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Trial details
Efficacy and Safety of Remibrutinib Compared to Teriflunomide in Participants With Relapsing Multiple Sclerosis
Current status:
Approved
|
Date registered:
27/02/2023
Trial version(s)
History: 14/10/2022
History: 14/10/2022
History: 14/10/2022
History: 14/10/2022
Current: 14/10/2022
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Main Information
Primary registry identifying number
LBCTR2023015151
Protocol number
CLOU064C12301
MOH registration number
Trial already registered with the MoPH
Study registered at the country of origin
Type of registration
Prospective
Date of registration in national regulatory agency
Primary sponsor
Novartis Pharma AG
Primary sponsor: Country of origin
Novartis Pharma AG
Public title
Efficacy and Safety of Remibrutinib Compared to Teriflunomide in Participants With Relapsing Multiple Sclerosis
Acronym
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
Acronym
Brief summary of the study: English
To compare the efficacy and safety of remibrutinib versus teriflunomide in patients with relapsing multiple sclerosis
Brief summary of the study: Arabic
مقارنة فعالية وسلامة دواء ريميبروتينيب مقابل دواء تيريفلونوميد لدى مشاركين مصابين بالتصلّب المتعدد الانتكاسي
Health conditions/problem studied: Specify
Relapsing Multiple Sclerosis
Interventions: Specify
Drug: Remibrutinib tablet taken orally Other Name: LOU064 Drug: Teriflunomide capsule taken orally
Key inclusion and exclusion 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 Inclusion to Extension part: - Patients 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
Key inclusion and exclusion criteria: Gender
Both
Key inclusion and exclusion criteria: Age minimum
18
Key inclusion and exclusion criteria: Age maximum
55
Key inclusion and exclusion criteria: 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 or hepatic failure or participants with moderate or severe hepatic impairment (Child-Pugh class C) 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 (prior to randomization) - 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 strong CYP3A4 inducers within two weeks prior to randomization Other inclusion and exclusion criteria may apply
Type of Study
Type
Interventional
Type of intervention
Pharmaceutical
Trial scope
Therapy
Trial scope: Specify scope
Study design: Allocation
Randomized controlled trial
Study design: Masking
Blinded (masking used)
Study design: Control
Active
Study phase
3
Study design: Purpose
Treatment
Study design: Assignment
Parallel
IMP has market authorization
No
Name of IMP
Remibrutinib
Type of IMP
Immunological
Pharmaceutical class
Bruton's Tyrosine Kinase (BTK) Inhibitor
Therapeutic indication
Relapsing Multiple Sclerosis
Therapeutic benefit
Treatment
Biospecimen retention
Samples with DNA**
Biospecimen description
Samples will be shipped to Q2 solutions central lab
Target sample size
16
Actual enrollment target size
Date of first enrollment: Type
Anticipated
Date of first enrollment: Date
01/04/2023
Date of study closure: Type
Anticipated
Date of study closure: Date
23/11/2029
Recruitment status
Pending
Date of completion
IPD sharing statement plan
Yes
IPD sharing statement description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Additional data URL
https://clinicaltrials.gov/ct2/show/record/NCT05147220?term=CLOU064C12301&draw=2&rank=1
Summary Results
Secondary Identifying Numbers
Full name of issuing authority
Secondary identifying number
Clinicaltrials.gov
NCT05147220
Sources of Monetary or Material Support
Name
Novartis Pharma AG
Secondary Sponsors
Name
NA
Contact for Public/Scientific Queries
Contact type
First name
Last name
Address
Country
Telephone
Email
Affiliation
Public
Halim
Abboud
Beirut
Lebanon
009613535711
halimabboud@hotmail.com
Hotel Dieu De France
Scientific
Hind
Khairallah
Sin El Fil
Lebanon
009611512002 Ext. 271
hind.khairallah@fattal.com.lb
Khalil Fattal et Fils s.a.l
Public
Shawkat
Beayni
Al Chouf
Lebanon
009613700357
shwakat.beayni@gmail.com
Ain Wazein Medical Village
Public
Aline
Mourad
Beirut
Lebanon
0096170472332
aemourad@stgeorgehospital.org
Saint George Hospital University Medical Center
Public
Hania
Jarkass
Beirut
Lebanon
009613043242
haniahabi@hotmail.com
Makassed General Hospital
Centers/Hospitals Involved in the Study
Center/Hospital name
Name of principles investigator
Principles investigator speciality
Ethical approval
Hotel Dieu De France
Halim Abboud
Neurology
Approved
Ain Wazein Medical Village
Shawkat Beayni
Neurology
Approved
Saint George Hospital University Medical Center
Aline Mourad
Neurology
Approved
Makassed General Hospital
Hania Jarkass
Neurology
Approved
Ethics Review
Ethics approval obtained
Approval date
Contact name
Contact email
Contact phone
Hotel Dieu de France
03/10/2022
Sami Richa
cue@usj.edu.lb
+9611421229
Ain w Zein Medical Village
11/11/2022
Khaled Abdel Baki
Khaled.abdelbaki@awmedicalvillage.org
+9615509001 ext 2115
