Clinical Trials Register

Summary
EudraCT Number:	2020-000645-14
Sponsor's Protocol Code Number:	EFC16035
National Competent Authority:	Estonia - SAM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2020-08-24
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Estonia - SAM

A.2

EudraCT number

2020-000645-14

A.3

Full title of the trial

A Phase 3, randomized, double-blind, efficacy and safety study comparing SAR442168 to placebo in participants with primary progressive multiple sclerosis (PERSEUS)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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

A.3.2

Name or abbreviated title of the trial where available

PERSEUS

A.4.1

Sponsor's protocol code number

EFC16035

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1238-1318

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Genzyme Corporation
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Genzyme Corporation
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Sanofi AB
B.5.2	Functional name of contact point	Clinical Study Unit
B.5.3	Address:
B.5.3.1	Street Address	Box 30052
B.5.3.2	Town/ city	Stockholm
B.5.3.3	Post code	10425
B.5.3.4	Country	Sweden
B.5.4	Telephone number	+46 86345000
B.5.6	E-mail	clinicaltrials.sweden@sanofi.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.2	Product code	SAR442168
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not available
D.3.9.1	CAS number	1971920-73-6
D.3.9.2	Current sponsor code	SAR442168
D.3.9.3	Other descriptive name	PRN2246
D.3.9.4	EV Substance Code	SUB195428
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	60
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Primary Progressive Multiple Sclerosis

E.1.1.1

Medical condition in easily understood language

Primary Progressive Multiple Sclerosis

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10063401
E.1.2	Term	Primary progressive multiple sclerosis
E.1.2	System Organ Class	10029205 - Nervous system disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

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

E.2.2

Secondary objectives of the trial

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

E.2.3

Trial contains a sub-study

E.3

Principal 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

E.4

Principal 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), transplantation, progressive multifocal leukoencephalopathy (PML), active hepatitis B or C, active or latent tuberculosis or other active infection that would adversely affect study participation.
-Persistent chronic or active or recurring system infection that may adversely affect participation or IMP administration in this study as judged by the investigator
- 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.
- 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.
- 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
- 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 potent and moderate inducers of cytochrome P450 3A (CYP3A) or potent inhibitors of CYP2C8 hepatic enzymes.
- Receiving anticoagulant or antiplatelet therapy (such as aspirin >81mg/day, clopidogrel, warfarin).
- Contraindications to magnetic resonance imaging (MRI).
NOTE: Other Inclusion/Exclusion criteria may apply

E.5 End points

E.5.1

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

E.5.1.1

Timepoint(s) of evaluation of this end point

Up to approximately 48 months

E.5.2

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 in a subset of participants
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

E.5.2.1

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

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

140

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Argentina

Australia

Brazil

Canada

Chile

China

Colombia

Egypt

India

Israel

Japan

Kuwait

Mexico

Peru

Saudi Arabia

South Africa

United Arab Emirates

United States

Austria

Estonia

France

Latvia

Poland

Sweden

Bulgaria

Netherlands

Romania

Spain

Switzerland

Czechia

Germany

Greece

Italy

Belarus

Belgium

Croatia

Denmark

Georgia

Hungary

Ireland

Norway

Portugal

Russian Federation

Turkey

Ukraine

United Kingdom

Serbia

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

This study will end when approximately 290 primary endpoint events of 6-month CDP have been observed.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

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)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

599

F.4.2.2

In the whole clinical trial

1320

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Participants completing the treatment period will be proposed to enroll in a separate long term safety study

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2020-11-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-09-04

P. End of Trial
P.	End of Trial Status	Ongoing

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials