of Participants With Adverse Events According to NCI-CTCAE Grading System
timeFrame: Up to 6 months
measure: Percentage of Participants With Suicidal Ideation or Behavior, as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score
timeFrame: From Screening Day Up To Follow-up Visit (6 months after the last Dosing Day-Day 127)
measure: Incidence of Anti-Drug Antibodies (ADAs)
timeFrame: Day 1, Day 28, and follow-up visit (6 months after last study drug administration)
measure: Titer and Antibody Subtype, Determined if ADAs Are Identified
timeFrame: Day 1, Day 28, and follow-up visit (6 months after last study drug administration)
measure: Amount of RO7234292 in Urine Ae (Micrograms)
timeFrame: Up to 72 hours
Other outcomes:
Locations:
city: Leiden
country: Netherlands
facility: Centre For Human Drug Research; Research
city: London
country: United Kingdom
facility: Leonard Wolfson Experimental Neurology Centre
city: Manchester
country: United Kingdom
facility: Manchester University NHS Foundation Trust (MFT)
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: