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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04000594
Recruitment Status : Recruiting
First Posted : June 27, 2019
Last Update Posted : May 20, 2020
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

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).

Condition or disease Intervention/treatment Phase
Huntingtons Disease Drug: RO7234292 (RG6042) Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : September 2, 2019
Estimated Primary Completion Date : January 22, 2021
Estimated Study Completion Date : January 22, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Dose level 1 of RO7234292 (RG6042)
Participants will receive dose level 1 of RO7234292 (RG6042) intrathecally on Day 1 and Day 29.
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.
Other Name: Tominersen

Experimental: Dose level 2 of RO7234292 (RG6042)
Participants will receive dose level 2 of RO7234292 (RG6042) intrathecally on Day 1 and Day 29.
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.
Other Name: Tominersen

Experimental: Dose level 3 of RO7234292 (RG6042)
Participants will receive dose level 3 of RO7234292 (RG6042) intrathecally on Day 1 and Day 29.
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.
Other Name: Tominersen




Primary Outcome Measures :
  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) ]
  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) ]
  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) ]

Secondary Outcome Measures :
  1. Incidence and Severity of Adverse Events [ Time Frame: Up to 6 months ]
  2. Percentage of Participants With Suicidal Ideation or Behavior, as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score [ Time Frame: Screening, Day -1, Day 28, Day 71, Day 127, and follow-up visit (6 months after last study drug administration) ]

    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.


  3. Incidence of Anti-Drug Antibodies (ADAs) [ Time Frame: Day 1, Day 28, and follow-up visit (6 months after last study drug administration) ]
  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) ]
  5. Concentrations of RO7234292 in Urine [ Time Frame: Up to 72 hours ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   25 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04000594


Contacts
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Contact: Reference Study ID Number: BP40410 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

Locations
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Netherlands
Centre For Human Drug Research; Research Recruiting
Leiden, Netherlands, 2333
United Kingdom
Leonard Wolfson Experimental Neurology Centre Recruiting
London, United Kingdom, WC1N 3BG
Manchester University NHS Foundation Truct (MFT) Recruiting
Manchester, United Kingdom, M13 9WL
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche

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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT04000594    
Other Study ID Numbers: BP40410
GEN-PEAK ( Other Identifier: Hoffmann-La Roche )
First Posted: June 27, 2019    Key Record Dates
Last Update Posted: May 20, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
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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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Huntington Disease
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Dementia
Chorea
Dyskinesias
Movement Disorders
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Cognition Disorders
Neurocognitive Disorders
Mental Disorders