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

See if you Pre-qualify

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

Novartis Investigative Site

Recruiting

Capital Federal,Buenos Aires,1424,Argentina

Novartis Investigative Site

Recruiting

Rosario,Santa Fe,2000,Argentina

Novartis Investigative Site

Recruiting

Buenos Aires,C1012aar,Argentina

Novartis Investigative Site

Recruiting

Caba,C1424byd,Argentina

Novartis Investigative Site

Recruiting

Capital Federal,C1023aab,Argentina

Novartis Investigative Site

Recruiting

Santiago del Estero,4200,Argentina

Novartis Investigative Site

Recruiting

Caba,Buenos Aires,C1122aak,Argentina

Novartis Investigative Site

Recruiting

Graz,A-8036,Austria

Novartis Investigative Site

Recruiting

Klagenfurt,9020,Austria

Novartis Investigative Site

Recruiting

Linz,4020,Austria

Novartis Investigative Site

Recruiting

Linz,Oberoesterreich,A 4020,Austria

Novartis Investigative Site

Recruiting

Brugge,8000,Belgium

Novartis Investigative Site

Recruiting

Bruxelles,1070,Belgium

Novartis Investigative Site

Recruiting

Melsbroek,1820,Belgium

Novartis Investigative Site

Recruiting

Pelt,3900,Belgium

Novartis Investigative Site

Recruiting

Edegem,Antwerpen,2650,Belgium

Novartis Investigative Site

Recruiting

Antwerpen,2018,Belgium

Novartis Investigative Site

Recruiting

Brasschaat,2930,Belgium

Novartis Investigative Site

Recruiting

Sofia,1680,Bulgaria

Novartis Investigative Site

Recruiting

Pleven,5800,Bulgaria

Novartis Investigative Site

Recruiting

Sofia,1113,Bulgaria

Novartis Investigative Site

Recruiting

Sofia,1431,Bulgaria

Novartis Investigative Site

Recruiting

Santiago,Region Metropolitana,7650568,Chile

Novartis Investigative Site

Recruiting

Santiago,Region Metropolitana,8431657,Chile

Novartis Investigative Site

Recruiting

Beijing,100730,China

Novartis Investigative Site

Recruiting

Zhengzhou,Henan,450052,China

Novartis Investigative Site

Recruiting

Chongqing,400016,China

Novartis Investigative Site

Recruiting

Changsha,Hunan,410008,China

Novartis Investigative Site

Recruiting

Tianjin,300052,China

Novartis Investigative Site

Recruiting

Baotou,Inner Mongolia,014040,China

Novartis Investigative Site

Recruiting

Hohhot,Inner Mongolia,010017,China

Novartis Investigative Site

Recruiting

Beijing,Beijing,100000,China

Novartis Investigative Site

Recruiting

Nanchang,Jiangxi,330006,China

Novartis Investigative Site

Recruiting

Guangzhou City,Guangdong,510000,China

Novartis Investigative Site

Recruiting

Changchun,Jilin,130021,China

Novartis Investigative Site

Recruiting

Guangzhou,Guangdong,510080,China

Novartis Investigative Site

Recruiting

Medellin,050001,Colombia

Novartis Investigative Site

Recruiting

Puerto Colombia,Atlantico,080012,Colombia

Novartis Investigative Site

Recruiting

Cali,Valle Del Cauca,760001,Colombia

Novartis Investigative Site

Recruiting

Cali,Valle Del Cauca,760012,Colombia

Novartis Investigative Site

Recruiting

Bogota,110110,Colombia

Novartis Investigative Site

Recruiting

Rijeka,HRV,51000,Croatia

Novartis Investigative Site

Recruiting

Osijek,31000,Croatia

Novartis Investigative Site

Recruiting

Zadar,23000,Croatia

Novartis Investigative Site

Recruiting

Zagreb,10000,Croatia

Novartis Investigative Site

