Safety, Tolerability, Pharmacokinetics, and Therapeutic Efficacy of SAR441344 in Primary Sjögren's Syndrome (pSjS)

NCT04572841 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: ACT16618U1111-1244-22662020-000511-77
• Study Type: interventional
• Target: 84
• Locations: 12 countries
• Sites: 36

Brief Summary

Primary Objective: To evaluate the therapeutic efficacy of one dose level of SAR441344 versus placebo over 12 weeks in adult patients with primary Sjögren's syndrome (pSjS), assessed by the change of the European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) Secondary Objectives:

• To evaluate the therapeutic efficacy of one dose level of SAR441344 versus placebo over 12 weeks in adult patients with pSjS
• To evaluate the therapeutic efficacy on fatigue of one dose level of SAR441344 versus placebo over 12 weeks in adult patients with pSjS
• To evaluate the pharmacokinetic (PK) exposure of one dose level of SAR441344 over 12 weeks in adult patients with pSjS
• To evaluate the safety and tolerability of one dose level of SAR441344 versus placebo in adult patients with pSjS as determined by adverse events (AEs)
• To evaluate the local tolerability of one dose level of SAR441344 versus placebo over 12 weeks in adult patients with pSjS
• To evaluate the safety and tolerability of one dose level of SAR441344 versus placebo over 12 weeks in adult patients with pSjS determined by electrocardiogram, vital signs, and laboratory evaluations
• To measure the immunogenicity of one dose level of SAR441344 versus placebo over 12 weeks in adult patients with pSjS This is a multicenter, randomized, double blind, placebo controlled, parallel group proof of concept Phase 2 study to evaluate the therapeutic efficacy of SAR441344 in adult patients with primary Sjögren's syndrome (pSjS), as well as safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD).
• Study visit frequency: every 2 weeks in the treatment period and every 4 weeks in the follow-up period.
• The total duration of the study will be 24 weeks (28 weeks including maximum screening duration) for each participant, including a 12-week treatment period and a 12-week follow-up period.

Conditions

Sjögren's Syndrome; Sjogren's Syndrome

Outcome Measures

Primary Outcomes (1)

• Change From Baseline to Week 12 in ESSDAI Score

  ESSDAI is validated and established outcome measurement for therapeutic efficacy in Sjögren's syndrome, evaluating disease activity mainly on extra-glandular manifestations. This score consists of 12 organ-specific domains (constitutional, lymphadenopathy, glandular, articular, cutaneous, pulmonary, renal, muscular, peripheral and central nervous system, hematological, biological), which are scored based on organ-specific items in 3 to 4 different severity grades (no, low, moderate, high; with 0=no and 3=high). These scores are summed up over all 12 domains in weighted way (severity grades are multiplied with weights ranging 1-6 depending on domain) to summarize into total score(0-123). Higher scores indicates worse outcome. Negative change from baseline indicates improvement. Baseline=Day 1 assessment value. Least squares (LS) mean is calculated using mixed models for repeated measures (MMRM). Observed values after occurrence of intercurrent events are excluded.

  Baseline (Day 1) to Week 12

Secondary Outcomes (18)

• Change From Baseline to Week 12 in European League Against Rheumatism (EULAR) Sjögren's Syndrome Patient Reported Index (ESSPRI) Score

  Baseline (Day 1) to Week 12

• Change From Baseline to Week 12 in Multidimensional Fatigue Inventory (MFI) General Fatigue Subscale and Other Subscales Score

  Baseline (Day 1) to Week 12

• Mean Plasma Concentration of SAR441344

  At end of infusion and 4 hours post-infusion on Day 1; pre-dose at Weeks 2, 4, 6, 8, 10, and at Week 12

• Median Plasma Concentration of SAR441344

  At end of infusion and 4 hours post-infusion on Day 1; pre-dose at Weeks 2, 4, 6, 8, 10, and at Week 12

