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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04411641




Registration number
NCT04411641
Ethics application status
Date submitted
28/05/2020
Date registered
2/06/2020
Date last updated
30/03/2021

Titles & IDs
Public title
Nonrelapsing Secondary Progressive Multiple Sclerosis (NRSPMS) Study of Bruton's Tyrosine Kinase (BTK) Inhibitor Tolebrutinib (SAR442168)
Scientific title
A Phase 3, Randomized, Double-blind, Efficacy and Safety Study Comparing SAR442168 to Placebo in Participants With Nonrelapsing Secondary Progressive Multiple Sclerosis
Secondary ID [1] 0 0
U1111-1246-7768
Secondary ID [2] 0 0
EFC16645
Universal Trial Number (UTN)
Trial acronym
HERCULES
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Secondary Progressive Multiple Sclerosis 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tolebrutinib
Treatment: Drugs - Placebo to match Tolebrutinib

Experimental: SAR442168 - Dose 1 of oral SAR442168 once daily

Placebo Comparator: Placebo - Placebo tablet to match SAR442168 once daily


Treatment: Drugs: Tolebrutinib
Pharmaceutical form: Film-coated tablet Route of administration: Oral

Treatment: Drugs: Placebo to match Tolebrutinib
Pharmaceutical form: Film-coated tablet Route of administration: Oral

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
6-month confirmed disability progression (CDP) - Time to onset of 6 months CDP defined as follows:
-Increase of =1.0 point from the baseline expanded disability status scale (EDSS) score when the baseline score is =5.0, or -Increase of =0.5 point when the baseline EDSS score is >5.0 -
Timepoint [1] 0 0
Up to 48 approximately months
Secondary outcome [1] 0 0
3-months change in T25-FW and 9-HPT - Time to onset of composite CDP, confirmed over at least 3 months (3-month CCDP), by the EDSS Plus composite (EDSS score increase, or 20% increase in the T25 FW test, or 20% increase in the 9 hole peg test (9 HPT)
Timepoint [1] 0 0
Up to approximately 48 months
Secondary outcome [2] 0 0
3-month CDP - Time to onset of 3-month CDP as assessed by EDSS score
Timepoint [2] 0 0
Up to approximately48 months
Secondary outcome [3] 0 0
New and enlarging T2 hyperintense lesions by MRI - Total number of new or enlarging T2 hyperintense lesions as detected by MRI
Timepoint [3] 0 0
From Baseline up to approximately 48 months
Secondary outcome [4] 0 0
Time to onset of confirmed disability improvement (CDI) - Time to CDI defined as =1.0 point decrease on the EDSS score from baseline confirmed over at least 6 months
Timepoint [4] 0 0
From Baseline up to approximately 48 months
Secondary outcome [5] 0 0
Brain volume loss (BVL) - Percent change in Brain volume loss (BVL) as detected by brain MRI at the EOS compared to month 6
Timepoint [5] 0 0
From 6 Months up to approximately 48 months
Secondary outcome [6] 0 0
Change in cognitive function - Change in cognitive function at the EOS compared to baseline as assessed by the Symbol Digit Modalities Test (SDMT) and by the California Verbal Learning Test (CVLT-II) -
Timepoint [6] 0 0
From Baseline up to approximately 48 months
Secondary outcome [7] 0 0
Change in Multiple Sclerosis Quality of Life-54 (MSQoL-54) - Change in Multiple Sclerosis Quality of Life-54 (MSQoL-54) from the baseline through the EOS
Timepoint [7] 0 0
From Baseline up to approximately 48 months
Secondary outcome [8] 0 0
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)
Timepoint [8] 0 0
From Screening until end of study up to approximately 48 months
Secondary outcome [9] 0 0
Population pharmacokinetics - Plasma concentration of SAR442168 and relevant metabolites (population PK assessment) at Months 6, 9, and 12
Timepoint [9] 0 0
Months 6, 9 and 12
Secondary outcome [10] 0 0
Change in plasma neurofilament light chain (NfL) - Change in NfL levels at the EOS compared to baseline -
Timepoint [10] 0 0
From Baseline up to approximately 48 months
Secondary outcome [11] 0 0
Changes in serum Immunoglobulin level - Changes in serum Immunoglobulin level at the EOS compared to baseline
Timepoint [11] 0 0
From Baseline up to approximately 48 months
Secondary outcome [12] 0 0
Change in lymphocyte phenotype subsets - Change in lymphocyte phenotype subsets in whole blood at the EOS compared to baseline
Timepoint [12] 0 0
From Baseline up to approximately 48 months
Secondary outcome [13] 0 0
Change in serum chitinase-3 like protein 1 (Chi3L1) - Change in serum chitinase-3 like protein 1 (Chi3L1) at the EOS compared to baseline
Timepoint [13] 0 0
From Baseline up to approximately 48 months