Recruiting

Slagelse,Dk-4200,Denmark

Novartis Investigative Site

Recruiting

Tbilisi,114,Georgia

Novartis Investigative Site

Recruiting

Tbilisi,141,Georgia

Novartis Investigative Site

Recruiting

Tbilisi,159,Georgia

Novartis Investigative Site

Recruiting

Tbilisi,160,Georgia

Novartis Investigative Site

Recruiting

Tbilisi,172,Georgia

Novartis Investigative Site

Recruiting

Tbilisi,179,Georgia

Novartis Investigative Site

Recruiting

Guatemala,01015,Guatemala

Novartis Investigative Site

Recruiting

Sha Tin,Hong Kong

Novartis Investigative Site

Recruiting

Ludhiana,Punjab,141008,India

Novartis Investigative Site

Recruiting

Lucknow,Uttar Pradesh,226014,India

Novartis Investigative Site

Recruiting

Dehradun,Uttarakhand,248001,India

Novartis Investigative Site

Recruiting

New Delhi,Delhi,110017,India

Novartis Investigative Site

Recruiting

Mangalore,575018,India

Novartis Investigative Site

Recruiting

Mumbai,Maharashtra,400008,India

Novartis Investigative Site

Recruiting

Nashik,Maharashtra,422005,India

Novartis Investigative Site

Recruiting

Chandigarh,Punjab,160012,India

Novartis Investigative Site

Recruiting

Dublin 4,Do4,Ireland

Novartis Investigative Site

Recruiting

Dublin,Dublin 8,Ireland

Novartis Investigative Site

Recruiting

Ashkelon,78278,Israel

Novartis Investigative Site

Recruiting

Hadera,38100,Israel

Novartis Investigative Site

Recruiting

Haifa,310 9601,Israel

Novartis Investigative Site

Recruiting

Sefad,13100,Israel

Novartis Investigative Site

Recruiting

Tel Aviv,6423906,Israel

Novartis Investigative Site

Recruiting

Roma,RM,00133,Italy

Novartis Investigative Site

Recruiting

Roma,RM,00168,Italy

Novartis Investigative Site

Recruiting

Roma,RM,00189,Italy

Novartis Investigative Site

Recruiting

Verona,VR,37134,Italy

Novartis Investigative Site

Recruiting

Napoli,80131,Italy

Novartis Investigative Site

Recruiting

Montichiari,BS,25018,Italy

Novartis Investigative Site

Recruiting

Novara,28100,Italy

Novartis Investigative Site

Recruiting

Milano,MI,20132,Italy

Novartis Investigative Site

Recruiting

Amman,1857,Jordan

Novartis Investigative Site

Recruiting

Riga,LV,Lv-1005,Latvia

Novartis Investigative Site

Recruiting

Riga,Lv 1002,Latvia

Novartis Investigative Site

Recruiting

Tripoli,Crpj+66c,Lebanon

Novartis Investigative Site

Recruiting

El Chouf,LBN,1503201002,Lebanon

Novartis Investigative Site

Recruiting

Ashrafieh,166830,Lebanon

Novartis Investigative Site

Recruiting

Beirut,166378,Lebanon

Novartis Investigative Site

Recruiting

Beirut,6301,Lebanon

Novartis Investigative Site

Recruiting

Siauliai,LTU,76231,Lithuania

Novartis Investigative Site

Recruiting

Klaipeda,Lt-92288,Lithuania

Novartis Investigative Site

Recruiting

Seberang Jaya,Pulau Pinang,13700,Malaysia

Novartis Investigative Site

Recruiting

Kuala Terengganu,Terengganu,20400,Malaysia

Novartis Investigative Site

Recruiting

Kuala Lumpur,50589,Malaysia

Novartis Investigative Site

Recruiting

San Pedro Garza Garcia,66278,Mexico

Novartis Investigative Site

Recruiting

Veracruz,91900,Mexico

Novartis Investigative Site

Recruiting

Rotterdam,3079 dz,Netherlands

Novartis Investigative Site

Recruiting

Lodz,90 324,Poland

Novartis Investigative Site

Recruiting

Lodz,93-113,Poland

