Dose-finding Study for SAR442168 in Relapsing Multiple Sclerosis

Sanofi

Status and phase: Completed; Phase 2

Conditions: Relapsing Multiple Sclerosis

Treatments: Drug: SAR442168; Drug: Placebo; Drug: Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI)

Study type: Interventional

Funder types: Industry

Identifiers

NCT03889639

2018-003927-12 (EudraCT Number)

U1111-1220-0572 (Other Identifier)

DRI15928

Details and patient eligibility

About

Primary Objective:

To determine the dose-response relationship for SAR442168 to reduce the number of new active brain lesions.

Secondary Objectives:

• To evaluate efficacy of SAR442168 on disease activity as assessed by imaging measures.
• To evaluate the safety and tolerability of SAR442168.

Full description

The total study duration was 24 weeks which included a screening period of 4 weeks, a treatment period of 16 weeks, and a follow-up period of up to 4 weeks. Participants who completed the Week 16 visit were proposed to be enrolled in a long-term extension safety and efficacy study to assess safety, tolerability and efficacy of SAR442168.

Enrollment: 130 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participant must be 18 to 55 years of age, inclusive, at the time of signing the informed consent.
• Participant was diagnosed with relapsing multiple sclerosis (RMS) according to the 2017 revision of the McDonald diagnostic criteria.
• Participant must had at least 1 documented relapse within the previous year, OR greater than or equal to (>=) 2 documented relapses within the previous 2 years, OR >=1 active Gadolinium (Gd) enhancing brain lesion on an MRI scan in the past 6 months and prior to screening.
• A female participant must had used a double contraception method including a highly effective method of birth control from inclusion and up to 2 months after the last study dose, except if she had undergone sterilization at least 3 months earlier or was postmenopausal. Menopause was defined as being amenorrheic for >=12 months with serum follicle-stimulating hormone (FSH) level greater than (>) 30 International Units per liters.
• Male participants, whose partners were of childbearing potential (including breastfeeding women), must had accepted to use, during sexual intercourse, a double contraceptive method according to the following algorithm: (condom) plus (intrauterine device or hormonal contraceptive) from inclusion up to 3 months after the last dose.
• Male participants whose partners were pregnant must had used, during sexual intercourse, a condom from inclusion up to 3 months after the last dose.
• Male participants had agreed not to donate sperm from the inclusion up to 3 months after the last dose.
• Participant had given written informed consent prior to undertaking any study-related procedure.

Exclusion criteria

• The participant had been diagnosed with primary progressive multiple sclerosis according to the 2017 revision of the McDonald diagnostic criteria or with non relapsing secondary progressive multiple sclerosis.
• Requirement for concomitant treatment that could bias the primary evaluation.
• Contraindication for MRI.
• Contraindications to use MRI Gd contrast-enhancing preparations.
• History of infection with the human immunodeficiency virus (HIV).
• History of active or latent tuberculosis.
• Any other active infections that would adversely affect participation or investigational medicinal product administration in this study, as judged by the Investigator.
• Presence of any screening laboratory or electrocardiogram values outside normal limits that were considered in the Investigator's judgment to be clinically significant.
• Presence of liver injury.
• At screening, the participant was positive for hepatitis B surface antigen and/or hepatitis B core antibody and/or was positive for hepatitis C antibody.
• Bleeding disorder or known platelet dysfunction at any time prior to screening visit.
• Participant had received any live (attenuated) vaccine (including but not limited to varicella zoster, oral polio, and nasal influenza) within 2 months before first treatment visit.
• Participant was receiving strong inducers or inhibitors of cytochrome P450 3A (CYP3A) or CYP2C8 hepatic enzymes.
• Participant was receiving anticoagulant/antiplatelet therapies.
• Participant had taken other investigational drugs within 3 months or 5 half lives, whichever was longer, before screening visit.
• Participant had an Expanded Disability Status Scale score >5.5 at first screening visit.
• Participant had a relapse in the 30 days prior to randomization.
• Participant was pregnant or a breastfeeding woman.
• History or presence of significant other concomitant illness.
• The participant had received medications/treatments for multiple sclerosis within a specified time frame.