• Maximum Plasma Concentration (Cmax) of SAR441344

  After the last SC dose on Week 10 up to 336 hours post-dose

Study Arms (2)

SAR441344

EXPERIMENTAL

SAR441344 single intravenous (IV) loading dose on Day 1 followed by a single subcutaneous (SC) dose administered once every 2 weeks from Week 2 to Week 10 (5 administrations)

Drug: SAR441344

Placebo

PLACEBO COMPARATOR

Matching placebo

Drug: Placebo

Interventions

SAR441344 DRUG

Pharmaceutical form: solution for injection Route of administration: intravenous or subcutaneous

SAR441344

Placebo DRUG

Pharmaceutical form: solution for injection Route of administration: intravenous or subcutaneous

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must be 18 to 80 years of age inclusive, at the time of signing the informed consent.
• Diagnosis of pSjS according to the American College of Rheumatology/EULAR 2016 criteria at Screening.
• Disease duration since first diagnosis of pSjS ≤15 years based on medical history.
• Participants with moderate to severe disease activity set with ESSDAI total score ≥5, based on the following domains at Screening: glandular, articular, muscular, hematological, biological, and constitutional, lymphadenopathy.
• Seropositive for anti-Ro/SSA antibodies.
• IgG \> lower limit of normal (ULN) at Screening.
• Stimulated salivary flow rate of ≥0.1 mL/min at Screening or Baseline.
• Body weight within 45 to 120 kg (inclusive) and body mass index within the range of 18.0 to 35.0 kg/m2 (inclusive) at Screening.
• Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Capable of giving signed informed consent.

You may not qualify if:

• Any autoimmune disease (except pSjS and Hashimoto thyroiditis) with or without secondary SjS.
• History, clinical evidence, suspicion or significant risk for thromboembolic events, as well as myocardial infarction, stroke, and/or antiphospholipid syndrome and any participants requiring antithrombotic treatment.
• Active life threatening or organ threatening complications of pSjS disease at the time of Screening based on treating physician evaluation including but not restricted to:
• Vasculitis with renal, digestive, cardiac, pulmonary, or CNS involvement characterized as severe,
• Active central nervous system (CNS) or peripheral nervous system (PNS) involvement requiring high dose steroids,
• Severe renal involvement defined by objective measures,
• Lymphoma.
• Cardiac heart failure Stage III or IV according to the New York Heart Association.
• Severe pulmonary impairment documented by an abnormal pulmonary function test.
• Serious systemic viral, bacterial or fungal infection (eg, pneumonia, pyelonephritis), infection requiring hospitalization or IV antibiotics or significant chronic viral (including history of recurrent or active herpes zoster), bacterial, or fungal infection (eg, osteomyelitis) 30 days before and during Screening.
• Participants with a history of invasive opportunistic infections, such as, but not limited to histoplasmosis, listeriosis, coccidioidomycosis, candidiasis, pneumocystis jirovecii, and aspergillosis, regardless of resolution.
• Evidence of active or latent tuberculosis (TB) as documented by medical history (eg, chest X rays) and examination, and TB testing: A positive or 2 indeterminate QuantiFERON® TB Gold tests at Screening (regardless of prior treatment status).
• Evidence of any clinically significant, severe or unstable, acute or chronically progressive, uncontrolled infection or medical condition (eg, cerebral, cardiac, pulmonary, renal, hepatic, gastrointestinal, neurologic, or any known immune deficiency) or previous, active or pending surgical disorder, or any condition that may affect participant safety in the judgment of the Investigator (including vaccinations which are not updated based on local regulation).
• History or presence of diseases which exclude diagnosis of SjS as per the American College of Rheumatology/EULAR 2016 criteria including, but not limited to, sarcoidosis, amyloidosis, graft-versus-host disease, IgG4 related disease, and history of head and neck radiation treatment.
• History of systemic hypersensitivity reaction or significant allergies, other than localized injection site reaction, to any humanized monoclonal antibody.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (36)

