Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Relapsing Forms of Multiple Sclerosis (RMS) Study of Bruton's Tyrosine Kinase (BTK) Inhibitor Tolebrutinib (SAR442168) (GEMINI 1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04410978
Recruitment Status : Recruiting
First Posted : June 1, 2020
Last Update Posted : July 13, 2021
Sponsor:
Information provided by (Responsible Party):
Sanofi

Tracking Information
First Submitted Date  ICMJE May 28, 2020
First Posted Date  ICMJE June 1, 2020
Last Update Posted Date July 13, 2021
Actual Study Start Date  ICMJE June 30, 2020
Estimated Primary Completion Date August 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 28, 2020)
Annualized Adjudicated Relapse Rate : Number of confirmed adjudicated protocol defined relapses [ Time Frame: Up to approximately 36 months ]
Annualized Adjudicated Relapse Rate : Number of confirmed adjudicated protocol defined relapses
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 25, 2021)
  • Time to onset of confirmed disability worsening confirmed over at least 6 months [ Time Frame: Up to approximately 36 months ]
    Time to onset of confirmed disability worsening (CDW), confirmed over at least 6 months, defined as follows:
    • increase of ≥1.5 points from the baseline expanded disability status scale (EDSS) score when the baseline score is 0 OR
    • increase of ≥1.0 point from the baseline EDSS score when the baseline score is 0.5 to ≤5.5 OR
    • increase of ≥0.5 point from the baseline EDSS score when the baseline score is >5.5 - 5.
  • Time to onset of CDW, assessed by the EDSS score and confirmed over at least 3 months [ Time Frame: Up to approximately 36 months ]
  • Total number of new and/or enlarging T2 hyperintense lesions as detected by MRI from Month 6 through the end of study (EOS) [ Time Frame: From 6 months up to approximately 36 months ]
  • Total of Gd-enhancing T1 hyperintense lesions as detected by MRI from 6 months through the EOS [ Time Frame: From 6 months up to approximately 36 months ]
  • Change in cognitive function [ Time Frame: From Baseline up to approximately 36 months ]
    Change in cognitive function from baseline to the end of study (EOS) as assessed by SDMT and by CVLT-II where available
  • Time to confirmed disability improvement [ Time Frame: From Baseline up to approximately 36 months ]
    Time to confirmed disability improvement (CDI), defined as a ≥1.0 point decrease on the EDSS from the baseline EDSS score confirmed over at least 6 months
  • Percent Change in Brain volume loss (BVL) [ Time Frame: From 6 months up to approximately 36 months ]
    Brain volume loss (BVL) rate as detected by brain MRI from Month 6 to the EOS
  • Change in Multiple Sclerosis Quality of Life [ Time Frame: From Baseline up to approximately 36 months ]
    Change in Multiple Sclerosis Quality of Life-54 (MSQoL-54) from the baseline through the EOS
  • Number of participants with adverse events A(Es) leading to permanent study intervention discontinuation, and adverse events of special interest (AESI) [ Time Frame: From screening until end of study approximately 36 months ]
  • Population Pharmacokinetics - Concentration SAR442168 and relevant metabolites at 6 months [ Time Frame: 6 Months ]
    Plasma concentration of SAR442168 (population PK assessment) at 6 Months
  • Population Pharmacokinetics Concentration of SAR442168 and relevant metabolites at 9 Months [ Time Frame: 9 Months ]
    Plasma concentration of SAR442168 (population PK assessment) at 9 Months
  • Population Pharmacokinetics - Concentration of SAR442168 and relevant metabolites at 12 Months [ Time Frame: 12 Months ]
    Plasma concentration of SAR442168 (population PK assessment) at 12 Months
  • Change in plasma NfL [ Time Frame: From Baseline until end of study approximately 36 months ]
    Change in plasma neurofilament light chain (NfL) levels at the EOS compared to baseline
  • Change in lymphocyte Phenotype [ Time Frame: From Baseline until end of study approximately 36 months ]
    Change in lymphocyte phenotype subsets in whole blood at the EOS compared to baseline in a subset of participants
