Trial of Sibeprenlimab in the Treatment of Sjögren’s Disease

Prior treatment

• Use of topical ocular prescription medications (excluding artificial tears, gels, lubricants) that have not been on a stable dose for at least 90 days prior to randomization, or any anticipated change in the treatment regimen during the course of the trial
• Evidence of active tuberculosis infection is exclusionary. Participant with previously treated tuberculosis and previously treated or newly diagnosed latent tuberculosis may be eligible
• Participant who has a recent history (ie, within the past year) of alcohol or drug/chemical abuse that would, based on the investigator’s clinical judgment, interfere with the participant’s ability to participate in the trial
• Participants who would be likely to require prohibited concomitant therapy during the trial
• Prior treatment with any of the following within 6 months prior to randomization: belimumab, abatacept, anti-tumor necrosis factor alpha biologic agents, immunoglobulins, plasmapheresis; intravenous (IV) or oral cyclophosphamide, mycophenolate mofetil, IV or oral cyclosporine A or any other immunosuppressants not specified in the protocol
• Use of other investigational drugs within 5 half-lives of enrollment, or within 30 days or until the expected pharmacodynamic effect has returned to baseline, whichever is longer
• History of a previous hypersensitivity or severe allergic reaction with generalized urticaria, angioedema, or anaphylaxis to any of the ingredients of the sibeprenlimab SC injection formulation
• Regular use of medications known to cause dry mouth/eyes as a regular and major side effect, and which have not been on a stable dose for at least 30 days prior to screening, or any anticipated change in the treatment regimen during the course of the trial

Other illness

• Presence of another autoimmune rheumatic disease that is active and constitutes the principal illness
• History of primary or secondary immunodeficiency, including a positive human immunodeficiency virus (HIV) test result
• History of malignancy of any organ system (other than basal cell carcinoma of the skin or in situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases
• Any history of head and neck radiation treatment
• History of sarcoidosis
• Any surgical, medical (eg, uncontrolled hypertension, heart failure, cerebrovascular accident), psychiatric or additional physical condition that the sponsor, medical monitor, and/or investigator feels may jeopardize the participant in case of participation in this trial
• Positive serology for hepatitis B surface antigen
• Participants with a known history of noncompliance to medication, or who were unable or unwilling to complete patient-reported outcome questionnaires, or who are unable or unwilling to use the device for collection of patient-reported outcomes
• Active viral, bacterial, or other infections requiring systemic treatment at the time of screening or randomization, or history of recurrent clinically significant infection
• History of major organ, hematopoietic stem cell, or bone marrow transplant

Lab values

• Participant has uncontrolled type 2 diabetes, as evidenced by a screening hemoglobin A1c (HbA1c) value > 8%. Participant will be excluded if their antidiabetic regimen is not stable. A stable antidiabetic regimen is defined as either diet and exercise therapy alone or in combination with any approved antidiabetic medication in which the doses of oral or noninsulin injectable medications have not changed during the 8 weeks prior to enrollment; or the doses of long-acting insulin or intermediate-acting insulin have not varied by more than 20% during the 8 weeks prior to enrollment
• Hepatitis C: participants with positive hepatitis C antibody and hepatitis C virus (HCV)-ribonucleic acid (RNA) at screening are excluded. Chronic hepatitis C participants who have completed HCV antiviral treatment must be HCV-RNA negative at least 12 weeks after treatment before randomization to be eligible. Cases of spontaneous HCV clearance should be discussed with the sponsor before enrollment
• Prior use of a B-cell depleting therapy within 12 months prior to randomization; if the CD19 count has returned to the baseline value prior to receipt of the B-cell depleting therapy, or at a normal reference value, as early as 9 months since the therapy, the patient may be eligible if the B-cell count is greater than: the lower limit of normal or baseline value prior to receipt of previous B cell-depleting therapy (whichever is greater) at screening
• Any one of the following laboratory values at screening. Hematologic abnormalities below these reference values will be reviewed by the Medical Monitor and investigator to determine whether the values are attributable to Sjögren’s disease. If the abnormalities are attributable to Sjögren’s disease, the participant may be enrolled. a) Hemoglobin levels < 8.0 g/dL b) White blood cells (WBC) count < 4.0 × 103/μL c) Platelet count < 100 × 103/μL d) Absolute neutrophil count (ANC) < 1.0 × 103/μL e) eGFR calculated using the 2021 Chronic Kidney Disease-Epidemiology Collaboration serum creatinine eGFR formula < 45 mL/min/1.73 m2

Other

• Presence of active fibromyalgia
• Pregnant or nursing (lactating) women
• Heterosexually active biological males or participants of childbearing potential, or their partners, who do not agree to adhere to use 2 forms of highly effective contraceptives from the time of consent through the end of the participant’s participation in the trial and for an additional 90 days (biological male participants) or 30 days (biological female participants) thereafter
• Biological male participants who do not agree to avoid donation of sperm from the time of consent through the end of the participant’s participation in the trial and an additional 90 days thereafter
• Participant is judged by the investigator or the medical monitor to be inappropriate for the trial

• Signed informed consent must be obtained prior to participation in the trial
• Participants taking systemic corticosteroids have to be on a stable dose of ≤ 10 mg/day prednisone/prednisolone or equivalent for at least 30 days before randomization
• Ability to provide written informed consent prior to initiation of any trial-specific procedures, and ability, in the opinion of the principal investigator, to comply with all the requirements of the trial
• Participants between 18 to 75 years of age
• Classification of Sjögren’s disease according to the 2016 American College of Rheumatology (ACR)/EULAR criteria
• Seropositive for anti-Ro52 and/or anti-Ro60 antibodies at screening
• Screening ESSDAI score ≥ 5; activity in the pulmonary, central nervous system, or peripheral nervous system domains will not be counted towards the qualifying screening ESSDAI score
• Stimulated whole salivary flow rate of ≥ 0.05 mL/min at screening
• Serum IgG > 900 mg/dL as assessed prospectively by a central laboratory test
• Ability to communicate well with the investigator, understand and agree to comply with the requirements of the trial
• Participants may be on hydroxychloroquine (≤ 400 mg/day), methotrexate (≤ 25 mg/week), leflunomide (≤ 20 mg daily), or azathioprine (≤ 150 mg/day) if the participant has been on a stable and well-tolerated dose for at least 30 days before randomization