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

NCT ID: NCT04000594

Last Updated: 2024-10-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-02
• Study Completion Date: 2022-01-18

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).

Conditions

Huntingtons Disease

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dose level 1 of RO7234292 (RG6042)

Participants will receive dose level 1 of RO7234292 (RG6042) intrathecally on Day 1 and Day 29.

Group Type: EXPERIMENTAL

RO7234292 (RG6042)

Intervention Type: DRUG

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.

Dose level 2 of RO7234292 (RG6042)

Participants will receive dose level 2 of RO7234292 (RG6042) intrathecally on Day 1 and Day 29.

Group Type: EXPERIMENTAL

RO7234292 (RG6042)

Intervention Type: DRUG

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.

Dose level 3 of RO7234292 (RG6042)

Participants will receive dose level 3 of RO7234292 (RG6042) intrathecally on Day 1 and Day 29.

Group Type: EXPERIMENTAL

RO7234292 (RG6042)

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Tominersen

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.

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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

Countries

Netherlands; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

GEN-PEAK

Identifier Type: OTHER

Identifier Source: secondary_id

BP40410

Identifier Type: -

Identifier Source: org_study_id