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CTRI Number  CTRI/2020/10/028392 [Registered on: 13/10/2020] Trial Registered Prospectively
Last Modified On: 19/04/2022
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group, Placebo Controlled Trial 
Public Title of Study   Primary progressive multiple sclerosis (PPMS) study of BTK inhibitor SAR442168 (PERSEUS) 
Scientific Title of Study   A Phase 3, randomized, double-blind, efficacy and safety study comparing SAR442168 to placebo in participants with primary progressive multiple sclerosis 
Trial Acronym  PERSEUS 
Secondary IDs if Any  
Secondary ID  Identifier 
EFC16035 Version No.01 Amendment No. 01 dated 25 Jun 2020  Protocol Number 
2020-000645-14  EudraCT 
U1111-1238-1318  Other 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name   
Designation   
Affiliation   
Address 




 
Phone    
Fax    
Email    
 
Details of Contact Person
Scientific Query

Modification(s)  
Name  Dr Saket Thaker 
Designation  Senior Medical Advisor and Clinical Safety Lead 
Affiliation  Sanofi Healthcare India Private Limited 
Address  Sanofi House, CTS No.117-B, L&T Business Park Saki Vihar Road, Powai

Mumbai
MAHARASHTRA
400072
India 
Phone    
Fax    
Email  Saket.Thaker@sanofi.com  
 
Details of Contact Person
Public Query

Modification(s)  
Name  Dr Vishal Patil 
Designation  Clinical Project Leader 
Affiliation  Sanofi Healthcare India Private Limited 
Address  Sanofi House, CTS No.117-B, L&T Business Park Saki Vihar Road, Powai

Mumbai
MAHARASHTRA
400072
India 
Phone  9823088050  
Fax    
Email  Vishal.Patil@Sanofi.com  
 
Source of Monetary or Material Support
Modification(s)  
Sanofi Healthcare India Private Limited Sanofi House, CTS No.117-B, L&T Business Park Saki Vihar Road, Powai Mumbai:400072 
 
Primary Sponsor
Modification(s)  
Name  Sanofi Healthcare India Private Limited 
Address  Sanofi Healthcare India Private Limited, Sanofi House, CTS No. 117-B, L&T Business Park, Powai, Mumbai – 400072 
Type of Sponsor  Pharmaceutical industry-Global 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     Belgium
Canada
Denmark
France
Germany
Greece
Hungary
India
Italy
Japan
Netherlands
Norway
Poland
Portugal
Russian Federation
Spain
Sweden
United Kingdom
United States of America  
Sites of Study
Modification(s)  
No of Sites = 8  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr M V Padma  All India Institute of Medical Sciences  Dept. of Neurology, Neuroscience Centre, Ansari Nagar, Ansari Nagar East
New Delhi
DELHI 
011126588500

vasanthapadma123@gmail.com 
Dr Manish Mahajan  Artemis Hospital  Sector 51, Gurugram
Gurgaon
HARYANA 
8557873567

drmanishneurology@gmail.com 
Dr Praveen Gupta  Fortis Hospital   Fortis Memorial Fortis Memorial Research Institute Sector 44, Opp Huda City Centre, Gurugram
Gurgaon
HARYANA 
9891907903

praveen.gupta@fortishealthcare.com 
Dr Debashish Chaudhury  G B Pant Institute of Post-graduate Medical Education and Research  1, Jawaharlal Nehru Marg, 64 Khamba, Raj Ghat, New Delhi, Delhi 110002
New Delhi
DELHI 
919718599306

profdebashishchowdhury@gmail.com 
Dr Lekha Pandit  Justice K S Hegde Charitable Hospital  Medical Sciences Complex, Deralakatte, Mangalore
Dakshina Kannada
KARNATAKA 
08242202392

panditmng@gmail.com 
Dr JoyDev Mukherji  Max Superspeciality Hospital   Saket (west block), 1 Press enclave Road, New Delhi-110017, India
New Delhi
DELHI 
919958989138

jd.mukherji@maxhealthcare.com 
Dr Netravathi M  National Institute of Mental health and Neurosciences  Hosur Rd, near Bangalore Milk Dairy, Lakkasandra, Laljinagar, Wilson Garden
Bangalore
KARNATAKA 
9880106662

sundernetra@yahoo.co.in 
Dr Anshu Rohatgi  Sir Gangaram Hospital  Old Rajinder Nagar , New Delhi- 110060
New Delhi
DELHI 
01142251412

rohatagianshu@yahoo.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 8  
Name of Committee  Approval Status 
Artemis health Sciences Institutional Ethics Committee_Dr Manish Mahajan  Approved 
Central Ethics Committee_Dr Lekha Pandit  Approved 
IEC_Dr Praveen Gupta  Approved 
Institutional Ethics Committee MAMC and associated hospitals, New Delhi  Approved 
Instutional Ethics Comittee_Dr M V Padma  Approved 
Max Healthcare Ethics committee, New Delhi  Approved 
NIMHANS Ethics Committee_Dr. Netravathi M  Submittted/Under Review 
Sir Ganga Ram Hospital Ethics Committee_Dr Anshu Rohtagi  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: G35||Multiple sclerosis,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  Arm name: Placebo  Unit dose strength(s) 0 mg Dose formulation Tablet Dosage level(s) Once daily Route of administration Oral  
Intervention  Arm name: SAR442168 Intervention name: SAR442168 60 mg or Placebo matched to SAR442168   Dose formulation Tablet Unit dose strength(s) 60 mg Dosage level(s) Once daily Route of administration Oral  
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  55.00 Year(s)
Gender  Both 
Details  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). 
 
ExclusionCriteria 
Details  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.
E 05. Conditions that would adversely affect participation in the study or make the primary efficacy endpoint non-evaluable:
A short life expectancy due to pre-existing health condition(s) as determined by their treating neurologist.
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.
E 08. 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.
E 12. 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.
E 14. Any country-related specific regulation that would prevent the participant from entering the study. See Appendix 9 (Section 10.9).
E 15. 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).
E 16. 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.
E 17. Any other situation during study implementation/course that may raise ethics considerations.

 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Centralized 
Blinding/Masking   Participant and Investigator Blinded 
Primary Outcome  
Outcome  TimePoints 
Time to onset of 6-month confirmed disability Progression (CDP) defined as follows:
- Increase of ≥1.0 point from the baseline EDSS score when the baseline score is ≤5.0, OR
- Increase of ≥0.5 point when the baseline EDSS score is 5.5
 
24 weeks 
 
Secondary Outcome  
Outcome  TimePoints 
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
Time to onset of sustained 20% increase in the T25-FW test confirmed over at least 3 months
Total number of new and/or enlarging T2-hyperintense lesions as detected by MRI,
defined as the sum of the individual number of new and/or enlarging T2 lesions at all scheduled visits starting after baseline up to and including the EOS visit
 
24 weeks 
 
Target Sample Size   Total Sample Size="900"
Sample Size from India="40" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   Phase 3 
Date of First Enrollment (India)   30/12/2020 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  19/10/2020 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="3"
Months="8"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  
Open to Recruitment 
Recruitment Status of Trial (India)  Open to Recruitment 
Publication Details   NIL 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - NO
Brief Summary   SAR442168 is expected to reduce MS relapse rate, disability progression, and underlying central nervous system (CNS) damage through its dual action on adaptive immunity in the periphery and innate immunity and the inflammation process in the CNS. The results from the Phase 2b trial (DRI15928) demonstrated a doseresponse relationship for SAR442168 as evidenced by a reduction in the number of new Gd-enhancing T1-hyperintense brain lesions detected by brain MRI after 12 weeks of treatment. There was an 85% relative reduction in lesions at 12 weeks in the 60 mg dose group as compared with placebo. This was obtained from the negative binomial regression model adjusted for baseline Gd-enhancing T1-hyperintense lesion activity.
PPMS accounts for approximately 10 to 15 percent all patients with MS. In general, chronic disability accumulation remains a significant unmet need for people living with MS. Individuals with progressive MS need therapies to reduce the accumulation of disability. There is no approved treatment for PPMS in India. Evidence of inflammation and presence of activated T and B cells in the brain have been confirmed in PPMS, especially in the early stages.4 However, immunomodulatory therapies have shown very little effect on disease activity in these patients. Even the most recent high-efficacy immunomodulatory agents act mainly on adaptive immunity in the periphery with only modest or temporary ability to slow neuroinflammatory and neurodegenerative processes and stop disease progression. 5,6 As mentioned above, this may relate to conditions in the CNS, especially the integrity of the blood-brain barrier, but also to the potency and mechanism of action of the agents.
Thus, there is still a significant unmet need for therapies with new modes of action that target neuroinflammation in the CNS with a goal of halting long-term disability and neurodegeneration in all categories of MS including PPMS 
 
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