Huntington's disease (HD) MedDRA version: 20.0 Level: PT Classification code 10070668 Term: Huntington's disease System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Code: Ro 723-4292/F02
Pharmaceutical Form: Solution for injection
INN or Proposed INN: not available
CAS Number: 1709886-74-7
Current Sponsor code: RO7234292
Other descriptive name: RG6042, fo
Sponsors
F.Hoffmann La-Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age 25 to 65 years at the time of first dose administration - Manifest HD diagnosis (defined as DCL score of 4) - Independence Scale (IS) score >= 70 - Genetically confirmed disease by direct DNA testing with a CAP score > 400 (Age x [CAG repeat length – 33.66]) - Ability to read the words "red," "blue," and "green" in native language - Ability to walk unassisted without a cane or walker and move about without a wheelchair on a daily basis as determined at screening and baseline visit - Body mass index 16-32 kg/m2; total body weight > 40 kg - Ability to undergo and tolerate magnetic resonance imaging (MRI) scans - Ability to tolerate blood draws and lumbar punctures - Creatinine Clearance (CrCl) >= 60 mL/min (Cockcroft Gault formula) - Ability and willingness, in the investigator's judgment, to comply with all aspects of the protocol including completion of interviews and questionnaires for the duration of the study and to carry a smartphone, wear a digital monitoring device, and complete smartphone-based tasks - Stable medical, psychiatric, and neurological status for at least 12 weeks prior to screening and at the time of enrollment - Signed study companion consent for participation who fulfills all of the following criteria: o Age >= 18 years o Reliable and competent, in the investigator's judgment o Sufficiently knowledgeable of the patient's condition to complete study companion assessments of the patient, and likely to remain sufficiently knowledgeable throughout the study, in the investigator's judgment o Able to comment on study participant's symptoms and functioning experience o Able and willing to attend in person all clinical visits for completion of companion assessments and for input into the clinician-rated TFC scale o Companions must have no cognitive, behavioral or motor change, in the opinion of the investigator, that would question the validity of the acquired observer-reported data - For women of childbearing potential: agreement to remain abstinent or use contraceptive measures, women must remain abstinent or use two methods of contraception, including at least one method with a failure rate of =65 years) yes F.1.3.1 Number of subjects for this age range 47
Exclusion criteria
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, or vital sign abnormality or claustrophobia at screening that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study - History known to the investigator or presence of an abnormal ECG that is clinically significant in the investigator's opinion, including complete left bundle branch block, second- or third-degree atrioventricular heart block, or evidence of prior myocardial infarction - Lifetime clinical diagnosis of chronic migraines - Pregnant or breastfeeding, or intending to become pregnant during the study or within 5 months after the final dose of study drug - Presence of an implanted shunt for the drainage of CSF or an implanted central nervous system catheter - Positive for hepatitis C virus or hepatitis B surface antigen at screening - Known HIV infection - Current or previous use of an antisense oligonucleotide - Current or previous use of anti-psychotics prescribed for a primary independent psychotic disorder, cholinesterase inhibitors, memantine, amantadine, or riluzole within 12 weeks from initiation of study treatment - Current use of antipsychotics for motor symptoms or mood stabilization and/or tetrabenazine, valbenazine, or deutetrabenazine at a dose that has not been stable for at least 12 weeks prior to screening or is anticipated to change between screening and treatment initiation - Current use of supplements at a dose that has not been stable for at least 6 weeks prior to screening or is anticipated to change during the study - Current use of an antidepressant or benzodiazepine at a dose that has not been stable for at least 12 weeks prior to screening or is anticipated to change between screening and treatment initiation - Treatment with investigational therapy within 4 weeks or 5 drug-elimination half-lives prior to screening, whichever is longer - Antiplatelet or anticoagulant therapy within 14 days prior to screening or anticipated use during the study, including, but not limited to, aspirin, clopidogrel, dipyridamole, warfarin, dabigatran, rivaroxaban, and apixaban - History of bleeding diathesis or coagulopathy - Platelet count less than the lower limit of normal - History of gene therapy, cell