Saint George Hospital University Medical Center
15/12/2022
Michel Daher
mndaher@stgeorgehospital.org
+9611441733
Makassed General Hospital
30/11/2022
Mariam Rajab
Research.makassed@hotmail.com
+9611636941
Countries of Recruitment
Name
Argentina
Belgium
Bulgaria
China
Croatia
Guatemala
India
Italy
Latvia
Malaysia
Netherlands
Poland
Russian Federation
Slovakia
Spain
Switzerland
United Kingdom
United States of America
Health Conditions or Problems Studied
Condition
Code
Keyword
Relapsing Multiple Sclerosis
Multiple sclerosis (G35)
Relapsing Multiple Sclerosis
Interventions
Intervention
Description
Keyword
Consenting, IMP administration, Laboratory testing, Imaging
Consenting, IMP administration, Laboratory testing, Imaging
Consenting, IMP administration, Laboratory testing, Imaging
Primary Outcomes
Name
Time points
Measure
Annualized relapse rate (ARR) of confirmed relapses
Baseline up to 30 month
ARR is the average number of confirmed MS relapses in a year
Key Secondary Outcomes
Name
Time points
Measure
Time to 3-month confirmed disability progression (3mCDP) on Expanded Disability Status Scale (EDSS)
Baseline up to 30 month
Time to 3-month confirmed disability progression (3mCDP) is defined as an increase in Expanded Disability Status Scale (EDSS) which is sustained for at least 3 months
Time to 6-month confirmed disability progression (6mCDP) on EDSS
Baseline up to 30 month
Time to 6-month confirmed disability progression (6mCDP) is defined as an increase in Expanded Disability Status Scale (EDSS) which is sustained for at least 6 months
Annualized rate of new or enlarging T2 lesion
Baseline up to 30 month
Number of new/newly enlarged T2 lesions per year
Neurofilament light chain (Nfl)
Baseline up to 30 months
Neurofilament light chain (NfL) concentration in serum
Number of Gd-enhancing T1 lesions per MRI scan
Baseline up to 30 month
Average number of Gd-enhancing T1 lesions per scan
Percentage of participants with No Evidence of Disease Activity-3 (NEDA-3)
Baseline up to 30 month
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
Time to first confirmed relapse
Baseline up to 30 month
Change in the Expanded Disability Status Scale (EDSS), an increase of at least 0.5 points on the EDSS (total) score, or an increase of at least 1 point on at least two functional scores (FSs), or an increase of at least 2 points on at least one FS, excluding changes involving bowel/bladder or cerebral FS, compared to the previous available rating
Time to 6-month confirmed disability improvement (6mCDI) on EDSS
Baseline up to 30 month
Decrease in Expanded Disability Status Scale Score (EDSS) which is sustained for at least 6 months
Change from baseline in the Symbol Digit Modalities Test (SDMT)
Baseline up to 30 month
Symbol Digit Modalities Test (SDMT), an array of symbols paired with empty spaces, measures processing in speed; participants verbally match the number for each symbol as rapidly as possible. The score is the number of correctly coded items in 90 seconds. Higher scores indicate improvement. Lower scores indicate worsening
Time to 6-month confirmed worsening by at least 20% in the Timed 25-foot walk test (T25FW)
Baseline, up to 30 month
The patient walking speed to cover 25 foot distance is recorded in seconds. Longer time indicates poorer lower limb function. 20% worsening is defined as 20% increase from baseline T25FW score
Time to 6-month confirmed worsening by at least 20% in the Timed 9-hole peg test (9HPT)
Baseline up to 30 month
The patient's right and left arm function to peg 9 holes measured in seconds. Longer time indicates poorer upper limb function. 20% worsening is defined as 20% increase from baseline 9HPT score in at least one hand (average of two trials per hand)
Time to composite 6-month confirmed disability Progression (CDP)
Baseline up to 30 month
The composite involves CDP and worsening by at least 20% in T25FW and 9HPT
Change from Baseline in T2 lesion volume
Baseline up to 30 month
Change from baseline in total T2 lesion volume
Change from baseline in Fatigue Symptoms and Impacts Questionnaire - Relapsing Multiple Sclerosis (FSIQ-RMS)
Baseline up to 30 month
20-item, self-administered questionnaire. Global score ranges from 0 to 100 where higher score represents greater fatigue
Change from baseline in Generalized Anxiety Disorder Scale (GAD-7)
Baseline up to 30 month
7-item, self-administered scale. It has a global score ranging from 0-21. Higher score means higher severity of anxiety symptoms
Change from baseline in Patient Health Questionnaire-9 (PHQ-9)
Baseline up to 30 month
9-item, self-administered scale. Scores can range from 0 to 27. PHQ-9 scores of 5, 10, 15, and 20 represent mild, moderate, moderately severe, and severe depression, respectively
Change from baseline in Brief Pain Inventory- short form (BPI-SF)
Baseline up to 30 month
