Clinical trial NCT04572841: Safety, Tolerability, Pharmacokinetics, and Therapeutic Efficacy of SAR441344 in Primary Sjögren's Syndrome (pSjS)
Official 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sjögren's Syndrome
Sjogren's Syndrome
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2020-10-01
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Change in ESSDAI
timeFrame: Baseline to Week 12
Secondary outcomes:
measure: Change in the EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI)
timeFrame: Baseline to Week 12
measure: Change in the Multidimensional Fatigue Inventory (MFI) general fatigue subscale and other subscales
timeFrame: Baseline to Week 12
measure: Descriptive statistics of SAR441344 concentrations
timeFrame: Baseline to Week 12
measure: Assessment of PK parameter: Cmax
timeFrame: Baseline to Week 12
measure: Assessment of PK parameter: tmax
timeFrame: Baseline to Week 12
measure: Assessment of PK parameter: AUC0-tau
timeFrame: Baseline to Week 12
measure: Assessment of PK parameter: t1/2z
timeFrame: Baseline to Week 12
measure: Incidence of treatment emergent AEs (TEAEs), serious AEs (SAEs), and AEs of special interest (AESIs)
timeFrame: Baseline to Week 24
measure: Incidence of study investigational medicinal product (IMP) discontinuation and withdrawals due to TEAEs
timeFrame: Baseline to Week 24
measure: Change in participant reported local tolerability scale
timeFrame: Baseline to Week 12
measure: Incidence of AEs related to local tolerability findings
timeFrame: Baseline to Week 12
measure: Participants with medically significant changes in vital signs, electrocardiogram, and/or laboratory evaluations
timeFrame: Baseline to Week 12
measure: Antidrug antibodies
timeFrame: Baseline to Week 24
Other outcomes:
Locations:
city: DeBary
country: United States
facility: Omega Research Consultants Debary Site Number : 8400005
state: Florida
city: Duncansville
country: United States
facility: Altoona Center For Clinical Research Site Number : 8400001
state: Pennsylvania
city: Memphis
country: United States
facility: Ramesh C. Gupta, M.D. Site Number : 8400007
state: Tennessee
city: Houston
country: United States
facility: Prolato Clinical Research Center Site Number : 8400009
state: Texas
city: Caba
country: Argentina
facility: Investigational Site Number : 0320004
state: Buenos Aires
city: Caba
country: Argentina
facility: Investigational Site Number : 0320002
state: Buenos Aires
city: Pergamino
country: Argentina
facility: Investigational Site Number : 0320003
state: Buenos Aires
city: San Miguel de Tucuman
country: Argentina
facility: Investigational Site Number : 0320001
state: Tucumán
city: Gent
country: Belgium
facility: Investigational Site Number : 0560002
city: Leuven
country: Belgium
facility: Investigational Site Number : 0560001
city: Sherbrooke
country: Canada
facility: Investigational Site Number : 1240001
state: Quebec
city: Osorno
country: Chile
facility: Investigational Site Number : 1520002
state: Los Lagos
city: Santiago
country: Chile
facility: Investigational Site Number : 1520001
state: Reg Metropolitana De Santiago
city: Viña del Mar
country: Chile
facility: Investigational Site Number : 1520004
state: Valparaíso
city: Limoges
country: France
facility: Investigational Site Number : 2500003
city: Marseille
country: France
facility: Investigational Site Number : 2500005
city: Montpellier
country: France
facility: Investigational Site Number : 2500001
city: Paris
country: France
facility: Investigational Site Number : 2500004
city: Paris
country: France
facility: Investigational Site Number : 2500006
city: Strasbourg
country: France
facility: Investigational Site Number : 2500002
city: Berlin
country: Germany
facility: Investigational Site Number : 2760001
city: Budapest
country: Hungary
facility: Investigational Site Number : 3480003
city: Debrecen
country: Hungary
facility: Investigational Site Number : 3480001
city: Székesfehérvár
country: Hungary
facility: Investigational Site Number : 3480004
city: Daegu
country: Korea, Republic of
facility: Investigational Site Number : 4100004
state: Daegu-gwangyeoksi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100002
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100001
city: Mexicali
country: Mexico
facility: Investigational Site Number : 4840002
state: Baja California
city: Monterrey
country: Mexico
facility: Investigational Site Number : 4840001
state: Nuevo León
city: Chihuahua
country: Mexico
facility: Investigational Site Number : 4840003
city: Sevilla
country: Spain
facility: Investigational Site Number : 7240003
state: Andalucia
city: Málaga
country: Spain
facility: Investigational Site Number : 7240002
city: Taichung
country: Taiwan
facility: Investigational Site Number : 1580002
city: Tainan
country: Taiwan
facility: Investigational Site Number : 1580003
city: Taipei
country: Taiwan
facility: Investigational Site Number : 1580001
city: Taoyuan County
country: Taiwan
facility: Investigational Site Number : 1580005
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: