Primary progressive multiple sclerosis (PPMS) study of BTK inhibitor SAR442168 (PERSEUS)
- Conditions
- Multiple sclerosis,
- Registration Number
- CTRI/2020/10/028392
- Lead Sponsor
- Sanofi Healthcare India Private Limited
- Brief Summary
SAR442168 is expected to reduce MS relapse rate,disability progression, and underlying central nervous system (CNS) damagethrough its dual action on adaptive immunity in the periphery and innate immunityand the inflammation process in the CNS. The results from the Phase 2b trial(DRI15928) demonstrated a dose–response relationshipfor SAR442168 as evidenced by a reduction in the number of new Gd-enhancingT1-hyperintense brain lesions detected by brain MRI after 12 weeks oftreatment. There was an 85% relative reduction in lesions at 12 weeks in the 60mg dose group as compared with placebo. This was obtained from the negativebinomial regression model adjusted for baseline Gd-enhancing T1-hyperintenselesion activity.
PPMS accounts forapproximately 10 to 15 percent all patients with MS. In general, chronic disability accumulation remains a significantunmet need for people living with MS. Individuals with progressive MS needtherapies to reduce the accumulation of disability. There is no approvedtreatment for PPMS in India. Evidenceof inflammation and presence of activated T and B cells in the brain have beenconfirmed in PPMS, especially in the early stages.4 However,immunomodulatory therapies have shown very little effect on disease activity inthese patients. Even the most recent high-efficacy immunomodulatory agents actmainly on adaptive immunity in the periphery with only modest or temporaryability to slow neuroinflammatory and neurodegenerative processes and stopdisease progression. 5,6 As mentioned above, this may relate toconditions in the CNS, especially the integrity of the blood-brainbarrier, but also to the potency and mechanism ofaction of the agents.
Thus, there is still a significantunmet need for therapies with new modes of action that target neuroinflammationin the CNS with a goal of halting long-term disability and neurodegeneration inall categories of MS including PPMS
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Open to Recruitment
- Sex
- All
- Target Recruitment
- 900
- Participants are eligible to be included in the study only if all of the following criteria apply: Age: I 01. The participant must be 18 to 55 years of age, inclusive, at the time of signing the informed consent Type of participant and disease characteristics: I 02. The participant must have been diagnosed with PPMS in according with the 2017 revision of the McDonald diagnostic criteria I 03. The participant must have an EDSS score at screening from 2.0 to 6.5 points, inclusive. I 04. The participant must have, at screening, disease duration from the onset of MS symptoms of:.
- <15 years in participants with EDSS scores at screening >5.0, OR.
- <10 years in participants with EDSS scores at screening ≤5.0 I 05. The participant must have positive CSF (isoelectric focusing evidence of oligoclonal bands and/or elevated IgG index) either during screening or previous historical assessment. Supportive source documentation must be available. Weight I 06. Not applicable. Sex I 07. Male or female Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. A) Male participants Not applicable B) Female participants 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 woman of childbearing potential (WOCBP) OR Is a WOCBP and agrees to use an acceptable contraceptive method as described in Appendix 4 of protocol during the intervention period. A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) (Appendix 2 [Section 10.2] of protocol) before the first dose of study intervention. If a urne test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. Requirements for pregnancy testing during and after study intervention are located in the schedule of activities (SoA; Section 1.3 of the protocol). Additional requirements for pregnancy testing during and after study intervention are located in Appendix 2 (Section 10.2 of the protocol). The Investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy, if allowed by local regulations. See Appendix 9 (Section 10.9) for country-specific contraception requirements. Informed Consent I 08. The participant must have given written informed consent prior to undertaking any study related procedure. This includes consent to comply with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. In countries where the legal age of maturity is greater than 18 years, a specific ICF for such legally minor participants must also be signed by the participant’s legally authorized representative (Appendix 1, Section 10.1.3).
- Participants are excluded from the study if any of the following criteria apply: Medical conditions E 01.
- The participant has a history of infection or may be at risk for infection: A history of T-lymphocyte or T-lymphocyte-receptor vaccination, transplantation (including solid organ, stem cell, and bone marrow transplantation) and/or antirejection therapy E 02.
