A Study to Evaluate the Efficacy and Safety of Intrathecally Administered RO7234292 (RG6042) in Patients with Manifest Huntington's disease
- Conditions
- Huntington's disease (HD)MedDRA version: 20.0Level: PTClassification code 10070668Term: Huntington's diseaseSystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
- Registration Number
- EUCTR2018-002987-14-PL
- Lead Sponsor
- F.Hoffmann La-Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 801
- 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 < 1% per year, during the treatment period and for 5
months after the final dose of study drug
- For men: agreement to remain abstinent or use a condom, and
agreement to refrain from donating sperm, with a female partner of
childbearing potential or pregnant female partner, men must remain
abstinent or use a condom during the treatment period and for 5 months
after the final dose of study drug to avoid exposing the Embryo
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 753
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 47
- History of attempted suicide or suicidal ideation with plan (i.e., active suididal 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 drugelimination 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
squamous cell carcinoma of the skin or carcinoma in situ of the cervix
that
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method