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Nonrelapsing Secondary Progressive Multiple Sclerosis (NRSPMS) Study of Bruton's Tyrosine Kinase (BTK) Inhibitor SAR442168 (HERCULES)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04411641
Recruitment Status : Recruiting
First Posted : June 2, 2020
Last Update Posted : October 5, 2020
Sponsor:
Information provided by (Responsible Party):
Sanofi

Brief Summary:

Primary Objective:

To determine the efficacy of SAR442168 compared to placebo in delaying disability progression in NRSPMS

Secondary Objective:

To evaluate efficacy of SAR442168 compared to placebo on clinical endpoints, magnetic resonance imaging (MRI) lesions, cognitive performance, physical function, and quality of life To evaluate safety and tolerability of SAR442168 To evaluate population pharmacokinetics (PK) of SAR442168 and relevant metabolites in NRSPMS and its relationship to efficacy and safety To evaluate pharmacodynamics (PD) of SAR442168


Condition or disease Intervention/treatment Phase
Secondary Progressive Multiple Sclerosis Drug: SAR442168 Drug: Placebo to match SAR442168 Phase 3

Detailed Description:
Study duration will vary per participant in this event driven trial with a treatment duration of approximately 24 to 48 months. Participants completing the treatment period will be proposed to enroll in a separate Long term safety study.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1290 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-blind, Efficacy and Safety Study Comparing SAR442168 to Placebo in Participants With Nonrelapsing Secondary Progressive Multiple Sclerosis
Actual Study Start Date : September 24, 2020
Estimated Primary Completion Date : August 2024
Estimated Study Completion Date : August 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: SAR442168
Dose 1 of oral SAR442168 once daily
Drug: SAR442168
Pharmaceutical form: Film-coated tablet Route of administration: Oral

Placebo Comparator: Placebo
Placebo tablet to match SAR442168 once daily
Drug: Placebo to match SAR442168
Pharmaceutical form: Film-coated tablet Route of administration: Oral




Primary Outcome Measures :
  1. 6-month confirmed disability progression (CDP) [ Time Frame: Up to 48 approximately months ]

    Time to onset of 6 months CDP defined as follows:

    -Increase of ≥1.0 point from the baseline expanded disability status scale (EDSS) score when the baseline score is ≤5.0, or -Increase of ≥0.5 point when the baseline EDSS score is >5.0 -



Secondary Outcome Measures :
  1. 3-months change in T25-FW and 9-HPT [ Time Frame: Up to approximately 48 months ]
    Time to onset of composite CDP, confirmed over at least 3 months (3-month CCDP), by the EDSS Plus composite (EDSS score increase, or 20% increase in the T25 FW test, or 20% increase in the 9 hole peg test (9 HPT)

  2. 3-month CDP [ Time Frame: Up to approximately48 months ]
    Time to onset of 3-month CDP as assessed by EDSS score

  3. New and enlarging T2 hyperintense lesions by MRI [ Time Frame: From Baseline up to approximately 48 months ]
    Total number of new or enlarging T2 hyperintense lesions as detected by MRI

  4. Time to confirmed disability improvement (CDI) [ Time Frame: From Baseline up to approximately 48 months ]
    Time to CDI defined as ≥1.0 point decrease on the EDSS score from baseline confirmed over at least 6 months

  5. Brain volume loss (BVL) [ Time Frame: From 6 Months up to approximately 48 months ]
    Percent change in Brain volume loss (BVL) as detected by brain MRI at the EOS compared to month 6

  6. Change in cognitive function [ Time Frame: From Baseline up to approximately 48 months ]
    Change in cognitive function at the EOS compared to baseline as assessed by the Symbol Digit Modalities Test (SDMT) and by the California Verbal Learning Test (CVLT-II) -

  7. Change in Multiple Sclerosis Quality of Life-54 (MSQoL-54) [ Time Frame: From Baseline up to approximately 48 months ]
    Change in Multiple Sclerosis Quality of Life-54 (MSQoL-54) from the baseline through the EOS

  8. Safety and Tolerability [ Time Frame: From Screening until end of study up to approximately 48 months ]
    Number of participants with adverse events (AEs), Serious AEs, AEs leading to permanent study intervention discontinuation, and adverse events of special interest (AESI)

  9. Population pharmacokinetics [ Time Frame: Months 6, 9 and 12 ]
    Plasma concentration of SAR442168 and relevant metabolites (population PK assessment) at Months 6, 9, and 12

  10. Change in plasma neurofilament light chain (NfL) [ Time Frame: From Baseline up to approximately 48 months ]
    Change in NfL levels at the EOS compared to baseline -

  11. Changes in serum Immunoglobulin level [ Time Frame: From Baseline up to approximately 48 months ]
    Changes in serum Immunoglobulin level at the EOS compared to baseline

  12. Change in lymphocyte phenotype subsets [ Time Frame: From Baseline up to approximately 48 months ]
    Change in lymphocyte phenotype subsets in whole blood at the EOS compared to baseline

  13. Change in serum chitinase-3 like protein 1 (Chi3L1) [ Time Frame: From Baseline up to approximately 48 months ]
    Change in serum chitinase-3 like protein 1 (Chi3L1) at the EOS compared to baseline



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.