Novartis Investigative Site

Recruiting

Lublin,20-410,Poland

Novartis Investigative Site

Recruiting

Piotrkow Trybunalski,97300,Poland

Novartis Investigative Site

Recruiting

Wroclaw,Dolnoslaskie,52 416,Poland

Novartis Investigative Site

Recruiting

Poznan,60-693,Poland

Novartis Investigative Site

Recruiting

Bydgoszcz,Woj Kujawsko-pomorskie,85-796,Poland

Novartis Investigative Site

Recruiting

Rzeszow,35-323,Poland

Novartis Investigative Site

Recruiting

Kielce,25 726,Poland

Novartis Investigative Site

Recruiting

Szczecin,70111,Poland

Novartis Investigative Site

Recruiting

Khorais Street,Riyadh,11426,Saudi Arabia

Novartis Investigative Site

Recruiting

Jeddah,21423,Saudi Arabia

Novartis Investigative Site

Recruiting

Jeddah,21499,Saudi Arabia

Novartis Investigative Site

Recruiting

Nitra,94901,Slovakia

Novartis Investigative Site

Recruiting

Trnava,91702,Slovakia

Novartis Investigative Site

Recruiting

Kosice,Slovak Republic,04066,Slovakia

Novartis Investigative Site

Recruiting

Bratislava,82606,Slovakia

Novartis Investigative Site

Recruiting

Madrid,28006,Spain

Novartis Investigative Site

Recruiting

El Palmar,Murcia,30120,Spain

Novartis Investigative Site

Recruiting

Valladolid,Castilla Y Leon,47011,Spain

Novartis Investigative Site

Recruiting

Madrid,28034,Spain

Novartis Investigative Site

Recruiting

Vigo,Pontevedra,36212,Spain

Novartis Investigative Site

Recruiting

Salt,Cataluna,17190,Spain

Novartis Investigative Site

Recruiting

Madrid,28040,Spain

Novartis Investigative Site

Recruiting

Cadiz,Andalucia,11009,Spain

Novartis Investigative Site

Recruiting

Castilleja De La Cuesta,Sevilla,41950,Spain

Novartis Investigative Site

Recruiting

Valencia,Comunidad Valenciana,46010,Spain

Novartis Investigative Site

Recruiting

Madrid,28222,Spain

Novartis Investigative Site

Recruiting

Cordoba,Andalucia,14004,Spain

Novartis Investigative Site

Recruiting

Barcelona,08035,Spain

Novartis Investigative Site

Recruiting

La Coruna,Galicia,15006,Spain

Novartis Investigative Site

Recruiting

Malaga,Andalucia,29010,Spain

Novartis Investigative Site

Recruiting

Las Palmas de Gran Canaria,35010,Spain

Novartis Investigative Site

Recruiting

Alcorcon,Madrid,28922,Spain

Novartis Investigative Site

Recruiting

Sevilla,Andalucia,41014,Spain

Novartis Investigative Site

Recruiting

Leon,24080,Spain

Novartis Investigative Site

Recruiting

Getafe,Madrid,28905,Spain

Novartis Investigative Site

Recruiting

Sant Joan Despi,Barcelona,08970,Spain

Novartis Investigative Site

Recruiting

Basel,4031,Switzerland

Novartis Investigative Site

Recruiting

Bern,3010,Switzerland

Novartis Investigative Site

Recruiting

Tainan,70403,Taiwan

Novartis Investigative Site

Recruiting

Taipei,11220,Taiwan

Novartis Investigative Site

Recruiting

Taoyuan,33305,Taiwan

Novartis Investigative Site

Recruiting

Kaohsiung,83301,Taiwan

Novartis Investigative Site

Recruiting

Dubai,United Arab Emirates

Novartis Investigative Site

Recruiting

Winchester,Hampshire,So21 1hu,United Kingdom

Novartis Investigative Site

Recruiting

Glasgow,G51 4tf,United Kingdom

Novartis Investigative Site

Recruiting

Westbruy On Trym,Bristol,Bs10 5nb,United Kingdom

The Neurological Institute PA

Recruiting

Charlotte,North Carolina,28204,United States