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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130 participants in 8 patient groups

Cohort 1: SAR442168 5 mg Then Placebo

Experimental group

Description:

Participants received SAR442168 5 milligrams (mg), orally once daily for first 12 weeks then crossed over to matching placebo orally once daily for 4 weeks during the 16 weeks treatment period. To maintain the blinding, each participant was given a total of 4 tablets daily, either of SAR442168 or SAR442168 and placebo, to achieve the specified daily dose of SAR442168.

Treatment:

Drug: Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI)

Drug: Placebo

Drug: SAR442168

Cohort 1: SAR442168 15 mg Then Placebo

Experimental group

Description:

Participants received SAR442168 15 mg, orally once daily for first 12 weeks then crossed over to matching placebo orally once daily for 4 weeks during the 16 weeks treatment period. To maintain the blinding, each participant was given a total of 4 tablets daily, either of SAR442168 or SAR442168 and placebo, to achieve the specified daily dose of SAR442168.

Treatment:

Drug: Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI)

Drug: Placebo

Drug: SAR442168

Cohort 1: SAR442168 30 mg Then Placebo

Experimental group

Description:

Participants received SAR442168 30 mg, orally once daily for first 12 weeks then crossed over to matching placebo orally once daily for 4 weeks during the 16 weeks treatment period. To maintain the blinding, each participant was given a total of 4 tablets daily, either of SAR442168 or SAR442168 and placebo, to achieve the specified daily dose of SAR442168.

Treatment:

Drug: Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI)

Drug: Placebo

Drug: SAR442168

Cohort 1: SAR442168 60 mg Then Placebo

Experimental group

Description:

Participants received SAR442168 60 mg, orally once daily for first 12 weeks then crossed over to matching placebo orally once daily for 4 weeks during the 16 weeks treatment period. To maintain the blinding, each participant was given a total of 4 tablets daily, either of SAR442168 or SAR442168 and placebo, to achieve the specified daily dose of SAR442168.

Treatment:

Drug: Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI)

Drug: Placebo

Drug: SAR442168

Cohort 2: Placebo Then SAR442168 5 mg

Experimental group

Description:

Participants received placebo matching to SAR442168 tablets, orally once daily for first 4 weeks then crossed over to SAR442168 5 mg orally once daily for 12 weeks during the 16 weeks treatment period. To maintain the blinding, each participant was given a total of 4 tablets daily, either of SAR442168 or SAR442168 and placebo, to achieve the specified daily dose of SAR442168.

Treatment:

Drug: Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI)

Drug: Placebo

Drug: SAR442168

Cohort 2: Placebo Then SAR442168 15 mg

Experimental group

Description:

Participants received placebo matching to SAR442168 tablets, orally once daily for first 4 weeks then crossed over to SAR442168 15 mg orally once daily for 12 weeks during the 16 weeks treatment period. To maintain the blinding, each participant was given a total of 4 tablets daily, either of SAR442168 or SAR442168 and placebo, to achieve the specified daily dose of SAR442168.

Treatment:

Drug: Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI)

Drug: Placebo

Drug: SAR442168

Cohort 2: Placebo Then SAR442168 30 mg

Experimental group

Description:

Participants received placebo matching to SAR442168 tablets, orally once daily for first 4 weeks then crossed over to SAR442168 30 mg orally once daily for 12 weeks during the 16 weeks treatment period. To maintain the blinding, each participant was given a total of 4 tablets daily, either of SAR442168 or SAR442168 and placebo, to achieve the specified daily dose of SAR442168.

Treatment:

Drug: Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI)

Drug: Placebo

Drug: SAR442168

Cohort 2: Placebo Then SAR442168 60 mg

Experimental group

Description:

Participants received placebo matching to SAR442168 tablets, orally once daily for first 4 weeks then crossed over to SAR442168 60 mg orally once daily for 12 weeks during the 16 weeks treatment period. To maintain the blinding, each participant was given a total of 4 tablets daily, either of SAR442168 or SAR442168 and placebo, to achieve the specified daily dose of SAR442168.

Treatment:

Drug: Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI)

Drug: Placebo

Drug: SAR442168