15-item, self-administered questionnaire to assess the severity of pain and the impact of pain on daily functions. Includes seven-item interference scale. It has a 10-point response option, ranging from 0 (does not interfere) to 10 (completely interferes). Global score ranges from 0 to 10, where lower scores represent lower pain
Change from baseline in Health Utilities Index (HUI-Ill)
Baseline up to 30 month
15-item, self-administered index that measures eight health-related quality of life areas including vision, hearing, speech, ambulation/mobility, pain, dexterity, emotion, and cognition
Change from baseline in Multiple Sclerosis Impact Scale (MSIS-29)
Baseline up to 30 month
29-item, self-administered questionnaire that includes 2 domains, physical and psychological. Responses are captured on a 4-point scale ranging from "not at all" (1) to "extremely" (4), where higher scores reflect greater impact on day to day life
Number of participants with Adverse events and Serious adverse events(SAE)
Baseline up to 30 month
Adverse events and SAEs including clinically significant , laboratory data, vital signs, electrocardiogram (ECG), Columbia Suicide Severity Rating
Pharmacokinetics of remibrutinib
Month 1, Month 6
Blood concentrations of remibrutinib
Number of participants with Adverse events and Serious adverse events (SAE)
Day 1 Extension up to 5 years
Adverse events and SAEs including clinically significant, laboratory data, vital signs, electrocardiogram (ECG), Columbia Suicide Severity Rating
Annualized relapse rate (ARR) of confirmed relapses [Extension Part]
Day 1 Extension up to 5 years
ARR is the average number of confirmed MS relapses in a year
Annualized rate of new or enlarging T2 lesion [Extension Part]
Day 1 Extension up to 5 years
Number of new/newly enlarged T2 lesions per year
Time to 6-month confirmed disability progression (6mCDP) on EDSS [Extension Part]
Day 1 Extension up to 5 years
Time to 6-month confirmed disability progression (6mCDP) is defined as an increase in Expanded Disability Status Scale (EDSS) which is sustained for at least 6 months
Change from baseline in the Symbol Digit Modalities Test (SDMT) [Extension Part]
Day 1 Extension up to 5 years
Symbol Digit Modalities Test (SDMT), an array of symbols paired with empty spaces, measures processing in speed; participants verbally match the number for each symbol as rapidly as possible. The score is the number of correctly coded items in 90 seconds. Higher scores indicate improvement. Lower scores indicate worsening
Neurofilament light chain (NfL) [Extension Part]
Day 1 Extension up to 5 years
Neurofilament light chain (NfL) concentration in serum
Change from baseline in Fatigue Symptoms and Impacts Questionnaire - Relapsing Multiple Sclerosis (FSIQ-RMS) [Extension Part]
Day 1 Extension up to 5 years
20-item, self-administered questionnaire. Global score ranges from 0 to 100 where higher score represents greater fatigue
Change from baseline in Generalized Anxiety Disorder Scale (GAD-7) [Extension Part]
Day 1 Extension up to 5 years
7-item, self-administered scale. It has a global score ranging from 0-21. Higher score means higher severity of anxiety symptoms
Change from baseline in Patient Health Questionnaire-9 (PHQ-9) [Extension Part]
Day 1 Extension up to 5 years
9-item, self-administered scale. Scores can range from 0 to 27. PHQ-9 scores of 5, 10, 15, and 20 represent mild, moderate, moderately severe, and severe depression, respectively
Change from baseline in Brief Pain Inventory- short form (BPI-SF) [Extension Part]
Day 1 Extension up to 5 years
15-item, self-administered questionnaire to assess the severity of pain and the impact of pain on daily functions. Includes seven-item interference scale. It has a 10-point response option, ranging from 0 (does not interfere) to 10 (completely interferes). Global score ranges from 0 to 10, where lower scores represent lower pain
Change from baseline in Health Utilities Index (HUI-Ill) [Extension Part]
Day 1 Extension up to 5 years
15-item, self-administered index that measures eight health-related quality of life areas including vision, hearing, speech, ambulation/mobility, pain, dexterity, emotion, and cognition
Change from baseline in Multiple Sclerosis Impact Scale (MSIS-29) [Extension Part]
Day 1 Extension up to 5 years
29-item, self-administered questionnaire that includes 2 domains, physical and psychological. Responses are captured on a 4-point scale ranging from "not at all" (1) to "extremely" (4), where higher scores reflect greater impact on day to day life
Trial Results
Summary results in Lebanon
Study results globally
Date of posting of results summaries
Date of first journal publication of results
Results URL link
Baseline characteristics
Participant flow
Adverse events
Outcome measures
URL to protocol files
Link(s) to publications related to the study
Changes History
Change
Date
Adding new site SGHUMC
20/02/2023
Adding new site MGH
20/02/2023
Download as PDF
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