Clinical trial NCT05630547: A Study to Evaluate the Effect of SAR443820 on Serum Neurofilament Levels in Male and Female Adult Participants With Multiple Sclerosis
Official title: A Phase 2 Double-blind, Randomized, Placebo-controlled Study Evaluating the Effect of SAR443820 on Serum Neurofilament Levels in Participants With Multiple Sclerosis, Followed by an Open-label Long-term Extension Period
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Multiple Sclerosis
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2022-11-29
Enrollment: 174
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase 2, randomized, double-blind, placebo-controlled 2 parallel-arm study to assess the effect on serum neurofilament light chain (sNfL), safety and tolerability of oral SAR443820 compared to placebo in male and female participants aged 18 to 60 years with relapsing-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS) (relapsing or non-relapsing), or primary progressive multiple sclerosis (PPMS) followed by an open-label long-term extension period.

The total study duration is approximately 100 weeks and includes the following:

4-week screening period 48-week double-blind treatment period (Part A) 48-week open-label long-term extension period (Part B)

Detailed description: Approximately 100 weeks

Eligibility criteria: Inclusion Criteria:

* Male or female, 18 to 60 years (inclusive) of age, at the time of signing the informed consent.
* Participants with diagnosis of RRMS, SPMS (relapsing or non-relapsing) or primary progressive subtype according to the 2017 revision of the McDonald diagnostic criteria (SPMS diagnostic criteria according to initial relapsing remitting disease course followed by progression with or without occasional relapses, minor remissions, and plateaus; progression denotes the continuous worsening of neurological impairment over at least 6 months).
* Participants with Expanded Disability Status Scale (EDSS) score of 26 inclusive at screening.
* Participants who are either untreated or in the opinion of the Investigator are stable on an allowed disease-modifying therapy (DMT) (interferons, glatiramer acetate, fumarates, or teriflunomide) for at least the past 3 months, AND not anticipated to require a change in multiple sclerosis (MS) treatment for the duration of Part A and Part B (through Week 96); in Part B changes in dose of allowed DMTs or transition to other allowed DMTs is permitted).
* Participants with body weight at least 45 kg and body mass index (BMI) at least 18.0 kg/m\^2.
* Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Exclusion Criteria:

* Participants with immunodeficiency syndromes or other autoimmune diseases requiring immunosuppressive therapy
* Participants with a history of seizures or epilepsy (history of febrile seizure during childhood is allowed).
* Participants with known clinical relapse (acute or subacute episodes of new or increasing neurological dysfunction followed by full or partial recovery, in absence of fever or infection) within 8 weeks of screening.
* Participants with neurological disease history other than MS, eg, head trauma within 3 months, cerebrovascular disease, and vascular dementia.
* Participants with a history of recent serious infection (eg, pneumonia, septicemia) within 4 weeks of screening; an infection requiring hospitalization or intravenous antibiotics, antivirals, or antifungals within 4 weeks of screening; or chronic bacterial infections (such as tuberculosis) deemed unacceptable, as per Investigator's judgment.
* Participants who have significant cognitive impairment, psychiatric disease, other neurodegenerative disorders (eg, Parkinson disease or Alzheimer disease), substance abuse, or any other conditions that would make the participants unsuitable for participating in the study or could interfere with assessment or completing the study in the opinion of the Investigator.
* Participants with a documented history of attempted suicide over the 24 weeks prior to the Screening Visit, presents with suicidal ideation of category 4 or 5 on the Columbia Suicide Severity Rating Scale (CSSRS), or if in the Investigator's judgment, the participant is at risk for a suicide attempt.
* Participants with a history of unstable or severe cardiac, pulmonary, oncological, hepatic, or renal disease or another medically significant illness other than MS precluding their safe participation in this study.
* Participants who received a live vaccine within 14 days before the Screening Visit.
* Participants with a known history of allergy to any ingredients of SAR443820 (mannitol, lactose monohydrate, sodium starch glycolate, colloidal silicon dioxide, magnesium stearate, hypromellose, titanium dioxide, polyethylene glycol, and microcrystalline cellulose). - Participants with a current use of any medications that are moderate or strong inhibitors or strong inducers of cytochrome P450 3A4 (CYP3A4).
* Participants with a current use of any of the following medications/treatments: fampridine/dalfampridine, ofatumumab, fingolimod, cladribine, siponimod, ponesimod, ozanimod, alemtuzumab, mitoxantrone, ocrelizumab, natalizumab, or similar approved compounds but with different trade names and any unapproved treatments or therapies for MS; any DMTs newly approved after January 2023 that are marketed at any time during the course of the double-blind study period. These medications are not allowed within 5 half-lives before the Screening Visit and for the duration of Part A and Part B.
* Participants who have prior/concurrent clinical study enrollment, ie, the participant has taken other investigational drugs within 4 weeks or 5 half-lives, whichever is longer, before the first Screening Visit; concurrent or recent participation in non-interventional studies may be permitted.

