Dose-finding Study for SAR442168 in Relapsing Multiple Sclerosis
|
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. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT03889639 |
|
Recruitment Status :
Completed
First Posted : March 26, 2019
Results First Posted : March 8, 2023
Last Update Posted : March 8, 2023
|
Sponsor:
Sanofi
Information provided by (Responsible Party):
Sanofi
- Study Details
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
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.
|
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 :
- Brain Magnetic Resonance Imaging (MRI) Assessment: Number of New Gadolinium (Gd) Enhancing T1-hyperintense Lesions [ Time Frame: After 12 weeks of SAR442168 treatment for SAR442168 reporting arms (i.e., at Week 12 for Cohort 1 participants, at Week 16 for Cohort 2 participants) and at Week 4 for Cohort 2 placebo ]Number of new Gd-enhancing T1-hyperintense lesions was detected by brain MRI at the end of 12 weeks of SAR442168 treatment (i.e., at Week 12 for Cohort 1 participants and Week 16 for Cohort 2 participants). Data was planned to be collected and analyzed on pooled population of participants at each dose level of SAR442168 (either in Cohort 1 and 2) and pooled population of participants receiving placebo in Cohort 2 and was not planned to collected during placebo administration in Cohort 1 (Weeks 12 to 16).
Secondary Outcome Measures :
- Number of New or Enlarging T2 Lesions [ Time Frame: After 12 weeks of SAR442168 treatment for SAR442168 reporting arms (i.e., at Week 12 for Cohort 1 participants, at Week 16 for Cohort 2 participants), and at Week 4 for Cohort 2 placebo ]Number of new and enlarging T2 lesions was detected by brain MRI at the end of 12 weeks of SAR442168 treatment (i.e., at Week 12 for Cohort 1 participants and Week 16 for Cohort 2 participants).
- Total Number of Gd-enhancing T1-hyperintense Lesions [ Time Frame: After 12 weeks of SAR442168 treatment for SAR442168 reporting arms (i.e., at Week 12 for Cohort 1 participants, at Week 16 for Cohort 2 participants), and at Week 4 for Cohort 2 placebo ]Total number of Gd-enhancing T1-hyperintense lesions was detected by brain MRI at the end of 12 weeks of SAR442168 treatment (i.e., at Week 12 for Cohort 1 participants and Week 16 for Cohort 2 participants).
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs): Weeks 1-4 Period [ Time Frame: From Baseline up to Week 4 ]Adverse event (AE) was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with use of study drug. Serious AE (SAE) was defined as any untoward medical occurrence that, at any dose resulted in death, life-threatening, inpatient hospitalization or prolongation of existing hospitalization, disability/incapacity, congenital anomaly/birth defect, or medical event. TEAEs were defined as AEs (serious/non-serious) that developed, worsened, or became serious during on-treatment period (for this outcome measure- "Weeks 1 to 4 period": time from 1st administration of study drug to Week 4). Cohorts 1 and 2 received SAR442168 and placebo for first 4 weeks, respectively.
- Number of Participants With Treatment-emergent Adverse Events and Treatment-emergent Serious Adverse Events: SAR442168 Treatment Period [ Time Frame: Weeks 1 to 12 for Cohort 1 participants and Weeks 4 to 16 for Cohort 2 participants ]AE was defined as any unfavorable and unintended sign (including abnormal laboratory finding), symptom, or disease temporally associated with use of study drug. SAE was defined as any untoward medical occurrence that, at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, persistent disability/incapacity, congenital anomaly/birth defect, or medical event. TEAEs: AEs that developed, worsened, or became serious during on-treatment period (for this outcome measure defined as "SAR442168 treatment period" which was considered as Weeks 1 to 12 for Cohort 1 and Weeks 4 to 16 for Cohort 2).
- Number of Participants With Individual Clinically Relevant Abnormalities in Laboratory Tests (Hematology, Chemistry, Urinalysis), Vital Signs, and Electrocardiograms (ECG) [ Time Frame: Baseline up to Week 12 for Cohort 1 participants; Baseline up to Week 4 for Cohort 2 Placebo and from Weeks 4 to 16 for Cohort 2 SAR442168 receiving participants ]Individual clinically relevant abnormalities was defined as potentially clinically significant abnormalities (PCSA) considered as SAEs or TEAEs leading to study treatment discontinuation or study discontinuation during the on-treatment period (time from first study drug administration until Week 16), considering all evaluations performed during the on-treatment period that included unscheduled or repeated evaluations.
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| 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 |
Study Documents (Full-Text)
Documents provided by Sanofi:
Documents provided by Sanofi:
Study Protocol [PDF] April 9, 2019
Statistical Analysis Plan [PDF] October 25, 2019
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| 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 |
| Results First Posted: | March 8, 2023 |
| Last Update Posted: | March 8, 2023 |
| Last Verified: | March 2023 |
| 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://vivli.org |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
|
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 |