transplantation, or any experimental brain surgery - Concurrent or planned participation in any interventional clinical study, including explicit pharmacological and non-pharmacological interventions - Drug and/or alcohol abuse or psychological or physiological dependency within 12 months prior to screening, as per the investigator's judgment - Poor peripheral venous access - Scoliosis or spinal deformity or surgery making IT injection not feasible in an outpatient setting and potentially interfering with distribution of RO7234292 up the neuraxis - An infection requiring oral or IV antibiotics within 14 days prior to screening and prior to randomization - Antiretroviral medications, including antiretroviral medication taken as prophylaxis within 12 months of study enrollment - Malignancy within 5 years prior to screening, except basal or squamo
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To evaluate the efficacy of RO7234292 from baseline compared with placebo on the basis of composite Unified Huntington's Disease Rating Scale (cUHDRS) and total functional capacity scale (TFC) [only for US FDA] score at Week 101 • To evaluate the effects of RO7234292 from baseline compared with placebo on the basis of cerebrospinal fluid (CSF) mutant huntingtin (mHTT) protein level at Week 101;Secondary Objective: •To evaluate the efficacy of RO7234292 from baseline compared with placebo on basis of cUHDRS [only for US FDA] TFC, total Motor Score (TMS), symbol digit modalities test (SDMT), stroop word reading test (SWR), clinical global impression, severity scale (CGI-S) score at Week 101 •To evaluate the safety and tolerability of RO7234292 compared with placebo on basis of adverse events, Montreal cognitive assessment (MoCA), vital signs, electrocardiograms parameters, clinical laboratory results and by Columbia-suicide severity rating scale (C-SSRS) score •To characterize the RO7234292 PK profile in plasma and trough CSF on basis of concentration of RO7234292 in plasma and trough concentration of RO7234292 in CSF at specified timepoints •To evaluate the immune response to RO7234292 on basis of Incidence of anti-drug antibodies •To evaluate the effects of RO7234292 compared with placebo on the basis of whole and regional brain volumes,CSF neurofilament light chain (NfL) protein Level;Primary end point(s): 1. Change from baseline in the cUHDRS score at Week 101 2. Change from baseline in the TFC score at Week 101 (For US FDA) 3. Change from baseline in CSF mHTT protein level at Week 101;Timepoint(s) of evaluation of this end point: 1-3. Baseline (Week 1) and Week 101 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Change from baseline in the cUHDRS score at Week 101 (For US FDA) 2. Change from baseline in scores for TFC at Week 101 3. Change from baseline in scores for TMS at Week 101 4. Change from baseline in scores for SDMT at Week 101 5. Change from baseline in scores for SWR at Week 101 6. Change from baseline in the CGI-S score at Week 101 7. Proportion of patients with a decrease from baseline of >= 1 point on the TFC at Week 101 8. Proportion of patients with a decline from baseline of >= 1.2 points on the cUHDRS at Week 101 9. Proportion of patients with an unchanged or improved score on the CGI-C score from baseline at Week 101 10. Incidence and severity of adverse events, with severity determined according to the Adverse Event Severity Grading Scale 11. Change from baseline in MoCA 12. Change from baseline in vital signs, electrocardiograms parameters, and clinical laboratory results 13. Proportion of patients with suicidal ideation or behavior, as assessed by C-SSRS score at each visit, including detailed focus on any individual cases identified as having severe ideation or behavior during the study conduct 14. CSF and plasma concentration of RO7234292 15. Incidence of anti-drug antibodies (ADAs) at specified timepoints relative to the prevalence of ADAs at baseline 16. Titer and antibody subtype, determined if ADAs are identified 17. Change from baseline in whole and regional brain volumes (caudate, whole brain, and ventricular), as determined by structural MRI, at Week 101 18. Change from baseline in CSF NfL protein level at Week 101;Timepoint(s) of evaluation of this end point: 1-9. Baseline and Week 101 10. Up to 101 weeks (25 Months) 11. Baseline, Week 5, 21, 37, 53, 69, 85, 101 12. Baseline to 101 weeks 13. At screening (Week ?4 to ?1), baseline, Week 5-101, end of treatment for early treatment termination and at early treatment termination 14. Baseline, Week 13, 21, 37, 53, 69, 85, 101 and at early treatment | — |
Countries
Argentina, Australia, Austria, Canada, Chile, China, Denmark, France, Germany, Italy, Japan, Netherlands, New Zealand, Poland, Russian Federation, Spain, Switzerland, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche LTD
Outcome results
None listed