Omega Research Consultants Debary Site Number : 8400005

DeBary, Florida, 32713, United States

Location

Altoona Center For Clinical Research Site Number : 8400001

Duncansville, Pennsylvania, 16635, United States

Location

Ramesh C. Gupta, M.D. Site Number : 8400007

Memphis, Tennessee, 38119, United States

Location

Prolato Clinical Research Center Site Number : 8400009

Houston, Texas, 77054, United States

Location

Investigational Site Number : 0320004

CABA, Buenos Aires, 1430, Argentina

Location

Investigational Site Number : 0320002

CABA, Buenos Aires, C1111, Argentina

Location

Investigational Site Number : 0320003

Pergamino, Buenos Aires, B2700CPM, Argentina

Location

Investigational Site Number : 0320001

San Miguel de Tucumán, Tucumán Province, T4000AXL, Argentina

Location

Investigational Site Number : 0560002

Ghent, 9000, Belgium

Location

Investigational Site Number : 0560001

Leuven, 3000, Belgium

Location

Investigational Site Number : 1240001

Sherbrooke, Quebec, J1L 0H8, Canada

Location

Investigational Site Number : 1520002

Osorno, Los Lagos Region, 5311092, Chile

Location

Investigational Site Number : 1520001

Santiago, Reg Metropolitana de Santiago, 7640881, Chile

Location

Investigational Site Number : 1520004

Viña del Mar, Región de Valparaíso, 2520598, Chile

Location

Investigational Site Number : 2500003

Limoges, 87042, France

Location

Investigational Site Number : 2500005

Marseille, 13003, France

Location

Investigational Site Number : 2500001

Montpellier, 34295, France

Location

Investigational Site Number : 2500004

Paris, 75010, France

Location

Investigational Site Number : 2500006

Paris, 75013, France

Location

Investigational Site Number : 2500002

Strasbourg, 67098, France

Location

Investigational Site Number : 2760001

Berlin, 10117, Germany

Location

Investigational Site Number : 3480003

Budapest, 1036, Hungary

Location

Investigational Site Number : 3480001

Debrecen, 4032, Hungary

Location

Investigational Site Number : 3480004

Székesfehérvár, 8000, Hungary

Location

Investigational Site Number : 4840002

Mexicali, Estado de Baja California, 21200, Mexico

Location

Investigational Site Number : 4840001

Monterrey, Nuevo León, 64460, Mexico

Location

Investigational Site Number : 4840003

Chihuahua City, 31020, Mexico

Location

Investigational Site Number : 4100004

Daegu, Daegu, 561-712, South Korea

Location

Investigational Site Number : 4100002

Seoul, Seoul-teukbyeolsi, 03080, South Korea

Location

Investigational Site Number : 4100001

Seoul, 06591, South Korea

Location

Investigational Site Number : 7240003

Seville, Andalusia, 41010, Spain

Location

Investigational Site Number : 7240002

Málaga, 29010, Spain

Location

Investigational Site Number : 1580002

Taichung, 40447, Taiwan

Location

Investigational Site Number : 1580003

Tainan, 704, Taiwan

Location

Investigational Site Number : 1580001

Taipei, 100, Taiwan

Location

Investigational Site Number : 1580005

Taoyuan, 33305, Taiwan

Location

Related Links

• ACT16618 Plain Language Results Summary

MeSH Terms

Conditions

Sjogren's Syndrome

Condition Hierarchy (Ancestors)

Arthritis, Rheumatoid; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Xerostomia; Salivary Gland Diseases; Mouth Diseases; Stomatognathic Diseases; Dry Eye Syndromes; Lacrimal Apparatus Diseases; Eye Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2020
• First Posted: October 1, 2020
• Study Start: November 12, 2020
• Primary Completion: November 8, 2023
• Study Completion: February 9, 2024
• Last Updated: October 9, 2025
• Results First Posted: October 9, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

BE (2); ME (3); FR (6); US (4); HU (3); CL (3); CA (1); KR (3); ES (2); TW (4); DE (1); AR (4)