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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria :

  • 18 to 60 years of age inclusive
  • Diagnosis of nonrelapsing secondary progressive multiple sclerosis according to the 2017 McDonald criteria
  • Expanded disability status scale (EDSS) between 3.0 to 6.5 points inclusive, at screening
  • The participant must have documented evidence of disability progression observed during the 12 months before screening
  • Absence of clinical relapses for at least 24 months
  • The participant must have, at screening, disease duration from the onset of MS symptoms of:

    • <20 years in participants with EDSS scores at screening >5.0; OR
    • <10 years in participants with EDSS scores at screening ≤5.0
  • Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
  • A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:

    • Is not a WOCBP OR
    • Is a WOCBP and agrees to use an acceptable contraceptive method

Exclusion criteria:

  • The participant has conditions that would adversely affect study participation such as short life expectancy.
  • History of organ transplant.
  • Evidence of infection with human immuodeficiency virus (HIV), progressive multifocal leukoencephalopathy (PML), active hepatitis B or C, active or latent tuberculosis or other active infections that would adversely affect study participation.
  • History of malignancy within 5 years prior to screening.
  • History of alcohol or drug abuse within 1 year prior to screening.
  • Hospitalized for psychiatric disease within 2 years prior to screening.
  • Clinically significant laboratory abnormalities (including evidence of liver injury) or electrocardiogram abnormalities at screening
  • Bleeding disorder, known platelet dysfunction or platelet count <150 000/μL at screening.
  • A history of significant bleeding event within 6 months prior to screening, according to the Investigator's judgment such as, but not limited to cerebral or gastrointestinal bleeding.
  • Lymphocyte count below the lower limit of normal at screening.
  • Recent live (attenuated) vaccine within 2 months before the first treatment visit.
  • Recent major surgery (within 4 weeks of screening) or planned major surgery during the study.
  • The participant has received medications/treatments for MS within a specified time frame.
  • Receiving strong inducers or inhibitors of cytochrome P450 3A (CYP3A) or CYP2C8 hepatic enzymes.
  • Receiving anticoagulant or antiplatelet therapy (such as aspirin, clopidogrel, warfarin).
  • Contraindications to magnetic resonance imaging (MRI).

The above information is not intended to contain all considerations relevant to a patient'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): NCT04411641


Contacts
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Contact: Trial Transparency email recommended (Toll free number for US & Canada) 800-633-1610 ext option 6 Contact-US@sanofi.com

Locations
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United States, Florida
Investigational Site Number 8400029 Recruiting
Boca Raton, Florida, United States, 33487
Investigational Site Number 8400027 Recruiting
Naples, Florida, United States, 34105
Investigational Site Number 8400001 Recruiting
Tampa, Florida, United States, 33609-4052
Investigational Site Number 8400006 Recruiting
Tampa, Florida, United States, 33612
United States, Georgia
Investigational Site Number 8400003 Recruiting
Savannah, Georgia, United States, 31406
United States, Illinois
Investigational Site Number 8400011 Recruiting
Northbrook, Illinois, United States, 60062
United States, North Carolina
Investigational Site Number 8400005 Recruiting
Raleigh, North Carolina, United States, 27607
United States, Ohio
Investigational Site Number 8400010 Recruiting
Westerville, Ohio, United States, 40382
United States, South Carolina
Investigational Site Number 8400069 Recruiting
Greer, South Carolina, United States, 29650
United States, Tennessee
Investigational site number 8400087 Recruiting
Cordova, Tennessee, United States, 38018
Investigational Site Number 8400035 Recruiting
Franklin, Tennessee, United States, 37064
United States, Texas
Investigational Site Number 8400036 Recruiting
San Antonio, Texas, United States, 78258
Australia
Investigational Site Number 0360001 Recruiting
Fitzroy, Australia, 3065
Investigational Site Number 0360002 Recruiting
Kent Town, Australia
Bulgaria
Investigational site number 1000009 Recruiting
Sofia, Bulgaria, 1680
Canada
Investigational site number 1240006 Recruiting
Gatineau, Canada, J8Y 1W2
Sponsors and Collaborators
Sanofi
Investigators
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Study Director: Clinical Sciences & Operations Sanofi
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Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT04411641    
Other Study ID Numbers: EFC16645
U1111-1246-7768 ( Other Identifier: UTN )
First Posted: June 2, 2020    Key Record Dates
Last Update Posted: October 5, 2020
Last Verified: October 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/

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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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Neoplasm Metastasis
Multiple Sclerosis
Multiple Sclerosis, Chronic Progressive
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Neoplastic Processes
Neoplasms