E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsing Multiple Sclerosis |
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E.1.1.1 | Medical condition in easily understood language |
Relapsing Multiple Sclerosis |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10080700 |
E.1.2 | Term | Relapsing multiple sclerosis |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 |
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E.2.2 | Secondary objectives of the trial |
- 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 pharmacodynamics (PD) of SAR442168
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 criter - 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 Woman of child-bearing ptential (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 24 hours 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 |
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E.4 | Principal exclusion criteria |
- The participant has been diagnosed with primary progressive multiplesclerosis (PPMS) according to the 2017 revision of the McDonald diagnostic criteria or with nonrelapsing secondary progressive multiplesclerosis (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 - 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Annualized Adjudicated Relapse Rate : Number of confirmed protocol defined relapses ; Annualized Adjudicated Relapse Rate : Number of confirmed protocol defined adjudicated relapses |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up to approximately 36 months |
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E.5.2 | Secondary end point(s) |
1 - Time to onset of confirmed disability worsening confirmed over at least 6 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 2 - Time to onset of CDW, assessed by the EDSS score and confirmed over at least 3 month 3 - Total number of new and/or enlarging T2 hyperintense lesions as detected by MRI from Month 6 through the end of study 4 - Total of Gd-enhancing T1 hyperintense lesions as detected by MRI from 6 months through the EOS 5 - Change in cognitive function ; Change in cognitive function from baseline to the EOS as assessed by SDMTand by CVLT-II where available 6 - Time to confirmed disability improvement ; 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 7 - Percent Change in Brain volume loss (BVL) ; Brain volume loss (BVL) rate as detected by brain MRI from Month 6 to the EOS 8 - Change in Multiple Sclerosis Quality of Life ; Change in Multiple Sclerosis Quality of Life-54 (MSQoL-54) from the baseline through the EOS 9 - Number of participants with adverse events (AEs) leading to permanent study intervention discontinuation, and adverse events of special interest (AESI) 10 - Change in plasma neurofilament light chain (NfL) ; Change in plasma neurofilament light chain (NfL) levels at the EOS compared to baselineC 11 - Changes in plasma Immunoglobulin level ; Changes in serum immunoglobulin level at the EOS compared to baseline 12 - Change in serum chitinase-3 like protein 1 (Chi3L1) ; Change in serum Chi3L1 levels at the EOS compared to baseline |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1, 2 - Up to approximately 36 months 3, 4, 7 : From 6 months up to approximately 36 months 5, 6, 8 : From Baseline up to approximately 36 months 9 - From screening until end of study approximately 36 months 10, 11, 12 : From Baseline until end of study up to approximately 36 months |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 65 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Brazil |
Canada |
Chile |
India |
Israel |
Korea, Republic of |
United States |
France |
Latvia |
Netherlands |
Spain |
Switzerland |
Czechia |
Germany |
Greece |
Belgium |
Croatia |
Hungary |
Norway |
Portugal |
Russian Federation |
Serbia |
Slovakia |
Turkey |
Ukraine |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |