An extension study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of the study drug, RO7234292 (ISIS 443139), in patients who participated in prior investigational studies of RO7234292

• Register: EUCTR
• Last refreshed on: 26 March 2024
• Main ID: EUCTR2017-002471-25-GB
• Date of registration: 04/08/2017
• Prospective Registration: Yes
• Primary sponsor: F.Hoffmann La-Roche Ltd
• Public title: An extension study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of the study drug, RO7234292 (ISIS 443139), in patients who participated in prior investigational studies of RO7234292
• Scientific title: AN OPEN-LABEL EXTENSION STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS AND PHARMACODYNAMICS OF RO7234292 (ISIS 443139) IN HUNTINGTON'S DISEASE PATIENTS WHO PARTICIPATED IN PRIOR INVESTIGATIONAL STUDIES OF RO7234292 (ISIS 443139)
• Date of first enrolment: 18/10/2018
• Target sample size: 46
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-002471-25
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Canada, Germany, United Kingdom

Contacts

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche LTD

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche LTD

Key inclusion & exclusion criteria

Inclusion criteria:
1. Must be capable of giving informed consent (in the opinion of the Investigator)
2. Must have completed the Treatment Period of Study ISIS 443139-CS1
3. Able and willing to meet all study requirements in the opinion of the Investigator,
4. Females must be non-pregnant, non-lactating
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 43
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 3

Exclusion criteria:
1. Treatment with an investigational drug (other than ISIS 443139 in Study ISIS 443139-CS1), biological agent, or device within 1 month of Screening, or 5 half-lives of investigational agent, whichever is longer. Concurrent or planned concurrent participation in any clinical study (including observational and non-interventional studies) without approval of the Sponsor Medical Monitor
2. Antiplatelet or anticoagulant therapy within the 14 days prior to first lumbar puncture in the study or anticipated use during the study, including but not limited to aspirin (unless = 81 mg/day), clopidogrel, dipyridamole, warfarin, dabigatran, rivaroxaban and apixaban
3. Prior treatment with an antisense oligonucleotide including siRNA (other than ISIS 443139 in Study ISIS 443139-CS1)
4. Presence of an implanted shunt for the drainage of CSF or an implanted CNS catheter
5. Clinically-relevant hematological, hepatic, cardiac or renal disease or event. Clinically-significant abnormal hepatic, renal or hematology lab
tests at Screening must be discussed with the Sponsor MedicalMonitor
6. Malignancy within 5 years of Screening, except for basal or squamouscell carcinoma of the skin or carcinoma in situ of the cervix that has
been successfully treated
7. Any condition that significantly increases risk of meningitis unlesspatient is receiving appropriate prophylactic treatment
8. History of bleeding diathesis or coagulopathy, platelet count < LLN unless stable and assessed by the Investigator and Sponsor Medical Monitor to be not clinically significant
9. Have any other condition which, in the opinion of the Investigator or Sponsor, would make the patient unsuitable for inclusion or could
interfere with the patient participating in or completing the study


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Early Manifest Huntington's Disease
MedDRA version: 20.0 Level: PT Classification code 10070668 Term: Huntington's disease System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Intervention(s)

Product Code: Ro 723-4292/F02
Pharmaceutical Form: Solution for injection
INN or Proposed INN: n.a.
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-

Primary Outcome(s)

Main Objective: To evaluate the safety and tolerability of monthly and bimonthly (every other month) intrathecal (IT) bolus administrations of RO7234292 to patients with Huntington's disease (HD).

Primary end point(s): There is no single primary endpoint for this study. Important endpoints that will be evaluated are listed below:
Safety and Tolerability Endpoints
- Columbia - Suicide Severity Rating Scale (C-SSRS)
- Physical examination and standard neurological assessment (including fundi)
- Pregnancy testing
- Vital signs (heart rate [HR], BP, orthostatic changes, weight)
? - ECG
? - AEs and concomitant medications
? - CSF safety labs (cell counts, protein, glucose)
? - Plasma laboratory tests (clinical chemistry, hematology)
? - Urinalysis
? -Safety neuroimaging assessments
.

Secondary Objective: To characterize the cerebrospinal fluid (CSF) pharmacokinetics of monthly and bimonthly IT doses of RO7234292. T
o explore effects of monthly and bimonthly IT doses of RO7234292 on key pharmacodynamic biomarkers and clinical endpoints relevant to HD, including:
• - Mutant huntingtin protein (mutant Htt) level in CSF
• - Structural MRI (ventricular, caudate and whole brain volumes)
•- Quantitative electroencephalography
• - Assessments of physical functioning, activities of daily living, gait, balance, mobility, and cognitive functioning

Timepoint(s) of evaluation of this end point: Continuous

Secondary Outcome(s)

Secondary end point(s): Pharmacokinetic Endpoints
Plasma C max, AUC, elimination half-life and trough and post-distribution drug levels will be assessed, where appropriate. CSF elimination half-life and trough drug levels will be assessed, where appropriate. Urinary excretion parameters such as amount of drug excreted and renal clearance will be determined, as appropriate.
Biochemical Endpoints: Mutant huntingtin protein (mutant Htt) level in CSF
Neuroimaging Endpoints: Structural MRI (ventricular, caudate and whole brain volumes)
Electrophysiological Endpoints: Quantitative electroencephalography
Clinical Endpoints: Assessments of physical functioning, activities of daily living, gait, balance, mobility, and cognitive functioning

Timepoint(s) of evaluation of this end point: CSF is collected periodically during the study (prior to each RO7234292 dose and once each during screening and follow-up). Imaging, EEG and cognitive data are collected approximately every 6 months. Functional data, such as gait and ADL, are collected throughout the study using handheld devices.

Secondary ID(s)

BN40697(ISIS443139-CS2)

Source(s) of Monetary Support

F.Hoffmann La-Roche Ltd - Basel

Ethics review

Status: Approved
Approval date: 03/10/2017
Contact:

Results

• Results available: Yes
• Date Posted: 13/11/2020
• Date Completed: 08/10/2019
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-002471-25/results