Phase 1
Completed N=12
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
Source: ClinicalTrials.gov NCT04000594 ↗Enrolled (actual)
12
Serious AEs
16.7%
Results posted
Oct 2024
Primary outcomePrimary: Concentrations of RO7234292 in CSF (Cerebrospinal Fluid) — 197000; 372000; 933000; 6220 ng/mL
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).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Concentrations of RO7234292 in CSF (Cerebrospinal Fluid) |
197000; 372000; 933000; 6220; 30200; 41100 | — |
| PRIMARY Concentrations of RO7234292 in Plasma |
209; 709; 941; 30.5; 709; 104 | — |
| PRIMARY mHTT (Mutant Huntingtin) Concentration in CSF |
177.78; 130.35; 99.02; 204.39; 81.74; 127.39 | — |
| SECONDARY Percentage of Participants With Adverse Events According to NCI-CTCAE Grading System |
50; 0; 50.0; 25; 75; 25.0 | — |
| SECONDARY Percentage of Participants With Suicidal Ideation or Behavior, as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score |
0; 25; 0; 0; 0; 0 | — |
| SECONDARY Incidence of Anti-Drug Antibodies (ADAs) |
100; 100; 100; 100; 100; 100 | — |
| SECONDARY Titer and Antibody Subtype, Determined if ADAs Are Identified |
— | — |
| SECONDARY Amount of RO7234292 in Urine Ae (Micrograms) |
236.0; 207.0; 1650.0 | — |
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.
Data sourced from ClinicalTrials.gov (NCT04000594). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.