  • Changes in plasma Immunoglobulin levels [ Time Frame: From Baseline until end of study (up to 36 months) ]
    Changes in serum immunoglobulin level at the EOS compared to baseline
  • Change in CHI3L1 levels [ Time Frame: From Baseline until end of study approximately 36 months ]
    Change in serum Chi3L1 levels at the EOS compared to baseline
Original Secondary Outcome Measures  ICMJE
 (submitted: May 28, 2020)
  • Time to onset of confirmed disability worsening confirmed over at least 6 months [ Time Frame: Up to approximately 36 months ]
    Time to onset of confirmed disability worsening (CDW), confirmed over at least 6 months, defined as follows:
    • increase of ≥1.5 points from the baseline expanded disability status scale (EDSS) score when the baseline score is 0 OR
    • increase of ≥1.0 point from the baseline EDSS score when the baseline score is 0.5 to ≤5.5 OR
    • increase of ≥0.5 point from the baseline EDSS score when the baseline score is >5.5 - 5.
  • Time to onset of CDW, assessed by the EDSS score and confirmed over at least 3 months [ Time Frame: Up to approximately 36 months ]
  • Total number of new and/or enlarging T2 hyperintense lesions as detected by MRI from Month 6 through the end of study (EOS) [ Time Frame: From 6 months up to approximately 36 months ]
  • Total of Gd-enhancing T1 hyperintense lesions as detected by MRI from 6 months through the EOS [ Time Frame: From 6 months up to approximately 36 months ]
  • Change in cognitive function [ Time Frame: From Baseline up to approximately 36 months ]
    Change in cognitive function from baseline to the end of study (EOS) as assessed by SDMT and by CVLT-II where available
  • Time to confirmed disability improvement [ Time Frame: From Baseline up to approximately 36 months ]
    Time to confirmed disability improvement (CDI), defined as a ≥1.0 point decrease on the EDSS from the baseline EDSS score confirmed over at least 6 months
  • Percent Change in Brain volume loss (BVL) [ Time Frame: From 6 months up to approximately 36 months ]
    Brain volume loss (BVL) rate as detected by brain MRI from Month 6 to the EOS
  • Change in Multiple Sclerosis Quality of Life [ Time Frame: From Baseline up to approximately 36 months ]
    Change in Multiple Sclerosis Quality of Life-54 (MSQoL-54) from the baseline through the EOS
  • Number of participants with adverse events A(Es) leading to permanent study intervention discontinuation, and adverse events of special interest (AESI) [ Time Frame: From screening until end of study approximately 36 months ]
  • Population Pharmacokinetics - Concentration SAR442168 at 6 months [ Time Frame: 6 Months ]
    Plasma concentration of SAR442168 (population PK assessment) at 6 Months
  • Population Pharmacokinetics Concentration of SAR442168 at 9 Months [ Time Frame: 9 Months ]
    Plasma concentration of SAR442168 (population PK assessment) at 9 Months
  • Population Pharmacokinetics - Concentration of SAR442168 at 12 Months [ Time Frame: 12 Months ]
    Plasma concentration of SAR442168 (population PK assessment) at 12 Months
  • Change in plasma NfL [ Time Frame: From Baseline until end of study approximately 36 months ]
    Change in plasma neurofilament light chain (NfL) levels at the EOS compared to baseline
  • Change in lymphocyte Phenotype [ Time Frame: From Baseline until end of study approximately 36 months ]
    Change in lymphocyte phenotype subsets in whole blood at the EOS compared to baseline
  • Changes in plasma Immunoglobulin levels [ Time Frame: From Baseline until end of study (up to 36 months) ]
    Changes in serum immunoglobulin level at the EOS compared to baseline
  • Change in CHI3L1 levels [ Time Frame: From Baseline until end of study approximately 36 months ]
    Change in serum Chi3L1 levels at the EOS compared to baseline
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Relapsing Forms of Multiple Sclerosis (RMS) Study of Bruton's Tyrosine Kinase (BTK) Inhibitor Tolebrutinib (SAR442168)
Official Title  ICMJE A Phase 3, Randomized, Double-blind Efficacy and Safety Study Comparing SAR442168 to Teriflunomide (Aubagio®) in Participants With Relapsing Forms of Multiple Sclerosis
Brief Summary

