Date

2025-07-25

Protocol

Protocol changed

Item Changed

Exclusion criteria

Previous Version

1. Participation in the Phase 2b (Parts A and B) study or any previous treatment with atacicept. 2. IgAN secondary to another condition (e.g., liver cirrhosis), or other causes of mesangial IgA deposition including IgA vasculitis (i.e., Henoch-Schonlein purpura), systemic lupus erythematosus (SLE), dermatitis herpetiformis, ankylosing spondylitis 3. Evidence of rapidly progressive glomerulonephritis (loss of ? 50% of eGFR within 3 months of screening) 4. Total urine protein excretion ?5g per 24-hour or urine protein to creatinine ratio (UPCR) ?5 mg/mg based on a 24-hour urine sample during the Screening Period 5. Evidence of nephrotic syndrome within 6 months of screening (serum albumin 3.5 mg/mg) 6. Renal or other organ transplantation prior to, or expected during, the study, with the exception of corneal transplants 7. Concomitant chronic renal disease in addition to IgAN (e.g., diabetic nephropathy, primary focal segmental glomerulosclerosis (FSGS), membranous nephropathy, C3 glomerulopathy, lupus nephritis) 8. Uncontrolled diabetes, defined as hemoglobin-A1c (HbA1c) >7.5% at screening 9. History of tuberculosis (TB), untreated latent TB infection (LTBI), or evidence of active TB determined by a positive Quantiferon test at the Screening Visit.

