Immunoglobulin A (IgA) Nephropathy
Conditions
Interventions
In Sri Lanka, this study will be conducted at the following centers
• Sri Jayawardenapura General Hospital
• National Hospital of Sri Lanka.
Randomization will be a stratified randomization. All
Sponsors
Visterra, Inc.
Eligibility
Inclusion criteria
Inclusion criteria: Participants are eligible to be included in the study only if all of the following criteria apply: 1. Participant is a male or female greater than or equal 18 years of age at the time of signing the informed consent. 2. Participant has biopsy-confirmed IgAN. 3. Participant has medical records showing they have been on stable and maximally tolerated doses of either ACEI or ARB, as per SOC and applicable guidelines, for at least 3 months preceding screening. Participants should be on at least 50% of the maximum recommended dose of these agents to be considered as having adequate RAAS blockade. Participants who are unable to tolerate ACEI/ARB therapy may be eligible for participation in the study if their overall management of IgAN, including BP control, is as per SOC and applicable guidelines. 4. Participant has screening uPCR greater than or equal to 0.75 g/g measured from a 24-hour urine (or an intended 24-hour urine sample) or 24-hour urine protein greater than or equal to 1.0 g/d, as measured from 24-hour urine collection (or an intended 24-hour urine sample). The proteinuria should be stable, defined as 25%, a repeat measurement of proteinuria will be done after 15 days and the participant should fulfill the above proteinuria criteria to be eligible for randomization in the study. • The proteinuria should be assessed when the participant is considered to be in a steady state with no recent heavy exercise, fever, or other potential issues that could impact the result. 5. Participant has eGFR greater than or equal to 45 mL/min/1.73 m2, calculated using the CKD-EPI formula. The eGFR should be stable, as defined by a 25%, a repeat measurement of eGFR will be done after 15 days and the participant should fulfill the eGFR criteria to be eligible for randomization in the study. • The eGFR should be measured when the participant is considered to be in a steady state without recent changes in volume status, medications that could impact the result (eg, nonsteroidal anti-inflammatory drugs [NSAIDs], aminoglycosides, co-trimoxazole), or changes in dietary protein intake. 6.Participant’s serum Ig values must meet the following criteria: •IgG: greater than or equal 700 mg/dL •IgM: greater than or equal 40 mg/dL •IgA: greater than or equal 70 mg/dL 7.Female participants of childbearing potential must have a negative serum pregnancy test prior to the first dose. 8.Participant is willing to adhere to contraceptive requirements specified.
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if they meet any of the following criteria: 1.Participant has secondary forms of IgAN as defined by the treating physician (eg,Henoch-Schonlein purpura, minimal change disease with IgA deposits, infection associated IgAN, or IgAN-associated with hepatic cirrhosis). 2.Participant has co-existing CKD, other than IgAN. 3.Participant has evidence of additional pathological findings in the kidney biopsy (eg,diabetic kidney disease, membranous nephropathy, or lupus nephritis). However, hypertensive vascular changes are acceptable. 4.Participant has kidney biopsy MEST or MEST-C score of T2 or C2 from the OxfordIgAN classification schema. If MEST-scoring was not performed, the presence of > 50% tubulo-interstitial fibrosis or crescents in > 25% of glomeruli is exclusionary. 5.Participant has nephrotic syndrome, defined for this purpose as 24-hour urine protein>3.5 g with concurrent hypoalbuminemia (serum albumin 350 mg/dL), and edema. 6.Participant has received a solid organ transplant, including kidney. 7.Participant has received bone marrow or hematologic stem cell transplantation. 8.Participant is currently receiving systemic immunosuppression (excluding topical, ophthalmic, per rectum, or inhaled corticosteroids). 9.Participant has received systemic steroids within the 24 weeks prior to initial screening. 10.Participant has received treatment with 2 or more systemic immunosuppressive agents within 2 years prior to initial screening. 11.Participant has chronic infectious diseases (eg, chronic urinary tract infection; chronicsinusitis; bronchiectasis; active pulmonary or systemic tuberculosis; chronic viralhepatitis, such as hepatitis C or hepatitis B; or human immunodeficiency virus infection). 12. Participant has acute infectious disease at the time of screening. Participants may be re-screened following resolution of acute infection (such as urinary tract infection or respiratory tract infection), provided there is no evidence of an immunosuppressive condition that predisposed the participant to this infection. 13. Participant has Type 1 diabetes. 14. Participant has uncontrolled Type 2 diabetes, as evidenced by a screening hemoglobin A1c value > 8%. 15. Participant has uncontrolled BP (> 140 mm Hg systolic or > 90 mm Hg diastolic), Systolic and diastolic BP should be assessed while the participant is seated or supine for at least 5 minutes in a quiet room without distractions. BP should be measured with a completely automated device. At least 3 readings should be taken and average values from these 3 readings should be calculated. 16. Participant has a history of chronic autoimmune neurodegenerative disorder such as multiple sclerosis. 17. Participant has a known allergy or intolerance to any component of the study intervention. 18. Participant is breastfeeding. 19. Participant has poorly compensated or controlled ischemic heart disease or cardiomyopathy, as judged by the Investigator. 20. Participant has chronic obstructive pulmonary disease (COPD) or asthma that has required systemic steroid therapy during the prior year. If COPD is present, severity must not exceed Global Initiative for Chronic Obstructive Lung Disease 1 (mild), defined as a forced 1-second expiratory volume (FEV1) > 80% of predicted. 21. Participant has known cirrhosis or liver dysfunction, defined as presence of coagulopathy, platelet count < 100,00
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Significant difference among the three groups receiving three doses of the interventional drug on following parameter - Adverse events graded by severity, clinical laboratory tests, vital sign measurements, and physical examinations A complete physical examination, including assessments of the cardiovascular, respiratory, gastrointestinal, and neurological systems will be completed at the screening, Month 12 visit, and Month 16 visits. Vital signs include weight, temperature, pulse rate, respiratory rate, and systolic and diastolic blood pressure which will be taken at each visit (screening visit, month 0-16 visits) Laboratory tests include: •Hepatitis B virus, Hepatitis C virus, HIV serology- at screening visit •Serum beta-human chorionic gonadotropin (females only)- at screening visit •Urine ?- beta-human chorionic gonadotropin (females only)- at month 0 (day 1 prior to IV infusion) and at month 1-12 visits, month 16 •Hemoglobin A1c- at screening visit •Serum chemistry- screening visit, at month 0 (day 1 prior to IV infusion) and at month 1-12 visits, month 16 •Hematology- screening visit, at month 0 (day 1 prior to IV infusion) and at month 1-12 visits, month 16 •Urinalysis (dipstick and microscopy)- screening visit, at month 0 (day 1 prior to IV infusion) and at month 1-12 visits, month 16 •24-hour urine collection- screening visit, month 9,12 & 16 visit •Urine sample for uPCR determination- screening visit, at month 0 (day 1 prior to IV infusion) and at month 1-12 visits, month 16 •Blood sample for lymphocytes- at month 0 (day 1 prior to IV infusion), month 6, 12 & 16 visit •Serum for PK13- month 0 (day 1 pre IV infusion, post IV infusion, day 8, 18, 30) visit, and at month 1-12 visits, month 16 •Blood for total IgA, IgG, and IgM- screening visit, month 0-16 visits •Blood for IgA subtypes- month 0 (day 1 pre IV infusion), month 3,6,9,12,16 visits •Serum for APRIL-month 0 (pre IV infusion & post IV infusion), month 1-12 visits and month 16 visit | — |
Secondary
| Measure | Time frame |
|---|---|
| Significant differences among interventional group and control group in the following parameter. • The change in uPCR measured on natural log scale from 24-hour urine collection or the intended 24-hour urine collection [At months 9 and 16 (ie, 5 months following the final [12th] monthly dose administration)] Significant differences among interventional group and control group in the following parameter. * The change in 24-hour urine protein excretion [At months 9, 12, and 16] Significant differences among interventional group and control group in the following parameter. •Number of participants in each group achieving greater than or equal to 30% decline from baseline in uPCR [At months 9, 12, and 16] Significant differences among interventional group and control group in the following parameter. •Number of participants in each group with clinical remission, defined as reduction in 24-hour urine protein excretion to < 300 mg/day for at least 3 consecutive months [ During 12 months] Significant differences among interventional group and control group in the following parameter. The change from baseline eGFR [At months 12 and 16] | — |
Countries
Aland Islands
Contacts
Public ContactDr. C.A. Herath
Consultant Nephrologist
Outcome results
None listed