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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: EUCTR
Last refreshed on: 16 May 2022
Main ID:  EUCTR2018-002987-14-PL
Date of registration: 07/04/2020
Prospective Registration: No
Primary sponsor: F.Hoffmann La-Roche Ltd
Public title: A Study to Evaluate the Efficacy and Safety of Intrathecally Administered RO7234292 (RG6042) in Patients with Manifest Huntington's disease
Scientific title: 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
Date of first enrolment: 19/03/2019
Target sample size: 801
Recruitment status: Not Recruiting
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-002987-14
Study type:  Interventional clinical trial of medicinal product
Study design:  Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3  
Phase:  Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no
Countries of recruitment
Argentina Australia Austria Canada China Denmark France Germany
Italy Japan Netherlands New Zealand Poland Russian Federation Spain Switzerland
United Kingdom United States
Contacts
Name: Trial Information Support Line-TISL   
Address:  Grenzacherstrasse 124 4070 Basel Switzerland
Telephone:
Email: global.rochegenentechtrials@roche.com
Affiliation:  F. Hoffmann-La Roche LTD
Name: Trial Information Support Line-TISL   
Address:  Grenzacherstrasse 124 4070 Basel Switzerland
Telephone:
Email: global.rochegenentechtrials@roche.com
Affiliation:  F. Hoffmann-La Roche LTD
Key inclusion & exclusion 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 < 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

Exclusion criteria:
- 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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
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
Intervention(s)

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, formerly ISIS 443139, IONIS-HTTRx
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 6-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intrathecal use

Primary Outcome(s)
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
Timepoint(s) of evaluation of this end point: 1-3. Baseline (Week 1) and Week 101
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
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
Secondary Outcome(s)
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
termination
15-16Baseline, Week 13, 21, 37, 53, 69, 85, 101 and at early treatment
termination, safety follow up visit
17-18. Baseline and Week 101

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
Secondary ID(s)
BN40423
NCT03761849
2018-002987-14-GB
Source(s) of Monetary Support
F.Hoffmann La-Roche Ltd - Basel
Secondary Sponsor(s)
Ethics review
Status: Approved
Approval date: 26/02/2019
Contact:
Results
Results available:
Date Posted:
Date Completed:
URL:
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