Skip to main content
OpenTrials
Completed

NCT Number: 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

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).

Completed

Looking for future studies?

Notify Me

Key information

Age range

25 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Centre For Human Drug Research; Research, Leiden, Netherlands

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

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.

Other names: Tominersen

Primary outcomes

  1. Concentrations of RO7234292 in CSF (Cerebrospinal Fluid)

    Time frame: Day 1, 2, 3, 4, 29, 43, 71, 127, and follow-up visit (6 months after last study drug administration)

    NA represents: insufficient number of participants with events.

  2. Concentrations of RO7234292 in Plasma

    Time frame: Day 1, 2, 3, 4, 5, 28, 29, 30, 43, 71, 127, and follow-up visit (6 months after last study drug administration)

    NA represents:insufficient number of participants with events

  3. mHTT (Mutant Huntingtin) Concentration in CSF

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

    CSF Mutant Huntingtin Protein (fmol/L) values at time point visits are reported.

Secondary outcomes

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

    Time frame: Up to 6 months

    Severity levels levels: 1 = mild; 2 = moderate; 3 = severe used according to NCI-CTCAE grading system.

    Percentage of participants with 1-3 levels of severities are reported.

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

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

    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. Scores 1-10 is used, 1 being less and to 10 being severity increasing.

    Only one time frame was used per score category: from screening to follow-up visit.

  3. Incidence of Anti-Drug Antibodies (ADAs)

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

    Percentage of participants who have negative or positive anti-drug antibody affects are reported.

  4. Titer and Antibody Subtype, Determined if ADAs Are Identified

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

    The data cannot be reported and the outcome measure is not applicable as no ADA sample was positive. As no ADA, titer and subtype could not be identified

  5. Amount of RO7234292 in Urine Ae (Micrograms)

    Time frame: Up to 72 hours

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Registry information

Official study 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

Important dates

Study start
2019
Primary completion
2022
Study completion
2022
First posted
Jun 27, 2019
Registry last updated
Oct 3, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.