A PILOT PROOF-OF–CONCEPT STUDY TO ASSESS THE EFFICACY AND SAFETY OF A 6 MONTHS RAVULIZUMAB TREATMENT IN PATIENTS WITH FLARES OF CORTICOSTEROID-RESISTANT IDIOPATHIC IgA NEPHROPATHY

Prior treatment

• Concomitant significant renal disease other than IgA nephropathy (eg, SLE, cirrhosis, celiac disease)
• Patients who have received any investigational agent within the last 30 days or are in follow-up of another clinical study prior to study enrolment
• History of meningococcal infection within 12 months before Screening
• Known contraindication to either of the meningococcal (group ACWY conjugate and group B vaccines), Haemophilus influenzae type b (Hib) and Streptococcus pneumonia vaccines used in this study. Refer to the most recent local product information for each vaccine for the current list of contraindications
• Receipt of an organ transplant (including hematologic transplant) planned or transplant during the Treatment Period
• Patients with systemic bacterial or fungal infections, as demonstrated by a positive culture result, that require systemic treatment with antibiotics or antifungals. Patients receiving empiric or prophylactic antibiotics are not excluded

Other illness

• Active psychiatric disorder, including, but not limited to schizophrenia, bipolar disorder, or severe depression requiring current pharmacological intervention
• Known medical history or evidence of chronic liver disease or cirrhosis
• Known human immunodeficiency virus (HIV) infection; hepatitis C virus (HCV) infection or hepatitis B virus infection
• Other medical conditions or comorbidities which, in the opinion of the Investigator, would interfere with study compliance or data interpretation
• Secondary aetiologies of IgA nephropathy (e.g., inflammatory bowel disease, celiac disease)
• Malignancy (except for non-melanoma skin cancers, cervical in-situ carcinoma, breast ductal carcinoma in situ, or stage 1 prostate cancer) within the last 5 years

Lab values

• Estimated GFR <30 mL/min/1.73 m2 during Screening calculated by CKD-EPI
• Clinical laboratory test results considered clinically relevant and unacceptable in the opinion of the Investigator

Other

• Patients who consume more than 14 units of alcohol a week (unit 1 glass of wine [125 mL] = 1 measure of spirits = ½ pint of beer)
• Pregnant, breastfeeding, or intending to conceive during the course of the study
• Sustained Blood pressure > 140 / 90 mmHg as defined by 2 or more readings >30 min apart during the run-in period, as measured in supine position after 10 minutes of rest
• Diagnosis of Henoch-Schonlein Purpura (IgA Vasculitis)

• Participant must be ≥ 18 years of age at the time of signing the informed Consent and capable of giving informed consent
• Written consent
• Previous biopsy proven idiopathic IgAN
• Persistent activity despite adequate standard of care treatment: a. Patients with preserved renal function: Ratio proteinuria/creatinine >1 g/g associated to haematuria > 15 cells/microliter after 6 months of treatment with corticosteroids according to the recommendations of the guidelines. b. Patients with AKI (acute kidney injury): persistence of haematuria and proteinuria and absence of improvement of renal function 4 weeks after the onset of the outbreak and treatment with 3 corticosteroid pulses of at least 250 mg followed by 1 mg/Kg/day oral prednisone Patients with evidence of extracapillary proliferation could be considered candidates for treatment with ravulizumab after treatment with the standard of care for this condition with 3 pulses of 6- methylprednisolone and at least 1 pulse of cyclophosphamide.
• Evidence of mesangial deposition of C5b-9 with or without capillary deposits of C3d
• Vaccination against meningococcus, haemophilus and pneumococcus
• Participants on SGLT-2 inhibitors (eg, empagliflozin) must be on a stable dose for ≥3 months prior to Screening with no planned change in dose during the study.
• Compliance with stable and optimal dose of RAS inhibitor treatment including maximum allowed or tolerated ACE inhibitor and/or angiotensin receptor blocker dose for ≥3 months prior to Screening with no expected change in dose during the study.
• Absence of specific contraindications for ravulizumab treatment.
• Female participants of childbearing potential, and male participants with female partners of childbearing potential must follow protocol specified contraception guidance as described in Appendix 4.