Date

2024-12-16

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

• 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.