Participants with abnormal laboratory test(s) at the Screening Visit:

* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) more than 3.0 x upper limit of normal (ULN)
* Bilirubin more than 1.5 x ULN; unless the participant has documented Gilbert syndrome (isolated bilirubin more than 1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35%)
* Serum albumin less than 3.5 g/dL
* Estimated Glomerular filtration rate less than 60 mL/min/1.73 m\^2 (Modification of Diet in Renal Disease \[MDRD\])
* Other abnormal laboratory values or electrocardiogram (ECG) changes that are deemed clinically significant as per Investigator's judgment
* The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial

Primary outcomes:
measure: Part A: Week 48 sNfL levels relative to baseline
timeFrame: From baseline (Week 0) to Week 48
measure: Part B: Week 96 sNfL levels relative to baseline
timeFrame: From baseline (Week 0) to Week 96
Secondary outcomes:
measure: Part A: Cumulative number of new gadolinium (Gd)-enhancing T1 hyperintense lesions as detected by magnetic resonance imaging (MRI)
timeFrame: Baseline (Week 0) to Week 48
measure: Part A: Cumulative number of new and/or enlarging T2 hyperintense lesions as detected by MRI
timeFrame: Baseline (Week 0) to Week 48
measure: Part A: Time to onset of 12 weeks confirmed disability progression (CDP) from baseline as assessed by the Expanded Disability Status Scale (EDSS) score
timeFrame: Up to Week 48
measure: Part A: Time to onset of sustained 20% increase in 9-Hole Peg Test (9-HPT) confirmed over at least 12 weeks
timeFrame: Up to Week 48
measure: Part A: Time to onset of sustained 20% increase in timed 25-foot walk test (T25-FW) confirmed over at least 12 weeks
timeFrame: Up to Week 48
measure: Part A: Change from baseline in EDSS Plus
timeFrame: From baseline (Week 0) to Week 48
measure: Part A: Annualized relapse rate (ARR) of RMS population (relapsing SPMS and RRMS)
timeFrame: Up to Week 48
measure: Part A: Percent change from baseline in brain volume loss (BVL) as detected by brain MRI
timeFrame: From baseline (Week 0) to Weeks 48
measure: Part A: Change from baseline in the volume of slowly expanding lesions (SELs)
timeFrame: From baseline (Week 0) to Weeks 12, 24, 36 and 48
measure: Part A: Change from baseline in the number of SELs
timeFrame: From baseline (Week 0) to Weeks 12, 24, 36 and 48
measure: Part A: Change from baseline in the intensity (T1) of SELs
timeFrame: From baseline (Week 0) to Weeks 12, 24, 36 and 48
measure: Part A: Change from baseline in the normalized T1 intensity in lesions
timeFrame: From baseline (Week 0) to Weeks 12, 24, 36 and 48
measure: Part A: Change from baseline in the total number of non-enhancing lesions
timeFrame: From baseline (Week 0) to Weeks 12, 24, 36 and 48
measure: Part A: Change from baseline in the volume of non-enhancing lesions
timeFrame: From baseline (Week 0) to Weeks 12, 24, 36 and 48
measure: Part A: Change from baseline in the number of phase rim lesions (PRL) will be conducted at 3 Tesla (3T) capable sites
timeFrame: From baseline (Week 0) to Weeks 12, 24, 36 and 48
measure: Part A: Incidence of adverse event (AE)
timeFrame: Week 0 to Week 48
measure: Part A: Incidence of serious adverse event (SAE)
timeFrame: Week 0 to Week 48
measure: Part A: Incidence of treatment emergent adverse event (TEAE)
timeFrame: Week 0 to Week 48
measure: Part A: Incidence of potentially clinically significant abnormality (PCSA) in laboratory tests
timeFrame: Week 0 to Week 48
measure: Part A: Plasma concentration of SAR443820
timeFrame: Up to Week 36
measure: Part B: Percent change from baseline in BVL as detected by brain MRI
timeFrame: From baseline (Week 0) to Week 96
measure: Part B: Change from baseline in the volume of slowly expanding lesions (SELs)
timeFrame: From baseline (Week 0) to Weeks 96
measure: Part B: Change from baseline in the number of SELs
timeFrame: From baseline (Week 0) to Weeks 96
measure: Part B: Change from baseline in the intensity (T1) of SELs
timeFrame: From baseline (Week 0) to Weeks 96
measure: Part B: Change from baseline in the normalized T1 intensity in lesions
timeFrame: From baseline (Week 0) to Weeks 96
measure: Part B: Change from baseline in the total number of non-enhancing lesions
timeFrame: From baseline (Week 0) to Weeks 96
measure: Part B: Change from baseline in the volume of non-enhancing lesions
timeFrame: From baseline (Week 0) to Weeks 96
measure: Part B: Change from baseline in the number of PRLs (same participants/centers from Part A with 3T capability)
timeFrame: From baseline (Week 0) to Weeks 96
measure: Part B: Incidence of AE
timeFrame: Week 48 to Week 96
