Efficacy and safety of remibrutinib compared to teriflunomide in participants with relapsing multiple sclerosis, followed by long term treatment with remibrutinib

• Register: EUCTR
• Last refreshed on: 2 March 2022
• Main ID: EUCTR2020-005899-36-ES
• Date of registration: 29/12/2021
• Prospective Registration: Yes
• Primary sponsor: Novartis Farmacéutica S.A.
• Public title: Efficacy and safety of remibrutinib compared to teriflunomide in participants with relapsing multiple sclerosis, followed by long term treatment with remibrutinib
• Scientific title: A randomized, double-blind, double-dummy, parallel-group study, comparing the efficacy and safety of remibrutinib versus teriflunomide in participants with relapsing multiple sclerosis, followed by extended treatment with open-label remibrutinib
• Date of first enrolment: 11/02/2022
• Target sample size: 800
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-005899-36
• 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: yes; Other trial design description: Double-dummy; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Slovakia, Spain

Contacts

• Name: Trial Monitoring Organization (TMO)
• Affiliation: Novartis Farmacéutica S.A.

• Name: Trial Monitoring Organization (TMO)
• Affiliation: Novartis Farmacéutica S.A.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Signed informed consent obtained prior to any assessment performed (confirm at screening visit)
2. Male or female participants 18 to 55 years of age (inclusive) at screening
3. Diagnosis of RMS according to the 2017 McDonald diagnostic criteria
(this would include relapsing-remitting course (RRMS) or secondary progressive (SPMS) course with disease activity) as confirmed at screening visit.
4. At least: 1 documented relapse within the previous year, OR 2 documented relapses within the previous 2 years, prior to screening, OR 1 active Gadolinium (Gd)-enhancing lesion in the 12 months prior to screening
5. EDSS score of 0 to 5.5 (inclusive) at screening and randomization
6. Neurologically stable within 1 month prior to screening and randomization (including no MS relapse in this period)
Please see protocol for complete detailed list of inclusion criteria
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 800
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Diagnosis of primary progressive multiple sclerosis (PPMS) according to the 2017 revision of the McDonald diagnostic criteria (Thompson et al 2018) at screening
2. Disease duration of more than 10 years in participants with EDSS score of 2 or less at screening
3. History of clinically significant CNS disease (e.g. stroke, traumatic brain or spinal injury, history or presence of myelopathy) or neurological disorders which may mimic MS at screening
4. Ongoing substance abuse (drug or alcohol) or any other factor (e.g. serious psychiatric condition) that may interfere with the participant's ability to cooperate and comply with the study procedures prior to randomization
5. History of malignancy of any organ system (other than complete resection of localized basal cell carcinoma of the skin or in situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases, at screening
6. Participants with history of confirmed Progressive Multifocal Leukoencephalopathy (PML) or Neurological symptoms consistent with PML prior to randomization
7. Women of child bearing potential unless they are using highly effective methods of contraception while taking study treatment and for at least 4 weeks after stopping study medication
8. Sexually active males, unless they agree to use a condom while taking study treatment and for at least 4 weeks after stopping double blind study medication

Please see protocol for complete detailed list of exclusion criteria


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

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Multiple Sclerosis
MedDRA version: 21.0 Level: PT Classification code 10080700 Term: Relapsing multiple sclerosis System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Product Name: remibrutinib
Product Code: LOU064
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Remibrutinib
Current Sponsor code: LOU064C
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Aubagio
Product Name: Teriflunomide
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Teriflunomide
CAS Number: 108605-62-5
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 14-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: Core part:
Demonstrate that remibrutinib is superior to teriflunomide in reducing the frequency of confirmed relapses
Extension part:
To assess long-term safety, tolerability and efficacy parameters in participants treated with remibrutinib

Secondary Objective: Core
Assess whether remibrutinib is superior to teriflunomide in
- Delaying disability progression based on the pooled data from both identical pivotal studies
- Reducing new inflammatory activity on MRI, based on MRI cohort data
- Reducing neuronal damage
- Disease-Activity-free status based on pooled data from both identical pivotal studies (MRI Cohort)
Extension (exploratory)
- Explore effect of remibrutinib versus terifunomide on brain MRI, relationship between remibrutinib exposure (PK) and efficacy and safety endpoints and relationship between potential biomarkers and their relationship with disease activity, disease course and treatment response
- Perform exploratory pharmacogenetic analysis based on blood samples for DNA (optional)
- Explore the effect of remibrutinib versus teriflunomide on disease activity free status and effect of remibrutinib versus teriflunomide on disability progression independent of relapse activity
See protocol for complete list of objectives

Primary end point(s): Core part:
Annualized relapse rate (ARR) of confirmed relapses
Extension Part:
- Adverse events, laboratory data, vital signs, electrocardiogram (ECG), Columbia Suicide Severity Rating
- ARR, number of new or enlarging T2 lesions on MRI per year (annualized T2 lesion rate), time to 6mCDP (EDSS), change in SDMT, NfL, Patient Reported Outcomes scores

Timepoint(s) of evaluation of this end point: Up to 30 months

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Up to 30 months

Secondary end point(s): Core part:
- Time to 3-month confirmed disability progression (3mCDP) on Expanded Disability Status Scale (EDSS)
- Time to 6-month confirmed disability progression (6mCDP) on EDSS
- Number of new or enlarging T2 lesions on MRI per year (annualized T2 lesion rate)
- Total number of Gd-enhancing T1 lesions per MRI scan
- Neurofilament light chain (NfL) concentration in serum
- Percentage of participants with No Evidence of Disease Activity-3 (NEDA-3), as assessed by absence of confirmed MS relapses, 6mCDP and new/enlarging T2 lesions on MRI

Extension part (exploratory)
- Annualized rate of brain volume loss (BVL), based on percentage brain volume change from baseline
- Change from baseline in cortical grey matter volume, hemispheric white matter volume and thalamus volume
- Slowly Expanding Lesions (SEL) in MRI
- T2 lesions, ARR, 3mCDP, safety endpoints etc. (as applicable)
- NfL, GFAP, total IgG, total IgM, B-cells, T2 lesions, ARR, 3mCDP etc. (as applicable)
- Evaluate the relationship of genetic polymorphisms data with drug metabolism, the indication, the drug target pathway, and treatment response
- Percentage of participants with NEDA-4, as assessed by the absence of confirmed MS relapses, 6mCDP, new/enlarging T2 lesions on MRI and brain volume loss > -0.4%/year
- Time to 3mCDP, 6mCDP

Secondary ID(s)

2020-005899-36-SK

CLOU064C12301

Source(s) of Monetary Support

Novartis Pharma AG

Ethics review

Status: Approved
Approval date: 08/02/2022
Contact: