Ravulizumab for IgA nephropathy | Idiopathic IgA nephropathy

Inclusion criteria

• {"criterion_text":"- Participant must be ≥ 18 years of age at the time of signing the informed Consent and capable of giving informed consent\n- Written consent\n- Previous biopsy proven idiopathic IgAN\n- 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.\n- Evidence of mesangial deposition of C5b-9 with or without capillary deposits of C3d\n- Vaccination against meningococcus, haemophilus and pneumococcus\n- 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.\n- 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.\n- Absence of specific contraindications for ravulizumab treatment.\n- 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."}

Exclusion criteria

• {"criterion_text":"- Concomitant significant renal disease other than IgA nephropathy (eg, SLE, cirrhosis, celiac disease)\n- 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\n- Active psychiatric disorder, including, but not limited to schizophrenia, bipolar disorder, or severe depression requiring current pharmacological intervention\n- History of meningococcal infection within 12 months before Screening\n- 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\n- Known medical history or evidence of chronic liver disease or cirrhosis\n- Known human immunodeficiency virus (HIV) infection; hepatitis C virus (HCV) infection or hepatitis B virus infection\n- Other medical conditions or comorbidities which, in the opinion of the Investigator, would interfere with study compliance or data interpretation\n- 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)\n- Pregnant, breastfeeding, or intending to conceive during the course of the study\n- 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\n- Estimated GFR <30 mL/min/1.73 m2 during Screening calculated by CKD-EPI\n- Secondary aetiologies of IgA nephropathy (e.g., inflammatory bowel disease, celiac disease)\n- Diagnosis of Henoch-Schonlein Purpura (IgA Vasculitis)\n- Receipt of an organ transplant (including hematologic transplant) planned or transplant during the Treatment Period\n- Clinical laboratory test results considered clinically relevant and unacceptable in the opinion of the Investigator\n- 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\n- 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"}

Primary endpoints

• {"endpoint_text":"- Quantitative reduction of proteinuria and haematuria (based on 24-hr urine collection(s)) from baseline to Week 26 (6 months after starting treatment with ravulizumab)","definition_or_measurement_approach":"Quantitative reduction based on 24-hour urine collection(s) from baseline to Week 26 (6 months after starting treatment)."}

Secondary endpoints

• {"endpoint_text":"- Percentage of participants achieving complete remission 26 weeks after treatment with ravulizumab","definition_or_measurement_approach":"Proportion/percentage of participants meeting protocol definition of complete remission at 26 weeks."}
• {"endpoint_text":"- Evolution of proteinuria and haematuria (based on 24- hr urine collection(s)) after treatment withdrawal (from Week 26 to Week 46)","definition_or_measurement_approach":"Change over time in proteinuria and haematuria measured by 24-hour urine collections between Week 26 and Week 46."}
• {"endpoint_text":"- To measure the evolution of serum creatinine levels (quantitative) from baseline to Week 46","definition_or_measurement_approach":"Quantitative measurement of serum creatinine from baseline to Week 46."}
• {"endpoint_text":"- To measure the evolution of urine C5b-9 levels (quantitative) from baseline to Week 46","definition_or_measurement_approach":"Quantitative measurement of urine C5b-9 levels from baseline to Week 46."}
• {"endpoint_text":"- To measure the slope of eGFR computed from baseline to Week 46","definition_or_measurement_approach":"Computation of eGFR slope from baseline through Week 46."}
• {"endpoint_text":"- Proportion of patients discontinuing treatment with ravulizumab due to adverse effects associated with the drug","definition_or_measurement_approach":"Proportion of patients who discontinue study treatment because of adverse events attributed to ravulizumab."}

Spain

Earliest CTIS Part Ii Submission Date

31-05-2024

Latest Decision Or Authorization Date

28-06-2024

Processing Time Days

28

Number Of Sites

1

Number Of Participants

15

Primary sponsor

Full Name

Institut De Recerca Biomedica De Lleida Fundacio Dr. Pifarre

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

Spain