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Primary Progressive Multiple Sclerosis (PPMS) Study of Bruton's Tyrosine Kinase (BTK) Inhibitor SAR442168 (PERSEUS) (PERSEUS)

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: NCT04458051
Recruitment Status : Recruiting
First Posted : July 7, 2020
Last Update Posted : October 14, 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 primary progressive multiple sclerosis (PPMS)

Secondary Objectives:

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 in PPMS and its relationship to efficacy and safety To evaluate pharmacodynamics of SAR442168


Condition or disease Intervention/treatment Phase
Primary Progressive Multiple Sclerosis Drug: SAR442168 Drug: Placebo 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 990 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 Primary Progressive Multiple Sclerosis (PERSEUS)
Actual Study Start Date : August 13, 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 daily
Drug: SAR442168
Pharmaceutical form: Film-coated Tablet Route of administration: Oral

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




Primary Outcome Measures :
  1. 6 month Confirmed Disability Progression (CDP) [ Time Frame: Up to approximately 48 months ]

    Time to onset of 6 month CDP defined as follows:

    Increase of ≥1.0 point from the baseline expanded disability status scale (EDSS) score when the baseline score is ≤5.5, or Increase of ≥0.5 points when the baseline EDSS score is >5.5



Secondary Outcome Measures :
  1. 3-month confirmed disability progression (CDP) [ Time Frame: Up to approximately 48 months ]
    Time to onset of 3-month CDP as assessed by EDSS score

  2. 3-month change in 9-hole peg test (9-HPT) [ Time Frame: Up to approximately 48 months ]
    Time to onset of sustained 20% increase in the 9-HPT test confirmed over at least 3 months

  3. 3-month change in timed 25 foot walk (T25-FW) [ Time Frame: Up to approximately 48 months ]
    Time to onset of sustained 20% increase in the T25-FW confirmed over at least 3 months

  4. Change in T2 hyperintense lesions by MRI [ Time Frame: From Baseline up to 48 approximately months ]
    Total number of new and/or enlarging T2 hyperintense lesions as detected by MRI after baseline up to and including the end of study (EOS)

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

  6. Percent change in 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

  7. Change in cognitive function as assessed by the Symbol Digit Modalities Test (SDMT) [ Time Frame: From Baseline up to approximately 48 months ]
    Change in cognitive function at the EOS compared to baseline as assessed by the SDMT

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

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

  10. Safety and Tolerability [ Time Frame: From screening 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)

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

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

  13. 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

  14. 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

  15. 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) from baseline to EOS



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 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria :

  • 18 to 55 years of age inclusive
  • Diagnosis of PPMS according to the 2017 McDonald criteria
  • Expanded disability status scale (EDSS) between 2.0 to 6.5 points, inclusive at screening
  • Disease duration from the onset of MS symptoms of <15 years if screening EDSS score of >5.0 OR <10 years if screening EDSS score of ≤5.0.
  • Positive cerebrospinal fluid oligoclonal bands and/or elevated Immunoglobulin G (IgG) index either during screening or documented previous history.
  • Contraceptive use consistent with local regulations for individuals participating in clinical studies

Exclusion criteria:

  • Participant has conditions that would adversely affect study participation such as short life expectancy.
  • History of organ transplant.
  • Evidence of infection with human immunodeficiency virus (HIV), progressive multifocal leukoencephalopathy (PML), active hepatitis B or C, active or latent tuberculosis or other active infection 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.
  • 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): NCT04458051


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, California
Investigational Site Number 8400045 Recruiting
Long Beach, California, United States, 90806
Investigational Site Number 8400088 Recruiting
Torrance, California, United States, 90502
United States, Colorado
Investigational Site Number 8400025 Recruiting
Fort Collins, Colorado, United States, 80528
United States, Florida
Investigational Site Number 8400029 Recruiting
Boca Raton, Florida, United States, 33487
Investigational Site Number 8400004 Recruiting
Maitland, Florida, United States, 32761
Investigational Site Number 8400006 Recruiting
Tampa, Florida, United States, 33612
United States, Illinois
Investigational Site Number 8400071 Recruiting
Springfield, Illinois, United States, 62701
United States, North Carolina
Investigational Site Number 8400005 Recruiting
Raleigh, North Carolina, United States, 27607
United States, Ohio
Investigational Site Number 8400147 Recruiting
Columbus, Ohio, United States, 43235
United States, Tennessee
Investigational Site Number 8400035 Recruiting
Franklin, Tennessee, United States, 37064
United States, Washington
Investigational Site Number 8400099 Recruiting
Spokane, Washington, United States, 99202
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: NCT04458051    
Other Study ID Numbers: EFC16035
U1111-1238-1318 ( Other Identifier: UTN )
First Posted: July 7, 2020    Key Record Dates
Last Update Posted: October 14, 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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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