A RANDOMIZED, MULTICENTER, DOUBLE-BLIND, PLACEBO-CONTROLLED, PHASE III CLINICAL STUDY TO EVALUATE THE EFFICACY AND SAFETY OF INTRATHECALLY ADMINISTERED RO7234292 (RG6042) IN PATIENTS WITH MANIFEST HUNTINGTON'S DISEASE
- Conditions
- Huntington's chorea10028037Huntington's disease
- Registration Number
- NL-OMON55873
- Lead Sponsor
- Roche Nederland B.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 20
* Signed Informed Consent Form
* Age 25 to 65 years, inclusive
* Manifest HD diagnosis, defined as a diagnostic confidence level (DCL) score
of 4
* Independence Scale (IS) score * 70
* Genetically confirmed disease by direct DNA testing with a CAP score >400,
calculated as follows: CAP <= 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
o Long-distance (e.g., > 50 meters) use of wheelchairs for convenience or
transfer is permitted.
* Body mass index 16-32 kg/m2; total body weight > 40 kg
* Ability to undergo and tolerate MRI scans, 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
* Ability and willingness, in the investigator's judgment, 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
criteria as specified in protocol section 4.1.1.
* For women of childbearing potential: agreement to remain abstinent (refrain
from heterosexual intercourse) or use contraceptive measures, as defined in
protocol section 4.1.1.
* For men: agreement to remain abstinent (refrain from heterosexual
intercourse) or use a condom, and agreement to refrain from donating sperm, as
defined in protocol section 4.1.1.
* History of attempted suicide or suicidal ideation with plan that required
hospital visit and/or change in level of care within 12 months prior to
screening
* Current suicidal ideation is demonstrated by the C-SSRS per judgment of the
investigator. If suicidal ideation is present, a risk assessment should be done
by an appropriately qualified mental health professional to assess whether it
is safe for the patient to participate in the study.
* 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
* Women of childbearing potential must have a negative serum pregnancy test
result at baseline and a confirmatory urine pregnancy test prior to initiation
of study drug.
* Presence of an implanted shunt for the drainage of CSF or an implanted CNS
catheter
* Positive for hepatitis C virus (HCV) antibody or hepatitis B surface antigen
(HBsAg) at screening
* Known HIV infection
* Current or previous use of an antisense oligonucleotide (including small
interfering RNA)
* Current or previous use of anti-psychotics prescribed for a primary
independent psychotic disorder (i.e., schizophrenia, schizoaffective disorder,
bipolar disorder type I, severe with psychotic features), cholinesterase
inhibitors, memantine, amantadine, or riluzole within 12 weeks from initiation
of study treatment
* Current use of antipsychotics for motor symptoms or mood stabilization (i.e.,
irritability or aggressive behavior) 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 (e.g., coenzyme Q10, vitamins, creatine) 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
(unless * 81 mg/day), clopidogrel, dipyridamole, warfarin, dabigatran,
rivaroxaban, and apixaban
* History of bleeding diathesis or coagulopathy
* Platelet count less than the lower limit of normal
* Platelet counts between 125,000 and 150,000 mm3 are permissible as long as
the investigator confi
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Efficacy: change from baseline in the composite Unified Huntington's Disease<br /><br>Rating Scale (cUHDRS) score at Week 101.<br /><br>Biomarker: change from baseline in CSF mHTT protein level at Week 101.</p><br>
- Secondary Outcome Measures
Name Time Method