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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institut De Recerca Biomedica De Lleida Fundacio Dr. Pifarre, Institut De Recerca Biomedica De Lleida Fundacio Dr. Pifarre

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13]

Trial duration

26 May 2023 → ongoing

Decision date (initial)

2024-06-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-512154-24-00

EudraCT number

2021-005609-28

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To determine the quantitative reduction of proteinuria and haematuria in adult participants with IgAN.

Secondary objectives 3

1. To evaluate the efficacy of ravulizumab on measures of kidney function in adult participants with IgAN.
2. To evaluate the efficacy of ravulizumab to improve measures of kidney function in adult participants with IgAN.
3. To characterize the safety and tolerability of ravulizumab in adult participants with IgAN

Conditions and MedDRA coding

IgA nephropathy

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Participant must be ≥ 18 years of age at the time of signing the informed Consent and capable of giving informed consent
2. Previous biopsy proven idiopathic IgAN
3. 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.
4. Evidence of mesangial deposition of C5b-9 with or without capillary deposits of C3d
5. Vaccination against meningococcus, haemophilus and pneumococcus
6. 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.
7. 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.
8. Absence of specific contraindications for ravulizumab treatment.
9. 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.
10. Written consent

Exclusion criteria 18

1. Concomitant significant renal disease other than IgA nephropathy (eg, SLE, cirrhosis, celiac disease)
2. 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
3. Estimated GFR <30 mL/min/1.73 m2 during Screening calculated by CKD-EPI
4. Secondary aetiologies of IgA nephropathy (e.g., inflammatory bowel disease, celiac disease)
5. Diagnosis of Henoch-Schonlein Purpura (IgA Vasculitis)
6. Receipt of an organ transplant (including hematologic transplant) planned or transplant during the Treatment Period
7. Clinical laboratory test results considered clinically relevant and unacceptable in the opinion of the Investigator
8. 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
9. 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
10. 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
11. Active psychiatric disorder, including, but not limited to schizophrenia, bipolar disorder, or severe depression requiring current pharmacological intervention
12. History of meningococcal infection within 12 months before Screening
13. 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
14. Known medical history or evidence of chronic liver disease or cirrhosis
15. Known human immunodeficiency virus (HIV) infection; hepatitis C virus (HCV) infection or hepatitis B virus infection
16. Other medical conditions or comorbidities which, in the opinion of the Investigator, would interfere with study compliance or data interpretation
17. 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)
18. Pregnant, breastfeeding, or intending to conceive during the course of the study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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)

Secondary endpoints 6

1. Percentage of participants achieving complete remission 26 weeks after treatment with ravulizumab
2. Evolution of proteinuria and haematuria (based on 24- hr urine collection(s)) after treatment withdrawal (from Week 26 to Week 46)
3. To measure the evolution of serum creatinine levels (quantitative) from baseline to Week 46
4. To measure the evolution of urine C5b-9 levels (quantitative) from baseline to Week 46
5. To measure the slope of eGFR computed from baseline to Week 46
6. Proportion of patients discontinuing treatment with ravulizumab due to adverse effects associated with the drug

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institut De Recerca Biomedica De Lleida Fundacio Dr. Pifarre

Sponsor organisation

Institut De Recerca Biomedica De Lleida Fundacio Dr. Pifarre

Address

Avinguda De L'Alcalde Rovira Roure 80

City

Lleida

Postcode

25196

Country

Spain

Scientific contact point

Organisation

Institut De Recerca Biomedica De Lleida Fundacio Dr. Pifarre

Contact name

Diego Arango Del Corro

Public contact point

Organisation

Institut De Recerca Biomedica De Lleida Fundacio Dr. Pifarre

Contact name

Diego Arango Del Corro

Institut De Recerca Biomedica De Lleida Fundacio Dr. Pifarre

Sponsor organisation

Institut De Recerca Biomedica De Lleida Fundacio Dr. Pifarre

Address

Avinguda De L'Alcalde Rovira Roure 80

City

Lleida

Postcode

25196

Country

Spain

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications