Trial record 1 of 1 for:
CLOU064C12302
Efficacy and Safety of Remibrutinib Compared to Teriflunomide in Participants With Relapsing Multiple Sclerosis (RMS) (REMODEL-2)
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| ClinicalTrials.gov Identifier: NCT05156281 |
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Recruitment Status :
Recruiting
First Posted : December 14, 2021
Last Update Posted : April 24, 2024
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Sponsor:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
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Brief Summary:
To compare the efficacy and safety of remibrutinib versus teriflunomide in patients with relapsing multiple sclerosis (RMS)
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Relapsing Multiple Sclerosis | Drug: Remibrutinib Drug: Teriflunomide | Phase 3 |
The study CLOU064C12302 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 (CLOU064C12301) will be conducted simultaneously. Both studies will be conducted globally and data from the two studies will be pooled for some of the endpoints.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 800 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | Eligible participants will be randomized in a 1:1 ratio |
| Masking: | Double (Participant, Investigator) |
| Masking Description: | In order to maintain blinding, a double-dummy design will be used |
| Primary Purpose: | Treatment |
| Official 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 |
| Actual Study Start Date : | December 13, 2021 |
| Estimated Primary Completion Date : | April 30, 2026 |
| Estimated Study Completion Date : | October 30, 2030 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Multiple sclerosis
MedlinePlus related topics:
Multiple Sclerosis
Drug Information
available for:
Teriflunomide
| Arm | Intervention/treatment |
|---|---|
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Experimental: Remibrutinib - Core
Remibrutinib tablet and matching placebo of teriflunomide capsule
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Drug: Remibrutinib
tablet taken orally
Other Name: LOU064 |
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Active Comparator: Teriflunomide - Core
Teriflunomide capsule and matching placebo remibrutinib tablet
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Drug: Teriflunomide
capsule taken orally |
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Experimental: Remibrutinib - Extension
Participants on remibrutinib in Core will continue on remibrutinib tablet
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Drug: Remibrutinib
tablet taken orally
Other Name: LOU064 |
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Experimental: Remibrutinib - Extension (on teriflunomide in Core)
Participants on teriflunomide in Core will switch to remibrutinib tablet
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Drug: Remibrutinib
tablet taken orally
Other Name: LOU064 |
Primary Outcome Measures :
- Annualized relapse rate (ARR) of confirmed relapses [Core Part] [ Time Frame: From Baseline, up to 30 months ]ARR is the average number of confirmed MS relapses in a year
Secondary Outcome Measures :
- Time to 3-month confirmed disability progression (3mCDP) on Expanded Disability Status Scale (EDSS) [Core Part] (pooled data) [ Time Frame: Baseline up to 30 months ]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 [Core Part] (pooled data) [ Time Frame: Baseline up to 30 months ]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 [Core Part] [ Time Frame: Baseline up to 30 months ]Number of new/newly enlarged T2 lesions per year
- Neurofilament light chain (Nfl) [Core Part] [ Time Frame: Baseline up to 30 months ]Neurofilament light chain (NfL) concentration in serum
- Number of Gd-enhancing T1 lesions per MRI scan [Core Part] [ Time Frame: Baseline up to 30 months ]Average number of Gd-enhancing T1 lesions per scan
- Percentage of participants with No Evidence of Disease Activity-3 (NEDA-3) [Core Part] (pooled data) [ Time Frame: Baseline up to 30 months ]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 [Core Part] [ Time Frame: Baseline up to 30 months ]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 [Core Part] (pooled data) [ Time Frame: Baseline up to 30 months ]Decrease in Expanded Disability Status Scale Score (EDSS) which is sustained for at least 6 months
- Time to 3-months confirmed disability progression (3mCDP) and 6-month confirmed disability progression (6mCDP) independent of relapse activity (PIRA) [Core Part] (pooled data) [ Time Frame: Baseline up to 30 months ]Time to 3-month confirmed disability progression (3mCDP) and 6-month confirmed disability progression (6mCDP) is defined as an increase in Expanded Disability Status Scale (EDSS) which is sustained for at least 3 months or 6 months, respectively, without an on-study relapse before or on the day of a progression eve
- Change from baseline in the Symbol Digit Modalities Test (SDMT) [Core Part] (pooled data) [ Time Frame: Baseline up to 30 months ]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) [Core Part] (pooled data) [ Time Frame: Baseline, up to 30 months ]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) (pooled data) [Core Part] (pooled data) [ Time Frame: Baseline up to 30 months ]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) [Core Part] (pooled data) [ Time Frame: Baseline up to 30 months ]The composite involves CDP and worsening by at least 20% in T25FW and 9HPT
- Change from Baseline in T2 lesion volume [Core Part] [ Time Frame: Baseline up to 30 months ]Change from baseline in total T2 lesion volume.
- Change from baseline in Multiple Sclerosis Impact Scale (MSIS-29) [Core Part] [ Time Frame: Baseline up to 30 months ]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) [Core Part] [ Time Frame: Baseline up to 30 months ]Adverse events and SAEs including clinically significant, laboratory data, vital signs, electrocardiogram (ECG), Columbia Suicide Severity Rating
- Pharmacokinetics of remibrutinib [Core Part] [ Time Frame: Month 1, Month 6 ]Blood concentrations of remibrutinib
- Number of participants with Adverse events and Serious adverse events (SAE) [Extension Part] [ Time Frame: 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] [ Time Frame: 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] [ Time Frame: 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] [ Time Frame: 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] [ Time Frame: 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] [ Time Frame: Day 1 Extension up to 5 years ]Neurofilament light chain (NfL) concentration in serum
- Change from baseline in Multiple Sclerosis Impact Scale (MSIS-29) [Extension Part] [ Time Frame: 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
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years to 55 Years (Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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 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
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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 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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05156281
Contacts
| Contact: Novartis Pharmaceuticals | 1-888-669-6682 | novartis.email@novartis.com | |
| Contact: Novartis Pharmaceuticals | +41613241111 |
Locations
Show 226 study locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
| Study Director: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
| Responsible Party: | Novartis Pharmaceuticals |
| ClinicalTrials.gov Identifier: | NCT05156281 |
| Other Study ID Numbers: |
CLOU064C12302 2020-005929-89 ( EudraCT Number ) |
| First Posted: | December 14, 2021 Key Record Dates |
| Last Update Posted: | April 24, 2024 |
| Last Verified: | April 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan 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 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
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MS RMS RRMS active secondary progressive multiple sclerosis SPMS remibrutinib LOU064 teriflunomide adult |
relapse Expanded Disability Status Scale T2 lesions T1 lesions GD- enhancing MRI Neurofilament light chain McDonald diagnostic criteria |
Additional relevant MeSH terms:
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Multiple Sclerosis Sclerosis Pathologic Processes Demyelinating Autoimmune Diseases, CNS Autoimmune Diseases of the Nervous System Nervous System Diseases Demyelinating Diseases Autoimmune Diseases Immune System Diseases Teriflunomide Remibrutinib Anti-Inflammatory Agents, Non-Steroidal |
Analgesics, Non-Narcotic Analgesics Sensory System Agents Peripheral Nervous System Agents Physiological Effects of Drugs Anti-Inflammatory Agents Antirheumatic Agents Immunosuppressive Agents Immunologic Factors Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |