Date

2025-06-25

Protocol

Protocol changed

Item Changed

Exclusion criteria

Previous Version

• Subject has secondary forms of IgAN as determined by the treating physician (eg, infection-associated IgAN or IgAN associated with hepatic cirrhosis) or Henoch-Sch?nlein purpura (IgA vasculitis). • Subject has coexisting chronic kidney disease, other than IgAN. • Subject has evidence of additional pathological findings in the kidney biopsy (eg, diabetic kidney disease, membranous nephropathy, or lupus nephritis). However, hypertensive vascular changes are acceptable. • Subject has kidney biopsy (of any vintage) with a MEST or MEST-C score of T2 or C2 from the Oxford IgAN classification schema. If MEST-scoring was not performed, the presence of > 50% tubulo-interstitial fibrosis, or crescents in 25% of glomeruli is exclusionary. o Note: this criterion does not apply to the exploratory cohort. • Subject has nephrotic syndrome, defined for this purpose as 24-hour urine protein 3.5 g with concurrent hypoalbuminemia (serum albumin < 2.5 g/dL), hyperlipidemia (total cholesterol > 350 mg/dL), and edema. Subjects with isolated nephrotic range proteinuria (> 3.5 g/day) will be eligible. • Subject has a history or current evidence of a serious and/or unstable cardiovascular, respiratory, gastrointestinal, hematologic, autoimmune, blood dyscrasias or other medical disorder, including psychiatric disorders, cirrhosis, or ongoing malignancy. History of minor skin cancers (not including melanoma) or o surgically treated, limited cervical carcinomas (ie, carcinoma in situ) may not be exclusionary per the discretion of the investigator. • History of a previous severe allergic reaction with generalized urticaria, angioedema, or naphylaxis. • Subject has a body mass index < 16 kg/m2. • Subject has a serum IgG value < 600 mg/dL at screening. • Subject has received an organ transplant (ie, solid or a bone marrow or hematologic stem cell transplantation). • Subject is currently receiving, or has received within 16 weeks prior to randomization, systemic immunosuppression (note: topical, ophthalmic, rectal, intra-articular, inhaled corticosteroids, and short courses [? 14 days] of oral/intravenous steroids are allowed). • Subject has participated in another interventional clinical trial and received another investigational drug within 30 days prior to the administration of IMP or 5 half-lives from last investigational drug administration, whichever is longer. • Subject has any chronic infectious disease (eg, chronic urinary tract infection; chronic sinusitis; bronchiectasis; active pulmonary or systemic tuberculosis; chronic viral hepatitis, such as hepatitis C or hepatitis B [defined as positive for hepatitis B surface antigen]; or human immunodeficiency virus infection). • Subject has acute infectious disease at the time of screening. • Subject has Type 1 diabetes. • Subject has uncontrolled Type 2 diabetes, as evidenced by a screening hemoglobin A1c (HbA1c) value > 8%. Subjects will be excluded if their anti-diabetic regimen is not stable. A stable anti-diabetic regimen is defined as either diet and exercise therapy alone or in combination with any approved anti-diabetic 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. • Subject has uncontrolled hypertension (defined as systolic blood pressure o 140 mmHg or diastolic blood pressure > 90 mmHg). • Subject is planning or scheduled to undergo a tonsillectomy within the time they would be enrolled in the trial. Prior tonsillectomy is acceptable (if greater than 6 months prior to screening). • Subject 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 subject’s ability to participate in the trial. Subjects receiving any of the prohibited medications within the specified periods or who would be likely to require prohibited concomitant therapy during the trial.

