Phase 3 open study of RE-021 in patients with IgA nephropathy

JRCT ID: jRCT2051240070

Registered date:21/06/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: IgA nephropathy
• Date of first enrollment: 16/07/2024
• Target sample size: 30
• Study type: Interventional
• Intervention(s): The sutudy drug will be administered orally at 200mg once a day, then increased to 400mg once a day. Dosing period should be 110 weeks.

Outcome(s)

• Primary Outcome: Change from baseline in urinary protein-to-creatinine ratio (UP/C) based on 24 hour urine samples at 36 weeks

Secondary Outcome

1. Estimated percentage change in glomerular filtration rate (eGFR) 52 weeks after the onset of the acute effect (Acute response is defined as the period from the start of study drug to Week 6, and data from Week 6 to Week 58 will be analyzed.; eGFR Chronic slope at 1 year)
2. Estimated percentage change in glomerular filtration rate (eGFR) 104 weeks after the onset of the acute effect (Acute response is defined as the period from the start of study drug to Week 6, and data from Week 6 to Week 110 will be analyzed.; eGFR Chronic slope at 2 years)
3. Estimated glomerular filtration (eGFR) rate at Week 110 Change (Analyze data from Day 1 through Week 110; eGFR total slope at 2 years)
4. Temporal change from baseline in Estimated glomerular filtration rate (eGFR) up to 110 weeks and proteinuria variables based on 24 h urine samples [e.g., urinary protein excretion, urinary albumin excretion, urinary albumin-to-creatinine ratio (UA/C), and UP/C]
5. Proportion of patients with documented 40% decline in eGFR, ESRD, or death [ESRD is defined as initiation of renal replacement therapy (RRT: chronic dialysis or renal transplantation) or persistence of eGFR < 15 mL/min/1.73 m2]

Key inclusion & exclusion criteria

• Age minimum: >= 10age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Patients who meet all of the following criteria will be included.
1. Outpatients aged 10 years or older at the time of signing the ICF
2. Patients diagnosed with primary IgA nephropathy by renal biopsy performed in the past
3. Patients with urinary protein >= 0.5 g/day at screening
4. Patients with eGFR >= 30 mL/min/1.73 m2 at screening
5. Patients receiving an SGLT2 inhibitor who have been receiving the same SGLT2 inhibitor continuously for at least 24 weeks before the screening test and at a constant dose for 12 weeks before screening
6. Patients who consent to contraception
7. Patients who can sign the ICF as described in the section on procedures for obtaining consent, including compliance with the requirements and restrictions described in the ICF and the protocol. (In the case of minors, signatures by Ascent and Substitute).
8. Patient using Angiotensin-converting enzyme inhibition at the same dosage and administration (maximum tolerated capacity and >= 1/2 of the maximum approved dose) for at least 12 weeks before the screening test (ACEI) and/or angiotensin n-receptor blockers (ARBs).

Exclude criteria

Patients should be excluded from the study if any of the following criteria are met
1. Patients with IgA nephropathy due to other diseases (Systemic lupus erythematosus, cirrhosis, etc.) or IgA vasculitis (Henoch-Schonlein purpura)
2. Patients who underwent palatine tonsillectomy within 2 years before screening. Patients who plan to undergo palatine tonsillectomy during the study period.
3. Patients with more than 25% of the glomeruli identified as cellular glomerular crescents if a renal biopsy was performed within 6 months before the screening test.
4. Patients with IgA nephropathy plus other chronic kidney diseases, such as diabetic nephropathy.
5. Patients with a history of organ transplantation, excluding corneal transplantation
6. Patients who need to continue concomitant prohibited drugs
7. Clinically significant cerebrovascular disease (transient ischemic attack or stroke) and/or coronary artery disease (myocardial infarction or Hospitalization for unstable angina, new onset of angina with a positive functional test, coronary angiographic evidence of stenosis, or need for coronary revascularization)
8. Diagnosis of jaundice, hepatitis, or other hepatobiliary disease or liver function tests at screening [alanine aminotransferase (ALT) or aspartate aminotransferase (AST)] > 2 times the upper limit of normal
9. Patients diagnosed with malignancy within 2 years prior to consent (Excludes appropriately treated basal cell carcinoma, squamous skin carcinoma, and cervical carcinoma)
10. Patients with any of the following laboratory values at the time of the screening test
1) Hematocrit < 27% (0.27 v/v)
2) Hemoglobin < 9 g/dl (90 g/L)
3) Potassium > 5.5 mEq/L
11. Patients with or a history of alcohol, drug abuse, or drug dependence
12. Patients with a history of serious adverse reactions or allergic reactions or hypersensitivity to sparsentan, angiotensin n-receptor blockers, or endothelin-receptor blockers
13. Pregnant women, patients who may be pregnant, patients who are breastfeeding, and patients who wish to become pregnant during the study
14. Patients who participated in another study within 28 days before the screening test
15. Patients with a positive human immunodeficiency virus (HIV) antibody test at screening
16. Patients with a positive hepatitis B virus surface antigen (HBsAg), hepatitis B virus surface antibody (HBsAb), or hepatitis B virus core antibody (HBcAb) test at screening. However, patients with a single positive HBs antibody due to HB vaccination can be enrolled.
17. Patients with a positive hepatitis C virus (HCV) antibody test at screening. However, if the HCV antibody test is positive, an RNA test is performed, and if the result is negative, enrollment is allowed.
18. Patients who donated 400 mL within 12 weeks or >= 200 mL within 4 weeks prior to obtaining consent (Contains platelets and plasma components) or who donated blood from screening to the day before the start of treatment (Day -1)
19. Other patients for whom participation in the study was deemed inappropriate by the investigator (sub investigator)

Related Information

• Primary Sponsor: Nakamura Yoshihide