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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

Primary Purpose

Huntingtons Disease

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

RO7234292 (RG6042)

About this trial

This is an interventional treatment trial for Huntingtons Disease

Eligibility Criteria

25 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Centre For Human Drug Research; Research
Leonard Wolfson Experimental Neurology Centre
Manchester University NHS Foundation Trust (MFT)

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Dose level 1 of RO7234292 (RG6042)

Dose level 2 of RO7234292 (RG6042)

Dose level 3 of RO7234292 (RG6042)

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

Concentrations of RO7234292 in CSF (cerebrospinal fluid)

Concentrations of RO7234292 in Plasma

mHTT (mutant Huntingtin) Concentration in CSF

Secondary Outcome Measures

Incidence and Severity of Adverse Events

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.

Incidence of Anti-Drug Antibodies (ADAs)

Titer and Antibody Subtype, determined if ADAs are Identified

Concentrations of RO7234292 in Urine

Full Information

NCT ID

NCT04000594

First Posted

June 26, 2019

Last Updated

May 25, 2022

Sponsor

Hoffmann-La Roche

1. Study Identification

Unique Protocol Identification Number

NCT04000594

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2022

Overall Recruitment Status

Completed

Study Start Date

September 2, 2019 (Actual)

Primary Completion Date

January 18, 2022 (Actual)

Study Completion Date

January 18, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hoffmann-La Roche

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Huntingtons Disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

12 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Dose level 1 of RO7234292 (RG6042)

Arm Type

Experimental

Arm Description

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

Arm Title

Dose level 2 of RO7234292 (RG6042)

Arm Type

Experimental

Arm Description

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

Arm Title

Dose level 3 of RO7234292 (RG6042)

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

RO7234292 (RG6042)

Other Intervention Name(s)

Tominersen

Intervention Description

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.

Primary Outcome Measure Information:

Title

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)

Title

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)

Title

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)

Secondary Outcome Measure Information:

Title

Incidence and Severity of Adverse Events

Time Frame

Up to 6 months

Title

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

Description

Time Frame

Screening, Day -1, Day 28, Day 71, Day 127, and follow-up visit (6 months after last study drug administration)

Title

Incidence of Anti-Drug Antibodies (ADAs)

Time Frame

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

Title

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)

Title

Concentrations of RO7234292 in Urine

Time Frame

Up to 72 hours

10. Eligibility

Sex

All

Minimum Age & Unit of Time

25 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Trials

Organizational Affiliation

Hoffmann-La Roche

Official's Role

Study Director

Facility Information:

Facility Name

Centre For Human Drug Research; Research

City

Leiden

ZIP/Postal Code

2333

Country

Netherlands

Facility Name

Leonard Wolfson Experimental Neurology Centre

City

London

ZIP/Postal Code

WC1N 3BG

Country

United Kingdom

Facility Name

Manchester University NHS Foundation Trust (MFT)

City

Manchester

ZIP/Postal Code

M13 9WL

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on Sharing of Clinical Study Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

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