Primary Objective:

To assess efficacy of daily SAR442168 compared to a daily dose of 14 mg teriflunomide (Aubagio) measured by annualized adjudicated relapse rate (ARR) in participants with relapsing forms of MS

Secondary Objective:

To assess efficacy of SAR442168 compared to teriflunomide (Aubagio) on disability progression, MRI lesions, cognitive performance and quality of life To evaluate the safety and tolerability of daily SAR442168 To evaluate population pharmacokinetics (PK) of SAR442168 and relevant metabolites and its relationship to efficacy and safety To evaluate pharmacodynamics (PD) of SAR442168

Detailed Description Study duration will vary per participant in this event driven trial with a treatment duration of approximately 18 to 36 months. Participants completing the study will be offered to participate in a long term safety study.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Relapsing Multiple Sclerosis
Intervention  ICMJE
  • Drug: Tolebrutinib

    Pharmaceutical form: Tablet

    Route of administration: Oral

    Other Name: SAR442168
  • Drug: Teriflunomide HMR1726

    Pharmaceutical form: Tablet

    Route of administration: Oral

  • Drug: Placebo to match Tolebrutinib

    Pharmaceutical form: Tablet

    Route of administration: Oral

  • Drug: Placebo to match Teriflunomide

    Pharmaceutical form: Tablet

    Route of administration: Oral

Study Arms  ICMJE
  • Experimental: SAR442168
    Dose 1 of oral SAR442168 + placebo to match the teriflunomide tablet once daily
    Interventions:
    • Drug: Tolebrutinib
    • Drug: Placebo to match Teriflunomide
  • Active Comparator: Teriflunomide
    Oral 14 mg oral teriflunomide + placebo to match the SAR442168 tablet once daily
    Interventions:
    • Drug: Teriflunomide HMR1726
    • Drug: Placebo to match Tolebrutinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 28, 2020)
900
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 2023
Estimated Primary Completion Date August 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria :

  • The participant must be 18 to 55 years of age, inclusive, at the time of signing the informed consent
  • The participant must have been diagnosed with RMS according to the 2017 revision of the McDonald diagnostic criteria
  • The participant has an expanded disability status scale (EDSS) score ≤5.5 at the first Screening Visit
  • The participant must have at least 1 of the following prior to screening:

    • ≥1 documented relapse within the previous year OR
    • ≥2 documented relapses within the previous 2 years, OR
    • ≥1 documented Gd enhancing lesion on an MRI scan within the previous year
  • Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
  • Male participants are eligible to participate if they agree to the following during the intervention period and until accelerated elimination procedure:

    • Refrain from donating sperm

Plus either:

  • Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR
  • Must agree to use contraception/barrier as detailed below:

Agree to use a male condom and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak when having sexual intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant

  • A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions apply:

    • Is not a WOCBP OR
    • Is a WOCBP and agrees to use a contraceptive method that is highly effective (with a failure rate of <1% per year), preferably with low user dependency, during the intervention period and until accelerated elimination procedure is completed (or for at least 10 days after the last dose of SAR442168, if the case was unblinded)
  • A WOCBP must have a negative highly sensitive pregnancy test at screening and within 24hours before the first dose of study intervention.
  • If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
  • The Investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
  • The participant must have given written informed consent prior to undertaking any study related procedure. This includes consent to comply with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. In countries where the legal age of maturity is greater than 18 years, a specific ICF for such legally minor participants must also be signed by the participant's legally authorized representative

Exclusion criteria:

  • The participant has been diagnosed with primary progressive multiple sclerosis (PPMS) according to the 2017 revision of the McDonald diagnostic criteria or with nonrelapsing secondary progressive multiple sclerosis (SPMS)
  • The participant has a history of infection or may be at risk for infection including but not limited to: HIV, transplantation, live attenuated vaccines, progressive multifocal leukoencephalopathy, tuberculosis, hepatitis B or C, any persistent chronic or active recurring infection
  • Confirmed screening ALT >2 × ULN
  • The participant has conditions or situations that would adversely affect participation in this study, including but not limited to:

    • A short life expectancy due to pre-existing health condition(s) as determined by their treating neurologist
    • Medical condition(s) or concomitant disease(s) making them nonevaluable for the primary efficacy endpoint or that would adversely affect participation in this study, as judged by the Investigator
    • A requirement for concomitant treatment that could bias the primary evaluation
  • The participant has a history of or currently has concomitant medical or clinical conditions that would adversely affect participation in this study
  • At screening, the participant is positive for hepatitis B surface antigen and/or hepatitis B core antibody and/or is positive for hepatitis C antibody
  • The participant has any of the following:

    • A bleeding disorder or known platelet dysfunction at any time prior to the screening visit
    • A platelet count <150 000/μL at the screening visit
  • The participant has a lymphocyte count below the lower limit of normal (LLN) at the screening visit
  • The presence of psychiatric disturbance or substance abuse
  • Prior/concomitant therapy
  • The participant is receiving potent and moderate inducers of cytochrome P450 (CYP) 3A or potent inhibitors of CYP2C8 hepatic enzymes
  • The participant is receiving anticoagulant/antiplatelet therapies

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Trial Transparency email recommended (Toll free number for US & Canada) 800-633-1610 ext option 6 Contact-US@sanofi.com
Listed Location Countries  ICMJE Belarus,   Bulgaria,   Canada,   China,   Czechia,   Denmark,   Estonia,   Finland,   Germany,   Italy,   Japan,   Lithuania,   Poland,   Romania,   Russian Federation,   Spain,   Sweden,   Taiwan,   Turkey,   Ukraine,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04410978
Other Study ID Numbers  ICMJE EFC16033
U1111-1238-1418 ( Other Identifier: UTN )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://www.clinicalstudydatarequest.com/
Responsible Party Sanofi
Study Sponsor  ICMJE Sanofi
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Sciences & Operations Sanofi
PRS Account Sanofi
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP