Efficacy and Safety of Remibrutinib Compared to Teriflunomide in Participants With Relapsing Multiple Sclerosis (RMS)

Last Update: Sep 19, 2024

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

ClinicalTrials.gov Identifier:

NCT05147220

Novartis Reference Number:CLOU064C12301

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation.

Study Description

To compare the efficacy and safety of remibrutinib versus teriflunomide in patients with
relapsing multiple sclerosis (RMS) The study CLOU064C12301 consists of an initial Core Part (CP) (maximum duration per
participant of up to 30 months), followed by an Extension Part (EP, of up to 5 years
duration) for eligible participants.

The Core Part is a randomized, double-blind, double-dummy, active comparator-controlled,
fixed-dose, parallel-group, multi-center study in approximately 800 participants with
relapsing multiple sclerosis (RMS).

The Extension Part is an open-label, single-arm, fixed-dose design in which eligible
participants are treated with remibrutinib for up to 5 years.

A second study of identical design (CLOU064C12302) will be conducted simultaneously. Both
studies will be conducted globally and data from the two studies will be pooled for some
of the endpoints.

Condition

Relapsing Multiple Sclerosis

Phase

Phase3

Overall Status

Recruiting

Number of Participants

800

Start Date

Dec 16, 2021

Completion Date

Oct 30, 2030

Gender

All

Age(s)

18 Years - 55 Years (Adult)

Interventions

Drug

Remibrutinib

tablet taken orally

Drug

Teriflunomide

capsule taken orally

Eligibility Criteria

Inclusion Criteria:

- 18 to 55 years of age

- Diagnosis of RMS according to the 2017 McDonald diagnostic criteria

- At least: 1 documented relapse within the previous year. OR 2 documented relapses
within the previous 2 years, OR 1 active Gadolinium (Gd)-enhancing lesion in the 12
months.

- EDSS score of 0 to 5.5 (inclusive)

- Neurologically stable within 1 month

Exclusion Criteria:

- Diagnosis of primary progressive multiple sclerosis (PPMS)

- Disease duration of more than 10 years in participants with EDSS score of 2 or less
at screening

- History of clinically significant CNS disease other than MS

- Ongoing substance abuse (drug or alcohol)

- History of malignancy of any organ system (other than complete resection of
localized basal cell carcinoma of the skin or in situ cervical cancer),

- Participants with history of confirmed Progressive Multifocal Leukoencephalopathy
(PML) or Neurological symptoms consistent with PML

- suicidal ideation or behavior

- Evidence of clinically significant cardiovascular, neurological, psychiatric,
pulmonary , renal, hepatic, endocrine, metabolic, hematological disorders or
gastrointestinal disease that can interfere with interpretation of the study results
or protocol adherence

- Participants who have had a splenectomy

- Active clinically significant systemic bacterial, viral, parasitic or fungal
infections

- Positive results for syphilis or tuberculosis testing

- Uncontrolled disease states, such as asthma, or inflammatory bowel disease, where
flares are commonly treated with oral or parenteral corticosteroids

- Active, chronic disease of the immune system (including stable disease treated with
immune therapy (e.g. Leflunomide, Methotrexate)) other than MS (e.g. rheumatoid
arthritis, systemic lupus erythematosus, etc.) with the exception of well-controlled
diabetes or thyroid disorder.

- Participants with a known immunodeficiency syndrome (AIDS, hereditary immune
deficiency, drug induced immune deficiency), or tested positive for HIV antibody

- History or current treatment for hepatic disease including but not limited to acute
or chronic hepatitis, cirrhosis (including all Child-Pugh classes) or hepatic
failure or any chronic liver or biliary disease.

- History of severe renal disease or creatinine level

- Participants at risk of developing or having reactivation of hepatitis

- Hematology parameters at screening:

- Hemoglobin: < 10 g/dl (<100g/L)

- Platelets: < 100000/mm3 (<100 x 109/L)

- Absolute lymphocyte count < 800/mm3 (<0.8 x 109/L)

- White blood cells: <3 000/mm3 (<3.0 x 109/L)

- Neutrophils: < 1 500/mm3 (<1.5 x 109/L)

- B-cell count < 50% lower limit of normal (LLN) or total IgG & total IgM < LLN
(only required for participants who had a history of receiving B-cell
therapies, such as rituximab, ocrelizumab or ofatumumab, prior to screening)

- History or current diagnosis of significant ECG abnormalities

- Resting QTcF ≥450 msec (male) or ≥460 msec (female) at pre-treatment as per central
ECG reading at screening visit

- Use of other investigational drugs

- Requirement for anticoagulant medication or use of dual anti-platelet therapy
Significant bleeding risk or coagulation disorders,

- History of gastrointestinal bleeding

- Major surgery within 8 weeks prior to screening

- History of hypersensitivity to any of the study drugs or excipients

- Pregnant or nursing (lactating) female participants, prior to randomization

- Women of childbearing potential not using highly effective contraception

- Sexually active males not agreeing to use condom

- Have received any live or live-attenuated vaccines within 6 weeks of randomization
or requirement to receive these vaccinations during study

- Use of strong CYP3A4 inhibitors or use of moderate or strong CYP3A4 inducers within
two weeks prior to randomization

Inclusion to Extension part:

• Participants who complete the Core Part of the study on double-blind study treatment
and conduct the Accelerated Elimination Procedure (AEP)

Other inclusion and exclusion criteria may apply

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