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

NCT04000594 | Completed Phase 1 Results

• 2 other identifiers: BP40410GEN-PEAK
• Study Type: interventional
• Target: 12
• Locations: 2 countries
• Sites: 3

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

Outcome Measures

Primary Outcomes (3)

• Concentrations of RO7234292 in CSF (Cerebrospinal Fluid)

  NA represents: insufficient number of participants with events.

  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

  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.

  Days 1, 2, 3, 29, 43, 71, 127 and follow-up visit (6 months after last study drug administration)

Secondary Outcomes (5)

• Percentage of Participants With Adverse Events According to NCI-CTCAE Grading System

  Up to 6 months

• Percentage of Participants With Suicidal Ideation or Behavior, as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score

  From Screening Day Up To Follow-up Visit (6 months after the last Dosing Day-Day 127)

• Incidence of Anti-Drug Antibodies (ADAs)

  Day 1, Day 28, and follow-up visit (6 months after last study drug administration)

• Titer and Antibody Subtype, Determined if ADAs Are Identified

  Day 1, Day 28, and follow-up visit (6 months after last study drug administration)

• Amount of RO7234292 in Urine Ae (Micrograms)

  Up to 72 hours

Study Arms (3)

Dose level 1 of RO7234292 (RG6042)

EXPERIMENTAL

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

Drug: RO7234292 (RG6042)

Dose level 2 of RO7234292 (RG6042)

EXPERIMENTAL

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

Drug: RO7234292 (RG6042)

Dose level 3 of RO7234292 (RG6042)

EXPERIMENTAL

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

Drug: RO7234292 (RG6042)

Interventions

RO7234292 (RG6042) 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.

Also known as: Tominersen

Dose level 1 of RO7234292 (RG6042); Dose level 2 of RO7234292 (RG6042); Dose level 3 of RO7234292 (RG6042)

Eligibility Criteria

• Age: 25 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (3)

Centre For Human Drug Research; Research

Leiden, 2333, Netherlands

Location

Leonard Wolfson Experimental Neurology Centre

London, WC1N 3BG, United Kingdom

Location

Manchester University NHS Foundation Trust (MFT)

Manchester, M13 9WL, United Kingdom

Location

MeSH Terms

Conditions

Chorea

Interventions

tominersen

Condition Hierarchy (Ancestors)

Dyskinesias; Movement Disorders; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2019
• First Posted: June 27, 2019
• Study Start: September 2, 2019
• Primary Completion: January 18, 2022
• Study Completion: January 18, 2022
• Last Updated: October 3, 2024
• Results First Posted: October 3, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1); GB (2)