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

Huntingtons Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04000594
• Other study ID #: BP40410
• Secondary ID: GEN-PEAK
• Status: Completed
• Phase: Phase 1
• Start date: September 2, 2019
• Est. completion date: January 18, 2022

Study information

• Verified date: May 2022
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: January 18, 2022
• Est. primary completion date: January 18, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Huntington Disease
• 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.

Locations

Country	Name	City	State
Netherlands	Centre For Human Drug Research; Research	Leiden
United Kingdom	Leonard Wolfson Experimental Neurology Centre	London
United Kingdom	Manchester University NHS Foundation Trust (MFT)	Manchester

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Secondary	Incidence and Severity of Adverse Events		Up to 6 months
Secondary	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.	Screening, Day -1, Day 28, Day 71, Day 127, and follow-up visit (6 months after last study drug administration)
Secondary	Incidence of Anti-Drug Antibodies (ADAs)		Day 1, Day 28, and follow-up visit (6 months after last study drug administration)
Secondary	Titer and Antibody Subtype, determined if ADAs are Identified		Day 1, Day 28, and follow-up visit (6 months after last study drug administration)
Secondary	Concentrations of RO7234292 in Urine		Up to 72 hours