A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, Dose-ranging Study to Evaluate the Efficacy and Safety of Abiprubart in Participants with Sjögren’s Disease

Prior treatment

• Prior exposure to any other anti-CD40/CD154 agent.
• Injectable corticosteroids (including intra-articular) within 8 weeks prior to randomization. (Note: Concomitant-treatment with nonsteroidal anti-inflammatory drugs, acetaminophen, oral corticosteroids [equivalent to prednisone ≤ 10 mg/day], or inhaled corticosteroids at a stable dose ≥ 4 weeks prior to baseline for stable medical conditions is allowed and should be kept at a stable dose throughout the study).
• Has started, stopped or adjusted dose/regimen of medications for treatment of, or known to cause, dry mouth/eyes (such as sialagogues, artificial saliva, artificial tears, other topical ophthalmologic agents, antihistamines, antidepressants, anticholinergics, sedatives, antipsychotic drugs, or anti-Parkinson agents), within the 30 days prior to screening or is anticipating change to these treatment regimens during the study.
• Has history of immunodeficiency (e.g., immune disorders or disorders that result in decreased immunity), including human immunodeficiency virus (HIV). HIV test will be performed during screening unless participant has a previously documented negative HIV result within 8 weeks prior to Screening.
• Has received immunization with a live (attenuated) vaccine within 4 weeks prior to randomization or is expected to receive live (attenuated) vaccine during the study or within 6 weeks after the last study drug administration.
• Has any prior history of lymphoid malignancy associated with Sjögren’s Disease diagnosis.
• Has received cataract surgery, Lasik, or other ophthalmologic surgery procedure (e.g., lachrymal plug) in the 6 months prior to Screening.

Other illness

• Positive or indeterminate results for hepatitis C virus infection or chronic active hepatitis B infection (at Screening) as defined below: a. Hepatitis C antibody positive b. Hepatitis B surface antigen positive c. Hepatitis B anti-core antibody positive but anti-surface antibody negative
• History of thromboembolic event or a significant risk of future thromboembolic events (defined as a definitive diagnosis of thrombophilia OR an ongoing condition associated with an increased incidence of intravascular thrombosis, such as atrial fibrillation or anti-phospholipid syndrome). All history of intravascular thrombosis should be approved by the medical monitor.
• Diagnosis of Sjögren’s Disease overlap syndromes where another autoimmune rheumatic disease constitutes the principal illness, including fibromyalgia with currently active, inadequately controlled symptoms.
• Concurrent or prior disease modifying treatments prior to study treatment period defined in the table within protocol section 4.2

Lab values

• Positive (or 2 indeterminate) QuantiFERON® test results unless confirmation of prior completion of appropriate treatment for latent TB and no evidence of active TB – QuantiFERON TB-Gold (QFT) testing should be performed through the central laboratory. QFT testing may be performed by a local laboratory with approval from the medical monitor. QFT test will be performed during screening unless participant has a previously documented negative QFT result within 8 weeks prior to Screening or documented prior positive QFT at any time. – An indeterminate QFT test should be repeated. – A positive QFT test or two successive indeterminate QFT results should be considered a positive diagnostic TB test. – An indeterminate QFT test followed by a negative QFT test should be considered a negative diagnostic TB test. – When possible, QFT test should be performed at least 4 weeks after receiving an mRNA COVID-19 vaccine.
  • A full list of exclusion criteria can be found in the current protocol.

Other

• Is currently enrolled in another clinical study (at the time of Screening), with the exception of observational studies.

• Is capable of understanding the written ICF, has provided signed written informed consent, and agrees to comply with protocol requirements.
• Has stimulated whole salivary flow rate at Screening of ≥ 0.05 mL/min.
• Weighs at least 40 kg and no more than 150 kg and has a body mass index (BMI) within the range of 18-40 kg/m2.
• Routine adult vaccinations, including COVID-19, influenza, pneumonia, and zoster, should be up to date and/or vaccines offered at least 2 weeks prior to randomization according to regional and national guidelines based on medical history or presence of risk factors, in the opinion of the Investigator.
• [Original Criterion deleted]
  • A full list of inclusion criteria can be found in the current protocol.
• If female, must be either postmenopausal (defined as no menses for 12 months without other medical cause), permanently surgically sterile (i.e., removal of ovaries, fallopian tubes, and/or uterus), or, for women of childbearing potential, must: a. Be nonpregnant, nonlactating, and agree to remain abstinent or use a method of contraception with a failure rate of < 1% per year from the screening visit until after the EOS visit. Examples of contraception methods with a failure rate of < 1% per year include: i. hormonal contraceptives associated with inhibition of ovulation (stable dose for at least 4 weeks prior to first dose of study drug); hormonal contraceptive methods must be supplemented by a barrier method ii. hormone-releasing or copper intrauterine device iii. bilateral tubal occlusion iv. vasectomized male partner v. abstinence from heterosexual intercourse; the reliability of sexual abstinence should be evaluated based on duration of the study and usual lifestyle of the participant. Intermittent abstinence (such as calendar, ovulation, symptothermal or postovulation) and withdrawal are not considered acceptable contraceptive methods b. The definition of childbearing potential may be adapted for alignment with local guidelines or regulations
• Sexually active male participants must have documented vasectomy or must agree to use a condom or method of contraception with a failure rate of <1% per year, as defined above with their partners of childbearing potential from first dose of study drug until after the EOS visit.
• Male participants must agree to refrain from donating sperm from first dose of study drug until 30 days after the last study drug administration. Female participants must agree to refrain from donating eggs from first dose of study drug until after the EOS visit.
• Females of childbearing potential must have a negative serum β-human chorionic gonadotropin test during screening and negative urine pregnancy test on Day 1.
• Is male or female at birth, and > 18 years of age and < 81 years of age at Screening.
• Has a diagnosis of Sjögren’s Disease according to 2016 ACR-EULAR Classification Criteria.
• Has ESSDAI value ≥ 5, counting only the biological, hematological, articular, cutaneous, glandular, lymphadenopathy, and constitutional organ domains at Screening.
• Is seropositive at Screening for anti-SSA antibodies tested at a central laboratory.