Eligibility
Key inclusion criteria
Inclusion criteria :

- 18 to 60 years of age inclusive

- Diagnosis of nonrelapsing secondary progressive multiple sclerosis according to the
2017 McDonald criteria

- Expanded disability status scale (EDSS) between 3.0 to 6.5 points inclusive, at
screening

- The participant must have documented evidence of disability progression observed
during the 12 months before screening

- Absence of clinical relapses for at least 24 months

- Contraceptive use by men or women should be consistent with local regulations
regarding the methods of contraception for those participating in clinical studies

- 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 WOCBP OR

- Is a WOCBP and agrees to use an acceptable contraceptive method
Minimum age
18 Years
Maximum age
60 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

- The participant has conditions that would adversely affect study participation such as
short life expectancy.

- History of organ transplant.

- Evidence of infection with human immuodeficiency virus (HIV), progressive multifocal
leukoencephalopathy (PML), active hepatitis B or C, active or latent tuberculosis or
other active infections that would adversely affect study participation.

- History of malignancy within 5 years prior to screening.

- History of alcohol 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.

- 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 bleeding.

- 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).

The above information is not intended to contain all considerations relevant to a patient's
potential participation in a clinical trial.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Investigational Site Number 0360001 - Fitzroy
Recruitment hospital [2] 0 0
Investigational Site Number 0360006 - Heidelberg West
Recruitment hospital [3] 0 0
Investigational Site Number 0360004 - Hobart
Recruitment hospital [4] 0 0
Investigational Site Number 0360002 - Kent Town
Recruitment hospital [5] 0 0
Investigational Site Number 0360003 - Woolloongabba
Recruitment postcode(s) [1] 0 0
3065 - Fitzroy
Recruitment postcode(s) [2] 0 0
3081 - Heidelberg West
Recruitment postcode(s) [3] 0 0
7001 - Hobart
Recruitment postcode(s) [4] 0 0
- Kent Town
Recruitment postcode(s) [5] 0 0
4102 - Woolloongabba
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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California
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Michigan
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Madrid
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Murcia
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Málaga
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Pozuelo De Alarcón
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Salt
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Sevilla
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Spain
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Valencia
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Turkey
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Eskisehir
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Turkey
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Istanbul
Country [118] 0 0
Turkey
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Izmit
Country [119] 0 0
Ukraine
State/province [119] 0 0
Chernivtsi
Country [120] 0 0
Ukraine
State/province [120] 0 0
Dnipro
Country [121] 0 0
Ukraine
State/province [121] 0 0
Ivano-Frankivsk
Country [122] 0 0
Ukraine
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Kharkiv
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Ukraine
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Kyiv
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Lutsk
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Ukraine
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Lviv
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Ukraine
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Odesa
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Vinnitsa
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Ukraine
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Zhytormyr

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Sanofi
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Primary Objective:

To determine the efficacy of SAR442168 compared to placebo in delaying disability progression
in NRSPMS

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 and relevant metabolites in NRSPMS and its relationship to efficacy and
safety To evaluate pharmacodynamics (PD) of SAR442168
Trial website
https://clinicaltrials.gov/show/NCT04411641
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Sciences & Operations
Address 0 0
Sanofi
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Trial Transparency email recommended (Toll free number for US & Canada)
Address 0 0
Country 0 0
Phone 0 0
800-633-1610
Fax 0 0
Email 0 0
Contact-US@sanofi.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04411641