Next Version

1. Subjects who are breast-feeding and/or who have a positive pregnancy test result prior to receiving IMP. 2. Heterosexually active biological males or subjects of childbearing potential, or their partners, who do not agree to adhere to contraceptive requirements from the time of consent through the end of the subject’s participation in the trial and an additional 90 days (biological male subjects) or 30 days (biological female subjects) thereafter. 3. Biological male subjects who do not agree to avoid donation of sperm from the time of consent through the end of the subject’s participation in the trial and an additional 90 days thereafter. 4. Subject has secondary forms of IgAN as determined by the treating physician (eg, infection-associated IgAN or IgAN associated with hepatic cirrhosis) or Henoch-Sch?nlein purpura (IgA vasculitis). 5. Subject has coexisting chronic kidney disease, other than IgAN. 6. Subject has evidence of additional pathological findings in the kidney biopsy (eg, diabetic kidney disease, membranous nephropathy, or lupus nephritis). However, hypertensive vascular changes are acceptable. 7. Subject has kidney biopsy with a MEST or MEST-C score of T2 or C2 from the Oxford IgAN classification schema. If MEST-scoring was not performed, the presence of > 50% tubulo-interstitial fibrosis, or crescents in > 25% of glomeruli is exclusionary. Note: this criterion does not apply to the exploratory cohort. Note: The most recent kidney biopsy will take precedence for purposes of eligibility. 8. Subject has nephrotic syndrome, defined for this purpose as 24-hour urine protein > 3.5 g with concurrent hypoalbuminemia (serum albumin < 2.5 g/dL), hyperlipidemia (total cholesterol > 350 mg/dL), and edema. Subjects with isolated nephrotic range proteinuria (> 3.5 g/day) will be eligible. 9. Subject has a history or current evidence of a serious and/or unstable cardiovascular, respiratory, gastrointestinal, hematologic, autoimmune, blood dyscrasias or other medical disorder, including psychiatric disorders, cirrhosis, or ongoing malignancy. History of minor skin cancers (not including melanoma) or surgically treated, limited cervical carcinomas (ie, carcinoma in situ) may not be exclusionary per the discretion of the investigator. 10. 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. 11. Subject has a body mass index < 16 kg/m2. 12. Subject has a serum IgG value < 600 mg/dL at screening. 13. Subject has received an organ transplant (ie, solid or a bone marrow or hematologic stem cell transplantation). 14. Subject is currently receiving, or has received within 16 weeks prior to randomization, systemic immunosuppression (note: topical, ophthalmic, rectal, intra-articular, inhaled corticosteroids, and short courses [? 14 days] of oral/IV steroids are allowed). 15. Subject has participated in another interventional clinical trial and received another investigational drug within 30 days prior to the administration of IMP or 5 half-lives from last investigational drug administration, whichever is longer. 16. Subject has any chronic infectious disease (eg, chronic urinary tract infection; chronic sinusitis; bronchiectasis; active pulmonary or systemic tuberculosis; chronic viral hepatitis, such as hepatitis C or hepatitis B [defined as positive for hepatitis B surface antigen]; or human immunodeficiency virus infection). 17. Subject has acute infectious disease at the time of screening. Note: Enrollment can be considered if the acute infection has resolved within the screening window, defined as resolution of acute clinical signs, symptoms, and related clinical laboratory parameters. Consultation between the trial site investigator and the medical monitor and/or sponsor should occur in case of any questions. 18. Subject has Type 1 diabetes. 19. Subject has uncontrolled Type 2 diabetes, as evidenced by a screening hemoglobin A1c (HbA1c) value > 8%. Subjects will be excluded if their anti-diabetic regimen is not stable. A stable anti-diabetic regimen is defined as either diet and exercise therapy alone or in combination with any approved anti-diabetic 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. 20. Subject has uncontrolled hypertension (defined as systolic blood pressure > 140 mmHg or diastolic blood pressure > 90 mmHg). 21. Subject is planning or scheduled to undergo a tonsillectomy within the time they would be enrolled in the trial. Prior tonsillectomy is acceptable (if greater than 6 months prior to screening). 22. Subject 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 subject’s ability to participate in the trial. 23. Subject is judged by the investigator or the medical monitor to be inappropriate for the trial. 24. Subjects receiving any of the prohibited medications within the specified periods or who would be likely to require prohibited concomitant therapy during the trial.