Clinical trial NCT04879628: Proof-of-concept Study for SAR441344 (Frexalimab) in Relapsing Multiple Sclerosis
Official title: A Phase 2, Double-blind, Randomized, Placebo-controlled Study Assessing Efficacy and Safety of SAR441344, a CD40L-antagonist Monoclonal Antibody, in Participants With Relapsing Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Multiple Sclerosis
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2021-05-10
Enrollment: 129
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Part A is a 12-week, double-blind, placebo-controlled part; Part B is an open-label SAR441344 treatment part.
Primary purpose: TREATMENT

Brief summary: Primary Objective:

To determine the efficacy of SAR441344 as measured by reduction of the number of new active brain lesions

Secondary Objective:

* To evaluate efficacy of SAR441344 on disease activity as assessed by other MRI measures
* To evaluate the safety and tolerability of SAR441344
* To evaluate pharmacokinetics of SAR441344

Detailed description: The duration of each participant will be no longer than 320weeks in both parts of the study, including 4 weeks of screening, at maximum 292 weeks of treatment and 24 weeks of follow-up.

Eligibility criteria: Inclusion criteria:

* Participant must be 18 to 55 years of age inclusive, at the time of signing the informed consent.
* The participant must have been diagnosed with RMS (relapsing-remitting MS and secondary progressive MS participants with relapses) according to the 2017 revision of the McDonald diagnostic criteria.
* The participant must have at least 1 documented relapse within the previous year, or ≥2 documented relapses within the previous 2 years, or ≥1 active Gd-enhancing brain lesion on an MRI scan in the past 6 months and prior to screening.
* Body weight within 45 to 120 kg (inclusive) and body mass index (BMI) within the range 18.0 to 35.0 kg/m2 (inclusive) at Screening.
* Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
* Capable of giving signed informed consent.

Exclusion criteria:

* The participant has been diagnosed with PPMS according to the 2017 revision of the McDonald diagnostic criteria or with non-relapsing SPMS.
* The participant has conditions or situations that would adversely affect participation in this study.
* The participant has a history of or currently has concomitant medical or clinical conditions that would adversely affect participation in this study.
* History, clinical evidence, suspicion or significant risk for thromboembolic events, as well as myocardial infarction, stroke and/or antiphosholipid syndrome and any participants requiring antithrombotic treatment.
* Allergies to humanized monoclonal antibodies or severe post-treatment hypersensitivity reactions other than localized injection site reaction, to any biological molecule.
* The participant has received any of the forbidden medications/treatments within the specified time frame before any baseline assessment.
* The participant has taken other investigational drug within 3 months or 5-half-live, whichever is longer, before the screening visit.
* The participant has an EDSS score \>5.5 at the first screening visit.
* The participant has had a relapse in the 30 days prior to randomization.
* Positive human immunodeficiency virus (HIV) serology (anti HIV1 and anti HIV2 antibodies) or a known history of HIV infection, active or in remission.
* Abnormal laboratory test(s) at Screening.
* Presence of Hepatitis B surface antigen (HBsAg) or anti-Hepatitis B core antibodies (anti-HBc Ab) at screening or within 3 months prior to first dose of study intervention.
* Positive Hepatitis C antibody test result at screening or within 3 months prior to starting study intervention.

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

Primary outcomes:
measure: Number of new Gadolinium (Gd)-enhancing T1-hyperintense (GdE T1) lesions
timeFrame: At Week 12
Secondary outcomes:
measure: Number of new or enlarging T2 lesions
timeFrame: At Week 12
measure: Total number of GdE T1 lesions
timeFrame: At Week 12
measure: Adverse events (AEs) and serious adverse events (SAEs)
timeFrame: Until Week 316
measure: Antidrug antibodies (ADA)
timeFrame: Until Week 316
measure: Pharmacokinetic (PK) parameters: Cmax
timeFrame: Until Week 316
measure: PK parameter: tmax
timeFrame: Until Week 316
measure: PK parameter: AUC0-tau
timeFrame: Until Week 316
measure: PK parameter: t1/2z
timeFrame: Until Week 316
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Center for Neurology and Spine Site Number : 8400007
state: Arizona
city: Tampa
country: United States
facility: University of South Florida Site Number : 8400001
state: Florida
city: Charlotte
country: United States
facility: The Neurological Institute Site Number : 8400004
state: North Carolina
city: Milwaukee
country: United States
facility: Medical College of Wisconsin Site Number : 8400006
state: Wisconsin
city: Pleven
country: Bulgaria
facility: Investigational Site Number : 1000002
city: Sofia
country: Bulgaria
facility: Investigational Site Number : 1000003
city: Sofia
country: Bulgaria
facility: Investigational Site Number : 1000001
city: Gatineau
country: Canada
facility: Investigational Site Number : 1240001
state: Quebec
city: Brno
country: Czechia
facility: Investigational Site Number : 2030003
city: Hradec Kralove
country: Czechia
facility: Investigational Site Number : 2030002
city: Jihlava
country: Czechia
facility: Investigational Site Number : 2030001
city: Ostrava - Poruba
country: Czechia
facility: Investigational Site Number : 2030005
city: Teplice
country: Czechia
facility: Investigational Site Number : 2030004
city: Calais
country: France
facility: Investigational Site Number : 2500006
city: Gießen
country: Germany
facility: Investigational Site Number : 2760001
city: Leipzig
country: Germany
facility: Investigational Site Number : 2760012
city: Münster
country: Germany
facility: Investigational Site Number : 2760004
city: Kazan
country: Russian Federation
facility: Investigational Site Number : 6430002
city: Moscow
country: Russian Federation
facility: Investigational Site Number : 6430007
city: Moscow
country: Russian Federation
facility: Investigational Site Number : 6430006
city: Moscow
country: Russian Federation
facility: Investigational Site Number : 6430001
city: Saint-Petersburg
country: Russian Federation
facility: Investigational Site Number : 6430004
city: St-Petersburg
country: Russian Federation
facility: Investigational Site Number : 6430003
city: St-Petersburg
country: Russian Federation
facility: Investigational Site Number : 6430005
city: Tyumen
country: Russian Federation
facility: Investigational Site Number : 6430008
city: Barcelona
country: Spain
facility: Investigational Site Number : 7240004
state: Barcelona [Barcelona]
city: Vigo
country: Spain
facility: Investigational Site Number : 7240002
city: Eskisehir
country: Turkey
facility: Investigational Site Number : 7920004
city: Istanbul
country: Turkey
facility: Investigational Site Number : 7920003
city: Izmit
country: Turkey
facility: Investigational Site Number : 7920001
city: Mersin
country: Turkey
facility: Investigational Site Number : 7920002
city: Dnipro
country: Ukraine
facility: Investigational Site Number : 8040010
city: Dnipro
country: Ukraine
facility: Investigational Site Number : 8040006
city: Ivano-Frankivsk
country: Ukraine
facility: Investigational Site Number : 8040008
city: Kyiv
country: Ukraine
facility: Investigational Site Number : 8040002
city: Lviv
country: Ukraine
facility: Investigational Site Number : 8040004
city: Odesa
country: Ukraine
facility: Investigational Site Number : 8040003
city: Vinnytsia
country: Ukraine
facility: Investigational Site Number : 8040005
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: