A Project for Two Multicentre, Prospective Open Label Randomized Clinical Studies to Evaluate the Effect of Targeted Therapy Based on Kidney Biopsy Findings in IgAN Patients (CLIgAN)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione Schena Centro Europeo Della Ricerca Sulle Malattie Renali

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Decision date (initial)

2024-10-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Italian Ministry of University (PON RI No. ARS01_00876)

External identifiers

EU CT number

2024-517861-18-00

EudraCT number

2021-006854-29

ClinicalTrials.gov

NCT04662723

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

• To evaluate the therapeutic effect on proteinuria with early corticosteroid therapy, administered after the kidney biopsy in IgAN patients with active renal lesions (ACIgAN) versus standard care of RASBs alone followed by corticosteroids combined with RASBs;
• To evaluate the therapeutic effect of SGLT2i (Dapagliflozin) combined with RASBs on proteinuria versus corticosteroids combined with RASBs in patients with chronic or moderate renal lesions (CHRONIgAN); thus, to avoid the potential side effects of corticosteroid therapy.

Secondary objectives 1

1. • the effect of study treatments on the renal function and on the progression of the kidney damage in IgAN patients at 3 years • after the prediction of ESKD through our IgAN CDSS tool (DialCheck) at the time of the kidney biopsy, to determine whether personalized therapy delays the impairment of the renal function.

Conditions and MedDRA coding

Idiopathic IgA nephropathy (IgAN)

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. ACIgAN study 1. Males and females aged 18 to 75 years. 2. Written informed consent form. 3. Biopsy-proven idiopathic IgAN with active (E1 and/or C1) within 2 weeks. 4. eGFR >= 30 ml/min/1.73 m2. 5. 24 hour proteinuria >= 0.5 g. 6. Patients on treatment or candidate for the treatment with RASBs (either an ACEi or ARB), as per clinical practice, according to the current KDIGO guidelines. CHRONIgAN study 1. Males and females aged 18 to 75 years. 2. Written informed consent form. 3. Biopsy-proven idiopathic IgAN with chronic (T1,2) or moderate (M0,1, S0,1, E0, T0, C0) renal lesions at high or very high CKD risk within 4 weeks. 4. eGFR >= 30 ml/min/1.73 m2. 5. 24-hour proteinuria >= 0.5 g. 6. Patients on treatment or candidate for the treatment with RASBs (either an ACEi or ARB), as per clinical practice, according to the current KDIGO guidelines.

Exclusion criteria 1

1. 1. Non biopsy-proven IgAN 2. IgAN patients with minimal change disease at kidney biopsy and nephrotic syndrome. 3. IgAN patients with macrohematuria and acute renal failure. 4. IgAN patients with rapidly progressive glomerulonephritis (extracapillary lesions in more than 25 % of glomeruli in the kidney biopsy). 5. Patients with secondary IgAN (lupus nephritis, Schoenlein-Henoch purpura, liver cirrhosis). 6. Patients with superimposed IgAN in a kidney transplant. 7. Patients with other types of glomerular diseases 8. Patients with solitary kidney 9. Patients with end-stage kidney disease 10. Bleeding disorders not responsive to treatment 11. Patients with myocardial infarction or cerebrovascular stroke in the previous six months. 12. Severe liver diseases, infections, malignancies. 13. Uncontrolled diabetes (glycemia > 200 mg/dL and HbA1c > 7.5%). 14. Aseptic necrosis of any bone. 15. Any prior immunosuppressive therapy. 16. Other morbidities that can be exacerbated by corticosteroids. 17. Previous adverse side effects and/or contraindications to RASBs and SGLT2is. 18. Pregnancy and breastfeeding. 19. If women of childbearing potential (WOCBP): patients not available to use highly effective contraceptive measures during the study treatment period and up to one month after the last dose of study drugs.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Between-arms difference in proteinuria reduction within 4 months and in nonresponders within 8 months in ACIgAN study.
2. Between-arms difference in proteinuria reduction within 10 months in CHRONIgAN study.

Secondary endpoints 10

1. eGFR slope calculated as mean of individual slope obtained from individual linear regression of eGFR overtime (3 years);
2. eGFR decline > 40 % from the baseline value;
3. composite end point: GFR decline > 40%, ESKD (defined as long-term GFR <= 15 ml/min/1.73m2 for more than three months or need for maintenance dialysis or kidney transplantation) or death due to kidney disease;
4. absolute difference between last GFR value and baseline GFR;
5. stable renal function defined as a decline in GFR <= 5 ml/min/1.73m2 at the end of three years follow- up
6. mean annual change in the slope of the reciprocal of serum creatinine concentration;
7. time-averaged proteinuria (TA-P) calculated as the weighted mean of all postrandomisation measurement, with weights representing the time elapsed since the previous measurement;
8. proteinuria slope, calculated as a mean of individual slope, obtained from individual linear regression of daily proteinuria overtime (3 years);
9. complete remission of proteinuria defined as achievement of urinary protein level <= 0.2 g/day or a urinary protein-to-creatinine ratio <= 0.2 g/g;
10. partial remission of proteinuria defined as achievement of a urinary protein reduction >= 50% or greater compared with the baseline value.

Investigational products

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

Test 3

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione Schena Centro Europeo Della Ricerca Sulle Malattie Renali

Sponsor organisation

Fondazione Schena Centro Europeo Della Ricerca Sulle Malattie Renali

Address

Via Delle Murge 59a

City

Bari

Postcode

70124

Country

Italy

Scientific contact point

Organisation

Fondazione Schena Centro Europeo Della Ricerca Sulle Malattie Renali

Contact name

Francesco Paolo Schena

Public contact point

Organisation

Fondazione Schena Centro Europeo Della Ricerca Sulle Malattie Renali

Contact name

Francesco Paolo Schena

Third parties 1

Locations

1 EU/EEA country · 51 investigational sites

By country

Investigational sites

Results and documents

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

Documents 10 files

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

Application history

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