E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028245 |
E.1.2 | Term | 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 determine the efficacy of SAR441344 as measured by reduction of the number of new active brain lesions |
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E.2.2 | Secondary objectives of the trial |
• To evaluate efficacy of SAR441344 on disease activity as assessed by other MRI measures
• To evaluate the safety and tolerability of SAR441344
• To evaluate pharmacokinetics of SAR441344 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
I 01. Participant must be 18 to 55 years of age inclusive, at the time of signing the informed consent.
I 02. The participant must have been diagnosed with RMS (relapsing-remitting MS and secondary progressive MS participants with relapses) according to the 2017 revision of the McDonald diagnostic criteria.
I 03. The participant must have at least 1 documented relapse within the previous year, or ≥2 documented relapses within the previous 2 years, or ≥1 active Gd-enhancing brain lesion on an MRI scan in the past 6 months and prior to screening.
I 04. Body weight within 45 to 120 kg (inclusive) and body mass index (BMI) within the range 18.0 to 35.0 kg/m2 (inclusive) at Screening.
I 05. Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
I 06. Capable of giving signed informed consent.
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E.4 | Principal exclusion criteria |
E 01. The participant has been diagnosed with PPMS according to the 2017 revision of the McDonald diagnostic criteria or with non-relapsing SPMS.
E 02. The participant has conditions or situations that would adversely affect participation in this study.
E 03. The participant has a history of or currently has concomitant medical or clinical conditions that would adversely affect participation in this study.
E 04. History, clinical evidence, suspicion or significant risk for thromboembolic events, as well as myocardial infarction, stroke and/or antiphosholipid syndrome and any participants requiring antithrombotic treatment.
E 05. Allergies to humanized monoclonal antibodies, intolerance to topical corticosteroids, or severe post-treatment hypersensitivity reactions other than localized injection site reaction, to any biological molecule.
E 06. The participant has received any of the forbidden medications/treatments within the specified time frame before any baseline assessment.
E 07. The participant has taken other investigational drug within 3 months or 5-halflive, whichever is longer, before the screening visit.
E 08. The participant has an EDSS score >5.5 at the first screening visit.
E 09. The participant has had a relapse in the 30 days prior to randomization.
E 10. Positive human immunodeficiency virus (HIV) serology (anti HIV1 and anti HIV2 antibodies) or a known history of HIV infection, active or in remission.
E 11. Abnormal laboratory test(s) at Screening.
E 12. Presence of Hepatitis B surface antigen (HBsAg) or anti-Hepatitis B core antibodies (antiHBc Ab) at screening or within 3 months prior to first dose of study intervention.
E 13. Positive Hepatitis C antibody test result at screening or within 3 months prior to starting study intervention. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Number of new Gadolinium (Gd)-enhancing T1hyperintense (GdE T1) lesions : measured by brain magnetic resonance imaging (MRI) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1/ Number of new or enlarging T2 lesions: measured by brain magnetic resonance imaging (MRI)
2/ Total number of GdE T1 lesions: Total number of GdE T1 lesions at Week 12
3/ Adverse events (AEs) and serious adverse events (SAEs): Number of participants with AEs and SAEs
4/Antidrug antibodies (ADA): Number of participants with ADA
5/ Pharmacokinetic (PK) parameters: Cmax: maximum concentration
6/ PK parameter: tmax: time to Cmax
7/ PK parameter: AUC0-tau: area under the curve over the dosing interval
8/ PK parameter: t1/2z: elimination halflife
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1/ and 2/: at Week 12 3/ to 8/: Until Week 88 |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
Part A=12week, double-blind, placebo-controlled part; Part B=open-label SAR441344 treatment part |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 26 |
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 |
Canada |
Russian Federation |
Turkey |
United States |
Bulgaria |
France |
Germany |
Spain |
Czechia |
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E.8.7 | Trial has a data monitoring committee | No |
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 |