A Multicenter, Interventional Treatment, Open-Label Study to Evaluate the Efficacy and Safety of 16 mg of VR-205 in Primary IgA Nephropathy Patients at Risk of Developing End-Stage Renal Disease (ESRD)
A Study to Evaluate the Efficacy and Safety of VR-205 in Primary IgA Nephropathy Patients at Risk of Developing End-Stage Renal Disease (ESRD)
Itoigawa Suguru
Syneos Health Clinical K.K.
27F Shinagawa Season Terrace, 1-2-70 Konan, Minato-ku, Tokyo
+81-80-9123-8285
VR-205A-01-CAZ-3001@syneoshealth.com
Itoigawa Suguru
Syneos Health Clinical K.K.
27F Shinagawa Season Terrace, 1-2-70 Konan, Minato-ku, Tokyo
+81-80-9123-8285
VR-205A-01-CAZ-3001@syneoshealth.com
Recruiting
April. 26, 2024
June. 10, 2024
36
Interventional
single arm study
open(masking not used)
uncontrolled control
single assignment
treatment purpose
Participants must meet all of the following inclusion criteria to be eligible for enrollment into the study:
1. Japanese male or female aged >=18 years at the initiation of the screening period (Visit 1).
2. Diagnosis of primary IgAN verified by biopsy within 10 years prior to screening.
3. On a stable dose of RAS inhibitor therapy (ACEIs and/or ARBs) at the maximum allowed or the maximum tolerated dose according to the 2021 Kidney Disease Improving Global Outcomes (KDIGO) guidelines for at least 3 months prior to inclusion. Patients should remain on their regimen of RAS inhibitor(s) for the entire duration of the study.
4. Patients who are SGLT-2 inhibitor therapy must be on a stable dose of SGLT-2 inhibitor for the 6 months prior to inclusion.
5. Participants who are administering mineralocorticoid receptor inhibitors, MRAs (mineralocorticoid receptor antagonists) or MRBs (mineralocorticoid receptor blockers), or fish oil, should be on a stable dose of these drugs for the 3 months prior to inclusion.
6. eGFR >=35 mL/min per 1.73 m2 and <=90 mL/min per 1.73 m2 (using the CKD-EPIcr formula, adapted to Japanese population)
7. Proteinuria of >=1 g/day or urine protein creatinine ratio (UPCR) of >=0.8 mg/g CR (>=90 mg/mmol) demonstrated in 2 consecutive measurements based on 24-hour urine sampling and separated by at least 2 weeks and calculated by the central laboratory (baseline values will be defined as the geometric means of the 2 measurements for both proteinuria and UPCR).
8. Female participants of childbearing potential must agree to use adequate contraception.
9. Participants who provided written informed consent.
10. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
Participant candidates must not be enrolled in the study if they meet any of the following criteria:
1. Participants with known hypersensitivity to glucocorticoids (GCS) or any of the ingredients of VR-205
2. Participants who have undergone kidney transplant, have liver cirrhosis, have poorly controlled type 1 or 2 diabetes mellitus [HbA1c >8% (or 64 mmol/mol)], have a history of unstable angina pectoris, have class III or IV congestive heart failure, have clinically significant cardiac arrhythmia, have osteoporosis in medium- or high- risk category according to Osteoporosis Self-Assessment Tool for Asians (OSTA) guidelines, have known glaucoma, have known cataract(s) and/or a history of cataract surgery (unless surgery was performed on both eyes), have been treated with systemic immunosuppressive medication other than GCS within 12 months prior to enrollment, are taking potent inhibitors of cytochrome P450 3A4 (CYP3A4).
3. Participants with secondary IgAN or other forms of glomerulopathies.
4. Patients with nephrotic syndrome (i.e., proteinuria >3.5 g/day and with serum albumin <3.0 g/dL, with or without edema).
5. Participants with a history or the presence of clinically significant cardiac, hepatic, renal, respiratory, endocrinological, neurological, or hematological disease.
6. Patients with acute, chronic, or latent infectious disease including hepatitis, tuberculosis (TB), human immunodeficiency virus (HIV), and chronic urinary tract infections;
7. Participants with unacceptable blood pressure control defined as a blood pressure consistently above national guidelines for proteinuric renal disease, as assessed by the Investigator. Patients with >=140 mmHg systolic blood pressure or >=90 mmHg diastolic blood pressure are not eligible.
8. Participants with planned tonsillectomy during the duration of the trial or with recent tonsillectomy during the last 6 months prior to inclusion.
9. Female participants who are pregnant or breast-feeding, or who are suspected to be pregnant, or planning to become pregnant.
10. Females who are sexually active and do not use medically acceptable forms of contraception.
11. Participants who have any clinically significant abnormalities on the pre-study physical examination, electrocardiogram (ECG), laboratory tests, or urine drug screen.
12. Participants who have been treated with any systemic GCS within 6 months before enrollment for IgAN indication.
13. Participants who have been treated with any systemic GCSs within 12 months before enrollment except for a maximum of 3 periods of 2 weeks with an equivalent of 0.5 mg/kg/day prednisolone or less for non-IgAN indications. However, no systemic GCS allowed 3 months before enrollment.
14. Participants with a history of malignant tumor within 2 years, except for basal cell or squamous cell skin cancer.
15. Participants on treatment with endothelin receptor antagonists or any other potential new therapy for IgAN.
16. Participants who plan to receive prohibited concomitant drugs/procedures.
17. Participation in any other clinical trials within 3 months before the initiation of the screening period or wish to participate in other clinical studies during this study.
18. Investigator site staff or Viatris employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, or their respective family members.
19. Participants who have any serious acute/chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk of study participation, affect the interpretation of the study results, or, in the investigator's judgment, make the participant inappropriate for the study.
18age old over
No limit
Both
Primary IgA Nephropathy
VR-205, 16 mg (four capsules QD) will be administered orally for 9 months during the treatment period.
After completing 9 months of study drug treatment, the daily dose of the study drug will be reduced from 4 capsules (VR-205, 16 mg) to 2 capsules (VR-205, 8 mg) for 2 weeks to prevent insufficiency of the adrenal glands (tapering period).
Geometric mean UPCR (Urine protein to creatinine ratio: UPCR is based on 24-hour urine collection) at 9 months over baseline value
