Phase 2 Study of VIS649 for IgA Nephropathy

JRCT ID: jRCT2041210130

Registered date:19/01/2022

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Immunoglobulin A(IgA) Nephropathy
• Date of first enrollment: 30/11/2020
• Target sample size: 19
• Countries of recruitment: The United States,Japan,Singapore,Japan,United Kingdom,Japan,Canada,Japan,India,Japan,Malaysia,Japan,Hong Kong,Japan,Australia,Japan,Philippines,Japan,Spain,Japan,South Korea,Japan,Thailand,Japan,Taiwan,Japan,Sri Lanka,Japan
• Study type: Interventional
• Intervention(s): VIS649 or placebo will be administered as a single, monthly IV infusion for 12 monthly doses.

Outcome(s)

Primary Outcome

Safety:
- AEs graded by severity, clinical laboratory tests, vital sign measurements, and physical examinations
Efficacy:
- Change from baseline in uPCR (measured on natural log scale from 24-hour urine collection or the intended 24-hour urine collection) at Month 12 (ie, approximately 30 days after the 12th dose is administered)

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. Participant is a male or female >= 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 local SOC and applicable guidelines, for at least 3 months preceding screening. Participants should optimally be on at least 50% of the maximum recommended dose of these agents; however, if a participant is on their maximally tolerated dose (and this is < 50% of the maximum recommended dose) and has been on this dose for at least 3 months, they may be enrolled. 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 local SOC and applicable guidelines.
4. Participant has screening uPCR >= 0.75 g/g measured from a 24-hour urine (or an intended 24 hour urine sample) or 24-hour urine protein >= 1.0 g/d, as measured from 24 hour urine collection (or an intended 24 hour urine sample).
- 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. Re-testing may be allowed if it is determined that the participant was not in steady state after consultation with the medical monitor.
5. Participant has eGFR >= 45 mL/min/1.73 m2, calculated using the CKD-EPI formula.
- Retesting may be allowed if it is determined that the participant was not in steady state after consultation with the medical monitor.
- Participants with eGFR >= 30 mL/min/1.73 m2 and < 45 mL/min/1.73 m2 may also undergo screening, if they have undergone a kidney biopsy within 12 months of the date of initial screening and do not have >= 50% tubulo-interstitial fibrosis (T2 if using MEST-C score) or crescents in > 25% of glomeruli (C2 if using MEST-C score).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. Participants serum Ig values must meet the following criteria:
- IgG: >= 700 mg/dL
- IgM: >= 37 mg/dL
- IgA: >= 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.
9. Participant or a legally authorized representative is able to understand the purpose and risks of the study and is willing to give voluntary written informed consent as described.

Exclude criteria

1. Participant has secondary forms of IgAN as defined by the treating physician (eg, Henoch Schonlein purpura (IgA vasculitis), 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 Oxford IgAN 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 < 2.5 g/dL), hyperlipidemia (total cholesterol > 350 mg/dL), and edema. Participants with isolated nephrotic range proteinuria (>3.5 g/d) will be eligible.
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 treatment with systemic corticosteroid therapy (excluding topical, ophthalmic, per rectum, or inhaled corticosteroids) within 16 weeks of initial screening.
10. Participant has received treatment with a systemic immunosuppressive agent (e.g., mycophenolate mofetil, azathioprine, calcineurin inhibitors, cyclophosphamide/cytotoxic agents) within 16 weeks of initial screening.
11. Participant has any chronic infectious disease (eg, chronic urinary tract infection; chronic sinusitis; bronchiectasis; active pulmonary or systemic tuberculosis; chronic viral hepatitis, such as hepatitis C or hepatitis B; or human immunodeficiency virus infection). See Section 4.1 Study Design for further details.
12. Participant has acute infectious disease at the time of screening. Participants may be rescreened 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 < 100,000/uL or alanine aminotransferase > 3x upper limit of normal.
22. Participant has active malignancy or is receiving chemotherapy for malignancy, except for nonmelanoma skin cancers and cervical carcinoma in situ. Participants with prior malignancy who have been documented to be cancer-free for >= 5 years may be enrolled.
23. Participant is planning or scheduled to undergo a tonsillectomy. Prior tonsillectomy is acceptable (if greater than 6 months prior to screening).
24. Participant enrolled in another investigational drug or device study within 3 months prior to initial screening.
25. Participant with a pre-existing illness other than those listed above that, in the opinion of the Investigator, would place the participant at increased risk through participation in this study.
26. Participant is unable to comply with study protocol procedures and/or study visit schedules.
27. Participant with known or suspected alcohol or drug abuse that would compromise their safety or study participation, in the opinion of the Investigator.

Related Information

• Primary Sponsor: Nishioka Tsuyoshi
• Secondary ID(s): NCT04287985