- The presence of psychiatric disturbance or substance abuse as evidenced by: A history of any psychiatric disease, behavioral condition, or depression requiring hospitalization within 2 years prior to the Screening Visit E 03.
- The following findings obtained during the screening visit considered in the Investigator’s judgment to be clinically significant: Any screening laboratory values outside normal limits.
- Abnormal ECG E 04.
- Conditions that may predispose the patient to excessive bleeding: A bleeding disorder or known platelet dysfunction at any time prior to the Screening Visit.
- A platelet count <150 000/μL at the Screening Visit.
- The participant has had major surgery within 4 weeks prior to the Screening Visit, which could affect the participant’s safety or affect immune response (as judged by the Investigator) or has planned any elective major surgery during the study.
- Prior/concomitant therapy E 06.
- A requirement for concomitant treatment that could bias the primary evaluation, such as any of the following medications/treatments within the specified time frame before any randomization assessment (no wash out is required for interferon beta or glatiramer acetate treatments although use is not permitted on or after Day 1 E 07.
- The participant is receiving strong inducers or inhibitors of P450 3A (CYP3A) or CYP2C8 hepatic enzymes as listed in Section 6.5. of the protocol.
- The participant is receiving anticoagulant/antiplatelet therapies, including: Acetylsalicylic acid (aspirin) Antiplatelet drugs (eg, clopidogrel) E 09.
- The participant has sensitivity to any of the study interventions, or components thereof, or has a drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study.
- Prior/concurrent clinical study experience E 10.
- The participant was previously exposed to any BTK inhibitor, including SAR442168 E 11.
- The participant has taken other investigational drugs within 3 months or 5 half-lives, whichever is longer, before the screening visit.
- The participant has a contraindication for MRI, ie, presence of pacemaker, metallic implants in high risk areas (ie, artificial heart valves, aneurysm/vessel clips), presence of metallic material (eg, shrapnel) in high risk areas, known history of allergy to any contrast medium, or history of claustrophobia that would prevent completion of all protocol scheduled MRI Other exclusions E 13.
- Individuals accommodated in an institution because of regulatory or legal order; prisoners or participants who are legally institutionalized.
- Any country-related specific regulation that would prevent the participant from entering the study.
- See Appendix 9 (Section 10.9).
- Participants are dependent on the Sponsor or Investigator (in conjunction with Section 1.61 of the International Council for Harmonisation (ICH) Good Clinical Practice (GCP) Ordinance E6).
- Participants are employees of the clinical study site or other individuals directly involved in the conduct of the study, or immediate family members of such individuals.
- Any other situation during study implementation/course that may raise ethics considerations.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Time to onset of 6-month confirmed disability Progression (CDP) defined as follows: 24 weeks - Increase of ≥0.5 point when the baseline EDSS score is 5.5 24 weeks - Increase of ≥1.0 point from the baseline EDSS score when the baseline score is ≤5.0, OR 24 weeks
- Secondary Outcome Measures
Name Time Method Time to onset of 3-month CDP as assessed by the EDSS score Time to onset of sustained 20% increase in the 9-HPT confirmed over at least 3 months
Trial Locations
- Locations (8)
All India Institute of Medical Sciences
🇮🇳Delhi, DELHI, India
Artemis Hospital
🇮🇳Gurgaon, HARYANA, India
Fortis Hospital
🇮🇳Gurgaon, HARYANA, India
G B Pant Institute of Post-graduate Medical Education and Research
🇮🇳Delhi, DELHI, India
Justice K S Hegde Charitable Hospital
🇮🇳Kannada, KARNATAKA, India
Max Superspeciality Hospital
🇮🇳Delhi, DELHI, India
Sir Gangaram Hospital
🇮🇳Delhi, DELHI, India
Sparsh Super Specialty Hospital
🇮🇳Bangalore, KARNATAKA, India
All India Institute of Medical Sciences🇮🇳Delhi, DELHI, IndiaDr M V PadmaPrincipal investigator011126588500vasanthapadma123@gmail.com