Primary progressive multiple sclerosis (PPMS) Study of Bruton's tyrosine kinase (BTK) inhibitor SAR442168 (PERSEUS)

• Register: EUCTR
• Last refreshed on: 30 November 2020
• Main ID: EUCTR2020-000645-14-GB
• Date of registration: 07/10/2020
• Prospective Registration: Yes
• Primary sponsor: Genzyme Corporation
• Public title: Primary progressive multiple sclerosis (PPMS) Study of Bruton's tyrosine kinase (BTK) inhibitor SAR442168 (PERSEUS)
• Scientific title: A Phase 3, randomized, double-blind, efficacy and safety study comparing SAR442168 to placebo in participants with primary progressive multiple sclerosis (PERSEUS) - PERSEUS
• Date of first enrolment: 16/10/2020
• Target sample size: 1320
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-000645-14
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Belarus, Belgium, Bulgaria, Canada, Chile, China, Colombia, Croatia, Czechia, Denmark, Estonia, France, Germany, Greece, Hungary, India, Ireland, Israel, Italy, Japan, Latvia, Mexico, Netherlands, Norway, Peru, Poland, Portugal, Romania, Russian Federation, Serbia, Spain, Sweden, Switzerland, Turkey, Ukraine, United Kingdom, United States

Contacts

• Name: Medical Information
• Affiliation: Genzyme Europe B.V.

• Name: Medical Information
• Affiliation: Genzyme Europe B.V.

Key inclusion & exclusion criteria

Inclusion criteria:
- 18 to 55 years of age inclusive
- Diagnosis of PPMS according to the 2017 McDonald criteria
- Expanded disability status scale (EDSS) score between 2.0 to 6.5 points, at screening inclusive
- 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 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 child bearing potential (WOCBP)
OR
- Is a WOCBP and agrees to use an acceptable contraceptive method
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1320
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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 alchohol 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 or history of significant bleeding event within 6 months prior to 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).
NOTE: Other Inclusion/Exclusion criteria may apply


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Primary Progressive Multiple Sclerosis
MedDRA version: 21.1 Level: PT Classification code 10063401 Term: Primary progressive multiple sclerosis System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Product Code: SAR442168
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Not available
CAS Number: 1971920-73-6
Current Sponsor code: SAR442168
Other descriptive name: PRN2246
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 60-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

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

Timepoint(s) of evaluation of this end point: Up to approximately 48 months

Primary end point(s): 6 month Confirmed Disability Progression (CDP) ; 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 Objective: 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

Secondary Outcome(s)

Secondary end point(s): 1 - 3-month confirmed disability progression (CDP) ; Time to onset of 3-month CDP as assessed by EDSS score
2 - 3-month change in 9-hole peg test (9-HPT) ; 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 to onset of sustained 20% increase in the T25-FW confirmed over at least 3 months
4 - Change in T2 hyperintense lesions by MRI ; 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 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) ; Percent change in brain volume loss (BVL) as detected by brain MRI at the EOS compared to month 6
7 - Change in cognitive function ; Change in cognitive function at the EOS compared to baseline as assessed by the Symbol Digit Modalities Test (SDMT)
8 - Change in cognitive function ; Change in cognitive function at the EOS compared to baseline as assessed by the California Verbal Learning Test II (CVLT-II) where available
9 - Change in Multiple Sclerosis Quality of Life ; Change in Multiple Sclerosis Quality of Life-54 (MSQoL-54) at the EOS compared to baseline
10 - Safety and Tolerability ; 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 ; Plasma concentration of SAR442168 (population PK assessment) at Months 6, 9, and 12
12 - Change in plasma neurofilament light chain (NfL) ; Change in NfL levels from at the EOS compared to baseline
13 - Change in lymphocyte phenotype subsets ; Change in lymphocyte phenotype subsets in whole blood at the EOS compared to baseline
14 - Changes in serum Immunoglobulin level ; Changes in serum Immunoglobulin level at the EOS compared to baseline
15 - Change in serum chitinase-3 like protein 1 (Chi3L1) ; Change in serum chitinase-3 like protein 1 (Chi3L1) at EOS compared to baseline

Timepoint(s) of evaluation of this end point: 1, 2, 3 : Up to approximately 48 months
4 : From baseline to approximately 48 months
5 : From Baseline up to 48 approximately months
6 : From 6 months up to approximately 48 months
7, 8, 9, 12, 13, 14, 15 : From Baseline up to approximately 48 months
10 : From screening up to approximately 48 months
11 : Months 6, 9 and 12

Secondary ID(s)

EFC16035

2020-000645-14-FR

Source(s) of Monetary Support

Genzyme Corporation

Ethics review

Status: Approved
Approval date: 16/10/2020
Contact: