Dose-finding Study for SAR442168 in Relapsing Multiple Sclerosis
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| ClinicalTrials.gov Identifier: NCT03889639 |
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Recruitment Status :
Completed
First Posted : March 26, 2019
Last Update Posted : January 25, 2021
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Sponsor:
Sanofi
Information provided by (Responsible Party):
Sanofi
- Study Details
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Brief Summary:
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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Relapsing Multiple Sclerosis | Drug: SAR442168 Drug: Placebo Drug: Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI) | Phase 2 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 130 participants |
| Allocation: | Randomized |
| Intervention Model: | Crossover Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 2b Dose-finding Study for SAR442168, a Bruton's Tyrosine Kinase Inhibitor, in Participants With Relapsing Multiple Sclerosis |
| Actual Study Start Date : | March 29, 2019 |
| Actual Primary Completion Date : | January 2, 2020 |
| Actual Study Completion Date : | January 2, 2020 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Multiple sclerosis
MedlinePlus related topics:
Multiple Sclerosis
| Arm | Intervention/treatment |
|---|---|
|
Experimental: Cohort 1: SAR442168 5 mg Then Placebo
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.
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Drug: SAR442168
Pharmaceutical form: Film coated tablet; Route of administration: Oral Drug: Placebo Pharmaceutical form: Film coated tablet; Route of administration: Oral Drug: Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI) Pharmaceutical form: Solution for injection; Route of administration: Intravenous |
|
Experimental: Cohort 1: SAR442168 15 mg Then Placebo
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.
|
Drug: SAR442168
Pharmaceutical form: Film coated tablet; Route of administration: Oral Drug: Placebo Pharmaceutical form: Film coated tablet; Route of administration: Oral Drug: Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI) Pharmaceutical form: Solution for injection; Route of administration: Intravenous |
|
Experimental: Cohort 1: SAR442168 30 mg Then Placebo
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.
|
Drug: SAR442168
Pharmaceutical form: Film coated tablet; Route of administration: Oral Drug: Placebo Pharmaceutical form: Film coated tablet; Route of administration: Oral Drug: Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI) Pharmaceutical form: Solution for injection; Route of administration: Intravenous |
|
Experimental: Cohort 1: SAR442168 60 mg Then Placebo
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.
|
Drug: SAR442168
Pharmaceutical form: Film coated tablet; Route of administration: Oral Drug: Placebo Pharmaceutical form: Film coated tablet; Route of administration: Oral Drug: Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI) Pharmaceutical form: Solution for injection; Route of administration: Intravenous |
|
Experimental: Cohort 2: Placebo Then SAR442168 5 mg
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.
|
Drug: SAR442168
Pharmaceutical form: Film coated tablet; Route of administration: Oral Drug: Placebo Pharmaceutical form: Film coated tablet; Route of administration: Oral Drug: Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI) Pharmaceutical form: Solution for injection; Route of administration: Intravenous |
|
Experimental: Cohort 2: Placebo Then SAR442168 15 mg
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.
|
Drug: SAR442168
Pharmaceutical form: Film coated tablet; Route of administration: Oral Drug: Placebo Pharmaceutical form: Film coated tablet; Route of administration: Oral Drug: Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI) Pharmaceutical form: Solution for injection; Route of administration: Intravenous |
|
Experimental: Cohort 2: Placebo Then SAR442168 30 mg
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.
|
Drug: SAR442168
Pharmaceutical form: Film coated tablet; Route of administration: Oral Drug: Placebo Pharmaceutical form: Film coated tablet; Route of administration: Oral Drug: Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI) Pharmaceutical form: Solution for injection; Route of administration: Intravenous |
|
Experimental: Cohort 2: Placebo Then SAR442168 60 mg
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.
|
Drug: SAR442168
Pharmaceutical form: Film coated tablet; Route of administration: Oral Drug: Placebo Pharmaceutical form: Film coated tablet; Route of administration: Oral Drug: Locally approved intravenous contrast medium for contrast enhanced magnetic resonance imaging (MRI) Pharmaceutical form: Solution for injection; Route of administration: Intravenous |
Primary Outcome Measures :
- Number of new Gd-enhancing T1 hyperintense lesions [ Time Frame: Week 12 for Arms 1 - 4, Week 4 and Week 16 for Arms 5 - 8 ]Number of new Gd-enhancing T1 hyperintense lesions at the end of 12 weeks of SAR442168 treatment as detected by brain MRI
Secondary Outcome Measures :
- Number of new or enlarging T2 lesions [ Time Frame: Week 12 for Arms 1 - 4, Week 4 and Week 16 for Arms 5 - 8 ]Number of new or enlarging T2 lesions at the end of 12 weeks of SAR442168 treatment
- Total number of Gd-enhancing T1 hyperintense lesions [ Time Frame: Week 12 for Arms 1 - 4, Week 4 and Week 16 for Arms 5 - 8 ]Total number of Gd-enhancing T1-hyperintense lesions at the end of 12 weeks of SAR442168 treatment
- Number of participants experiencing adverse events [ Time Frame: From baseline to the end of study (approximately 20 weeks) ]Number (n) of participants experiencing an adverse event (AE)/Serious Adverse Event (SAE) or potentially clinically significant abnormalities in laboratory tests, electrocardiogram (ECG), or vital signs
- Percentage of participants experiencing adverse events [ Time Frame: From baseline to the end of study (approximately 20 weeks) ]Percentage (%) of participants experiencing an adverse event (AE)/Serious Adverse Event (SAE) or potentially clinically significant abnormalities in laboratory tests, electrocardiogram (ECG), or vital signs
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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:
- 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.
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): NCT03889639
Locations
Show 48 study locations
Sponsors and Collaborators
Sanofi
Investigators
| Study Director: | Clinical Sciences & Operations | Sanofi |
| Responsible Party: | Sanofi |
| ClinicalTrials.gov Identifier: | NCT03889639 |
| Other Study ID Numbers: |
DRI15928 2018-003927-12 ( EudraCT Number ) U1111-1220-0572 ( Other Identifier: UTN ) |
| First Posted: | March 26, 2019 Key Record Dates |
| Last Update Posted: | January 25, 2021 |
| Last Verified: | December 2020 |
| Individual Participant Data (IPD) Sharing Statement: | |
| 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/ |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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 |