measure: Part B: Incidence of SAE
timeFrame: Week 48 to Week 96
measure: Part B: Incidence of TEAE
timeFrame: Week 48 to Week 96
measure: Part B: Incidence of potentially clinically significant abnormality (PCSA) in laboratory tests
timeFrame: Week 48 to Week 96
measure: Part B: Incidence of PCSA in ECG
timeFrame: Week 48 to Week 96
measure: Part B: Incidence of PCSA in vital signs
timeFrame: Week 48 to Week 96
measure: Part B: Cumulative number of new Gd-enhancing lesions as detected by T1-weighted MRI
timeFrame: Week 48 to Week 96
measure: Part B: number of new or enlarging T2-hyperintense lesions on MRI
timeFrame: Week 48 to Week 96
measure: Part B: ARR of RMS population (relapsing SPMS and RRMS)
timeFrame: Up to Week 96
measure: Part B: Time to onset of composite CDP (CCDP), confirmed over at least 12 weeks (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-HPT)
timeFrame: Up to Week 96
measure: Part B: Time to onset of 12 weeks CDP as assessed by the EDSS score
timeFrame: Up to Week 96
measure: Part B: Time to onset of sustained 20% increase in 9-HPT confirmed over at least 12 weeks
timeFrame: Up to Week 96
measure: Part B: Time to onset of sustained 20% increase T25-FW test confirmed over at least 12 weeks
timeFrame: Up to Week 96
measure: Part B: Change from baseline in EDSS Plus
timeFrame: From baseline (Week 0) to Week 96
measure: Part B: Change in Multiple Sclerosis Impact Scale -29 version 2 (MSIS-29v2) physical and psychological domains scoring
timeFrame: From baseline (Week 0) to Week 96
measure: Part B: Change in Multiple Sclerosis Walking Scale 12 items (MSWS-12
timeFrame: From baseline (Week 0) to Week 96
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: Investigational Site Number : 0560001
city: Gent
country: Belgium
facility: Investigational Site Number : 0560002
city: Overpelt
country: Belgium
facility: Investigational Site Number : 0560003
city: Sofia
country: Bulgaria
facility: Investigational Site Number : 1000001
city: Sofia
country: Bulgaria
facility: Investigational Site Number : 1000002
city: Sofia
country: Bulgaria
facility: Investigational Site Number : 1000003
city: Ottawa
country: Canada
facility: Investigational Site Number : 1240002
state: Ontario
city: Toronto
country: Canada
facility: Investigational Site Number : 1240004
state: Ontario
city: Gatineau
country: Canada
facility: Investigational Site Number : 1240001
state: Quebec
city: Levis
country: Canada
facility: Investigational Site Number : 1240003
state: Quebec
city: Santiago
country: Chile
facility: Investigational Site Number : 1520001
state: Reg Metropolitana De Santiago
city: Chengdu
country: China
facility: Investigational Site Number : 1560003
city: Shanghai
country: China
facility: Investigational Site Number : 1560002
city: Tianjin
country: China
facility: Investigational Site Number : 1560001
city: Xi'an
country: China
facility: Investigational Site Number : 1560004
city: Caen
country: France
facility: Investigational Site Number : 2500004
city: Nice
country: France
facility: Investigational Site Number : 2500002
city: Paris
country: France
facility: Investigational Site Number : 2500001
city: Strasbourg
country: France
facility: Investigational Site Number : 2500003
city: Würzburg
country: Germany
facility: Investigational Site Number : 2760002
city: Pozzilli
country: Italy
facility: Investigational Site Number : 3800001
state: Isernia
city: Cagliari
country: Italy
facility: Investigational Site Number : 3800005
city: Milano
country: Italy
facility: Investigational Site Number : 3800002
city: Milano
country: Italy
facility: Investigational Site Number : 3800003
city: Katowice
country: Poland
facility: Investigational Site Number : 6160002
state: Slaskie
city: Katowice
country: Poland
facility: Investigational Site Number : 6160005
state: Slaskie
city: Plewiska
country: Poland
facility: Investigational Site Number : 6160004
state: Wielkopolskie
city: Krakow
country: Poland
facility: Investigational Site Number : 6160001
city: Zabrze
country: Poland
facility: Investigational Site Number : 6160006
city: Sevilla
country: Spain
facility: Investigational Site Number : 7240002
state: Andalucia
city: Barcelona
country: Spain
facility: Investigational Site Number : 7240001
state: Barcelona [Barcelona]
city: Madrid / Madrid
country: Spain
facility: Investigational Site Number : 7240004
state: Madrid, Comunidad De
city: Madrid
country: Spain
facility: Investigational Site Number : 7240003
state: Madrid, Comunidad De
city: Madrid
country: Spain
facility: Investigational Site Number : 7240006
city: Murcia
country: Spain
facility: Investigational Site Number : 7240005
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: