| CTRI Number |
CTRI/2020/10/028392 [Registered on: 13/10/2020] Trial Registered Prospectively |
| Last Modified On: |
08/05/2023 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
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Type of Study
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Drug |
| Study Design |
Randomized, Parallel Group, Placebo Controlled Trial |
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Public Title of Study
|
Primary progressive multiple sclerosis (PPMS) study of BTK inhibitor SAR442168 (PERSEUS) |
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Scientific Title of Study
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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 |
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Details of Principal Investigator or overall Trial Coordinator (multi-center study)
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| Name |
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| Designation |
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| Affiliation |
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| Address |
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| Phone |
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| Fax |
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| Email |
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Details of Contact Person
Scientific Query
Modification(s)
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| Name |
Dr Godhuli Chatterjee |
| Designation |
Senior Medical Advisor |
| 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 |
919930151289 |
| Fax |
|
| Email |
Godhuli.Chatterjee@sanofi.com |
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Details of Contact Person
Public Query
Modification(s)
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| Name |
Nishant Kharb |
| 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 |
8860222559 |
| Fax |
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| Email |
nishant.kharb@sanofi.com |
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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 |
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Primary Sponsor
Modification(s)
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| 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 |
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Details of Secondary Sponsor
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Countries of Recruitment
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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)
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| 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 Anshu Rohatgi |
Sir Gangaram Hospital |
Old Rajinder Nagar , New Delhi- 110060
New Delhi
DELHI |
01142251412
rohatagianshu@yahoo.com |
| Dr Rajesh B Iyer |
Sparsh Super Specialty Hospital |
146 Infantry road Opposite to police commissioners office Bangalore 560001
Bangalore
KARNATAKA |
9606197707
sparshclinical@gmail.com |
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Details of Ethics Committee
Modification(s)
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| 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, Sparsh Hospital_Dr Rajesh B Iyer |
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 |
| Sir Ganga Ram Hospital Ethics Committee_Dr Anshu Rohtagi |
Approved |
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Regulatory Clearance Status from DCGI
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Health Condition / Problems Studied
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| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: G35||Multiple sclerosis, |
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Intervention / Comparator Agent
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| 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
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Inclusion Criteria
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| 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.
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Method of Generating Random Sequence
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Computer generated randomization |
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Method of Concealment
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Centralized |
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Blinding/Masking
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Participant and Investigator Blinded |
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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
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24 weeks |
|
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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
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24 weeks |
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Target Sample Size
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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" |
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Phase of Trial
|
Phase 3 |
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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 |
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Estimated Duration of Trial
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Years="3"
Months="8"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Open to Recruitment |
| Recruitment Status of Trial (India) |
Open to Recruitment |
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Publication Details
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NIL |
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Individual Participant Data (IPD) Sharing Statement
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Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
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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 dose–response 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 |