Study to assess whether the drug Ravulizumab works in patients with kidney problems due to IgA immunoglobulin and who do not respond to corticosteroids

Phase 1

• Conditions: Treatment for IgA nephropathy flares; Therapeutic area: Body processes [G] - Immune system processes [G12]

• Registration Number: EUCTR2021-005609-28-ES
• Lead Sponsor: Dr. Alfons Segarra Medrano

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2022-01-03
• Last Update Posted: 28 March 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 1

Inclusion Criteria

1. Persistent activity despite adequate standard of care treatment
1a. 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.
1b. 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 corticoesteroid 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- mehtylprednisolone and at least 1 pulse of
cyclophosphamide.
2. Evidence of mesangial deposition of C5b-9with or without capillary
deposits of C3d.
3. Increased urinary levels of C5b-9. The reference values for urine C5b-9
excretion have been obtained from a control group of healthy people
4. Vaccination against meningococcus, haemophilus and pneumococcus
5. Absence of specific contraindications for ravulizumab treatment.
6. Written consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 15
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Concomitant significant renal disease other than IgA nephropathy.
2. Sustained Blood pressure > 140 / 90 mmHg as defined by 2 or more readings during the run in period, as measured in supine position after 10 minutes of rest.
3. Secondary aetiologies of IgA nephropathy (e.g. inflammatory bowel disease, celiac disease).
4. Diagnosis of Henoch-Schonlein Purpura (IgA Vasculitis).
5. Receipt of an organ transplant (including hematologic transplant).
6. Clinical laboratory test results considered clinically relevant and unacceptable in the opinion of the Investigator.
7. 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.
8. 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.
9. 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.
10. Active psychiatric disorder, including, but not limited to schizophrenia, bipolar disorder, or severe depression requiring current pharmacological intervention.
11. History of meningococcal infection within 12 months before Screening.
12. Known contraindication to either of the meningococcal vaccines (group ACWY conjugate and group B vaccines) used in this study. Refer to the most recent local product information for each vaccine for the current list of contraindications.
13. Known medical history or evidence of chronic liver disease or cirrhosis.
14. Known human immunodeficiency virus (HIV) infection; hepatitis C virus (HCV) infection or hepatitis B virus infection.
15. Other medical conditions or comorbidities which, in the opinion of the Investigator, would interfere with study compliance or data interpretation.
16. 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).
17. Pregnancy

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective is to determine the quantitative reduction of proteinuria and haematuria 26 weeks after starting treatment with ravulizumab;Secondary Objective: 1.- To determine the number (%) of patients achieving complete remission defined by<br>UPCR < 0,3 g/g, number of red blood cells < 5 microliter and improvement of serum<br>creatinine to achieve baseline levels (only for patients with AKI) 26 weeks after treatment with ravulizumab.<br>2. - To measure the evolution of serum creatinine (quantitative) at 26 weeks.<br>3. - To measure the evolution of urine C5b-9 levels (quantitative) at 26 weeks.<br>4. - To determine the evolution of haematuria and proteinuria 20 weeks after treatment<br>withdrawal (at week 46);Primary end point(s): The primary endpoint is the quantitative reduction of proteinuria and hematuria 26<br>weeks after starting treatment with ravulizumab;Timepoint(s) of evaluation of this end point: 6 month after the treatment

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 6 month after the treatment;Timepoint(s) of evaluation of this end point: - Renal function (serum creatinine and glomerular filtration estimated by CKD-EPI formula), complete and biochemical hemogram with liver profile, 24h urine profile<br>to assess the presence of proteinuria, urinary sediment and fundamental<br>electrolytes (every 15 days the first 3 months and then quarterly).<br>- Proportion of patients discontinuing treatment with ravulizumab due to adverse<br>effects associated with the drug.