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

• Register: ClinicalTrials.gov
• Last refreshed on: 18 November 2024
• Main ID: NCT04572841
• Date of registration: 28/09/2020
• Prospective Registration: Yes
• Primary sponsor: Sanofi
• Public title: Safety, Tolerability, Pharmacokinetics, and Therapeutic Efficacy of SAR441344 in Primary Sjögren's Syndrome (pSjS) phaethuSA
• Scientific title: A Randomized, Double-blind, Placebo-controlled, Parallel-group Study of the Safety, Tolerability, Pharmacokinetics, and Therapeutic Efficacy of SAR441344 in Adult Patients With Primary Sjögren's Syndrome (pSjS)
• Date of first enrolment: November 12, 2020
• Target sample size: 84
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT04572841
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

Argentina, Belgium, Canada, Chile, France, Germany, Hungary, Korea, Republic of, Mexico, Spain, Taiwan, United States

Contacts

• Name: Clinical Sciences & Operations
• Affiliation: Sanofi

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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.

Exclusion Criteria:

- 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.

- Clinically significant multiple or severe drug allergies, intolerance to topical
corticosteroids, or severe post treatment hypersensitivity reactions (including, but
not limited to, erythema multiforme major, linear IgA dermatosis, toxic epidermal
necrolysis, and exfoliative dermatitis).

- Any prior history of malignancy or active malignancy, including lymphoproliferative
diseases and lymphoma (except successfully treated carcinoma in situ of the cervix,
nonmetastatic squamous cell or basal cell carcinoma of the skin) within 5 years
prior to Baseline.

- Unstable dose of nonsteroidal anti inflammatory drugs (NSAIDs) and/or unstable use
of topical and/or pharmacological stimulant treatment for salivary and lacrimal
glands 4 weeks before Screening.

- High dose steroids, or a change in steroid dose within 4 weeks prior to Day
1/Randomization or expected changes during the course of the study.

- High dose of hydroxychloroquine or chloroquine, or methotrexate or change in
hydroxychloroquine, chloroquine or methotrexate dose within 12 weeks prior to Day
1/Randomization or expected changes during the course of the study.

- Participants treated with the following medications/procedures prior to Screening:

- Previous treatment with azathioprine and other thiopurines, mycophenolate
mofetil, sulfasalazine, or cyclosporine A within 3 months.

- Previous treatment with cyclophosphamide, leflunomide, or belimumab within 6
months.

- Previous treatment with rituximab within 12 months.

- Previous bone marrow transplantation, total lymphoid irradiation or ablative
ultra high dose cyclophosphamide or IV Ig.

- Previous treatment with any other biologic drug within 5 times the half life of
the drug.

- Received administration of any live (attenuated) vaccine within 3 months prior to
Day 1/Randomization (eg, varicella zoster vaccine, oral polio, rabies).

- Clinically significant abnormal ECG or vital signs at Screening.

- Abnormal laboratory test(s) at Screening.

- Positive human immunodeficiency virus (HIV) serology (anti HIV1 and anti HIV2
antibodies) or a known history of HIV infection, active or in remission.

- Positive result on any of the following tests: hepatitis B surface antigen (HBsAg),
anti hepatitis B core antibodies (anti HBc Ab), anti hepatitis C virus antibodies
(HCV-Ab).

- If female, pregnant and/or breastfeeding.

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


Age minimum: 18 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

Sjögren's Syndrome

Sjogren's Syndrome

Intervention(s)

Drug: SAR441344

Drug: Placebo

Primary Outcome(s)

Change in ESSDAI [Time Frame: Baseline to Week 12]

Secondary Outcome(s)

Change in the EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) [Time Frame: Baseline to Week 12]

Incidence of study investigational medicinal product (IMP) discontinuation and withdrawals due to TEAEs [Time Frame: Baseline to Week 24]

Change in the Multidimensional Fatigue Inventory (MFI) general fatigue subscale and other subscales [Time Frame: Baseline to Week 12]

Incidence of AEs related to local tolerability findings [Time Frame: Baseline to Week 12]

Assessment of PK parameter: Cmax [Time Frame: Baseline to Week 12]

Change in participant reported local tolerability scale [Time Frame: Baseline to Week 12]

Participants with medically significant changes in vital signs, electrocardiogram, and/or laboratory evaluations [Time Frame: Baseline to Week 12]

Antidrug antibodies [Time Frame: Baseline to Week 24]

Assessment of PK parameter: t1/2z [Time Frame: Baseline to Week 12]

Assessment of PK parameter: AUC0-tau [Time Frame: Baseline to Week 12]

Assessment of PK parameter: tmax [Time Frame: Baseline to Week 12]

Descriptive statistics of SAR441344 concentrations [Time Frame: Baseline to Week 12]

Incidence of treatment emergent AEs (TEAEs), serious AEs (SAEs), and AEs of special interest (AESIs) [Time Frame: Baseline to Week 24]

Secondary ID(s)

2020-000511-77

ACT16618

U1111-1244-2266

Source(s) of Monetary Support

Please refer to primary and secondary sponsors