Next Version

Subjects are not eligible for this study if they fulfill any of the following exclusion criteria at the Screening Visit or during the Screening Period: 1. IgAN secondary to another condition (e.g., liver cirrhosis), or other causes of mesangial IgA deposition including IgA vasculitis (i.e., Henoch-Schonlein purpura), SLE, dermatitis herpetiformis, ankylosing spondylitis 2. Evidence of rapidly progressive glomerulonephritis (loss of ? 50% of eGFR within 3 months of screening 3. Evidence of nephrotic syndrome within 6 months of screening (serum albumin < 30g/L in association with UPCR >3.5 mg/mg 4. Total urine protein excretion ? 5g per 24-hour or urine protein to creatinine ratio (UPCR) ? 5 mg/mg based on a 24-hour urine sample during the Screening Period 5. Renal or other organ transplantation prior to, or expected during, the study with the exception of corneal transplants 6. Concomitant chronic renal disease in addition to IgAN (e.g., diabetic nephropathy, primary focal segmental glomerulosclerosis (FSGS), membranous nephropathy, C3 glomerulopathy, lupus nephritis) 7. Uncontrolled diabetes, defined as hemoglobin-A1c (HbA1c) >7.5% at screening 8. History of tuberculosis (TB), untreated latent TB infection (LTBI), or evidence of active TB determined by a positive Quantiferon test at the Screening Visit. If the subject is undergoing current treatment for LTBI, they must have received at least 4 continuous weeks of an appropriate LTBI treatment prior to the Screening Visit without evidence of re-exposure to be eligible for this study. If on LTBI treatment at the Screening Visit, the subject will be expected to complete an appropriate LTBI treatment regimen to remain in the trial. • Subjects with current household contacts with active TB will be excluded unless prophylaxis treatment has been completed, and evidence that household contacts have completed treatment is provided. • Indeterminate Quantiferon tests may be repeated once by the same test and will be considered positive if retest results are positive or indeterminate. 9. Prohibited medications: • Use of systemic corticosteroids or immunosuppressive medications (e.g., MMF, azathioprine, cyclophosphamide, hydroxychloroquine) for the treatment of IgAN within 3 months prior to screening or expected use during the study. – For glucocorticosteroids (GCS), “Systemic” is defined as oral, rectal or injectable (intravenous or intramuscular) routes of administration. Other routes of administration are allowed, including intra-articular, inhaled, topical, ophthalmic, otic and intranasal. • For non-IgAN indications (e.g., gout flare, exacerbation of asthma, severe rash, etc): – Within 3 months prior to randomization: Use of systemic corticosteroids or immunosuppressive medications for > 1 week or 0.5 mg/kg/day prednisolone or equivalent • Use of B-cell–directed biologic therapies including blisibimod, belimumab, rituximab, ocrelizumab for any period of time • Use of other biologics (e.g., anti-TNF, abatacept, anti-IL-6) and investigational biologics 10. Clinically significant or predefined abnormalities per central laboratory tests, at the Screening Visit, meeting any of the criteria below: • serum IgG below 7 g/L • aspartate aminotransferase, alanine aminotransferase or alkaline phosphatase level > 2.5 × upper limit of normal (ULN) or total bilirubin >1.5 × ULN. i. If subject has a known history of Gilberts (history of isolated increase in total bilirubin without increase in liver transaminases), contact the Medical Monitor for further discussion. • For The Czech Republic only, the following criteria also apply: i. hemoglobin <10 g/100 mL in men and hemoglobin <9 g/100 mL in women ii. platelets <100,000/mm3 11. Administration of a live and live-attenuated vaccinations within 30 days prior to randomization 12. History or current diagnosis of any demyelinating disease such as, but not restricted to, multiple sclerosis (MS) or optic neuritis (ON) 13. Patients with history of unstable angina, Class III and IV congestive heart failure and/or clinically significant arrhythmia, as judged by the Investigator. 14. Any condition, including any uncontrolled disease state other than IgAN, that in the opinion of the Investigator or the Sponsor/designee constitutes an inappropriate risk or a contraindication for participation in the study or that could interfere with the study objectives, conduct or evaluation 15. Active clinically significant viral, bacterial or fungal infection, or any major episode of infection requiring hospitalization or treatment with parenteral anti-infectives within 4 weeks prior to, or during the Screening Visit, or completion of oral anti-infectives within 2 weeks prior to, or during the Screening Visit or a history of recurrent infections (i.e., 3 or more of the same type of infection in a 12-month rolling period). Vaginal candidiasis, onychomycosis and genital or oral herpes simplex virus considered by the Investigator to be sufficiently controlled are not exclusionary. • For Germany only, the following criteria also apply: Specifically for COVID-19: Evidence of positive test for SARS-CoV-2, by PCR, at the Screening Visit; Subjects with a previous COVID-19 infection may be included provided the PCR test is negative for SARS-CoV-2 and they do not have chronic symptoms as a result of COVID-19. COVID-19 testing may be performed at local lab, per site/local guidelines. 16. History of acute or chronic infection with human immunodeficiency virus or hepatitis B virus. • Positive hepatitis B surface antigen (HBsAg)Subjects who are HBsAg negative and hepatitis B core antibody (HBcAb) positive with no detectable hepatitis B virus (HBV) DNA are eligible but will require monthly HBV DNA monitoring through safety follow up 17. History of splenectomy 18. History of malignancy (hematologic or solid tumor) within 5 years prior to Screening Visit, except adequately treated basal cell or squamous cell carcinomas of the skin (no more than 3 lesions requiring treatment in lifetime) or carcinoma in situ/cervical intraepithelial neoplasia of the uterine cervix • For Germany only the following criteria also apply: History of malignancy within the past 5 years prior to Screening (except for adequately treated basal cell carcinoma or non-metastatic squamous cell carcinoma of the skin or cervical carcinoma in situ, with no evidence of recurrence). 19. Known hypersensitivity to atacicept or any component of the formulated atacicept 20. Major surgery within 6 weeks prior to the Screening Visit or planned/expected major surgery during the study period (including the Safety FU Period) • Major surgery often involves opening one of the major body cavities (abdomen, chest, and skull) and/or use of general anesthesia. Types of surgery that have the highest risk include heart or lung, liver, abdomen, or major operations on the bones and joints (for example, hip replacement) 21. Clinically significant history of alcohol or drug abuse in the 1 year prior to the Screening Visit as per Investigator opinion 22. Unwillingness or lack of capacity to follow all study procedures 23. Treatment with other investigational agents within the last 4 weeks or 5 half-lives, whichever is longer, prior to the Screening Visit