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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Genzyme Corp.

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

4 Nov 2020 → 15 Nov 2025

Decision date (initial)

2024-07-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Sanofi-Aventis Recherche & Developpement

External identifiers

EU CT number

2024-514495-41-00

EudraCT number

2020-000645-14

WHO UTN

U1111-1238-1318

ClinicalTrials.gov

NCT04458051

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacodynamic, Pharmacogenomic, Therapy, Pharmacogenetic, Pharmacokinetic

To determine the efficacy of SAR442168 compared to placebo in delaying disability progression in Primary Progressive Multiple Sclerosis (PPMS)

Secondary objectives 4

1. To evaluate efficacy of SAR442168 compared to placebo on clinical endpoints, magnetic resonance imaging (MRI) lesions, cognitive performance, physical function, and quality of life
2. To evaluate safety and tolerability of SAR442168
3. To evaluate population pharmacokinetics (PK) of SAR442168 in PPMS and its relationship to efficacy and safety
4. To evaluate pharmacodynamics of SAR442168

Conditions and MedDRA coding

Primary Progressive Multiple Sclerosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 18 to 55 years of age inclusive
2. Diagnosis of PPMS according to the 2017 McDonald criteria
3. Expanded disability status scale (EDSS) score between 2.0 to 6.5 points, at screening inclusive
4. Positive cerebrospinal fluid oligoclonal bands and/or elevated Immunoglobulin G (IgG) index either during screening or documented previous history.
5. Contraceptive use consistent with local regulations for individuals participating in clinical studies
6. 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 - the participant must not have access to ocrelizumab (eg, ocrelizumab not available on the national market or not reimbursed for the approved indication). - the participant must have access to and be eligible to be treated with ocrelizumab but: 1) does not tolerate it due to side effects or safety reasons; and/or 2) has failed ocrelizumab treatment due to perceived lack of efficacy

Exclusion criteria 17

1. Participant has conditions that would adversely affect study participation such as short life expectancy.
2. Evidence of infection with human immunodeficiency virus (HIV), transplantation, progressive multifocal leukoencephalopathy (PML), active hepatitis B or C, active or latent tuberculosis or other active infection that would adversely affect study participation.
3. Persistent chronic or active or recurring system infection that may adversely affect participation or IMP administration in this study as judged by the investigator
4. History of malignancy within 5 years prior to screening.
5. History of alcohol or drug abuse within 1 year prior to Screening.
6. Hospitalized for psychiatric disease within 2 years prior to Screening.
7. Clinically significant laboratory abnormalities (including evidence of liver injury) or electrocardiogram abnormalities at Screening.
8. A bleeding disorder or known platelet dysfunction at any time prior to the screening visit.
9. A platelet count <150 000/μL at the screening visit.
10. 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
11. Lymphocyte count below the lower limit of normal at Screening.
12. Recent live (attenuated) vaccine within 2 months before the first treatment visit.
13. Recent major surgery (within 4 weeks of Screening) or planned major surgery during the study.
14. The participant has received medications/treatments for MS within a specified time frame.
15. Receiving potent and moderate inducers of cytochrome P450 3A (CYP3A) or potent inhibitors of CYP2C8 hepatic enzymes.
16. Receiving anticoagulant or antiplatelet therapy (such as aspirin >81mg/day, clopidogrel, warfarin).
17. Contraindications to magnetic resonance imaging (MRI).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 6-month composite Confirmed Disability Progression (cCDP)

Secondary endpoints 14

1. 6-month Confirmed Disability Progression (CDP)
2. 3-month composite Confirmed Disability Progression (cCDP)
3. Change in T2 hyperintense lesions by MRI
4. Time to onset of confirmed disability improvement (CDI)
5. Percent change in Brain volume (BV)
6. Change in cognitive function as assessed by SDMT
7. Change in cognitive function as assessed by CVLT-II
8. Change in Multiple Sclerosis Quality of Life
9. Safety and Tolerability
10. Population pharmacokinetics
11. Change in plasma neurofilament light chain (NfL)
12. Change in lymphocyte phenotype subsets
13. Changes in serum Immunoglobulin level
14. Change in serum chitinase-3 like protein 1 (Chi3L1)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Genzyme Corp.

Sponsor organisation

Genzyme Corp.

Address

450 Water Street

City

Cambridge

Postcode

02141-2288

Country

United States

Scientific contact point

Organisation

Genzyme Corp.

Contact name

Clinical Sciences and Operations

Public contact point

Organisation

Genzyme Corp.

Contact name

Clinical Sciences and Operations

Third parties 26

Locations

19 EU/EEA countries · 106 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 175 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications