Safety and Efficacy Study of VIS649 for IgA Nephropathy

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Multiple Dose Study to Evaluate the Efficacy and Safety of VIS649 in Participants With Immunoglobulin A (IgA) Nephropathy

The purpose of this study is to evaluate the efficacy and safety of VIS649 in participants with immunoglobulin A (IgA) Nephropathy (IgAN)

Study Overview

• Status: Completed
• Conditions: Immunoglobulin A Nephropathy; Glomerular Disease; IgAN
• Intervention / Treatment: Drug: Dose-Placebo; Drug: Low Dose-VIS649; Drug: Medium Dose-VIS649; Drug: High Dose-VIS649

Detailed Description

This is a Phase 2, double-blind, randomized, placebo-controlled study in patients aged 18 years and above with biopsy confirmed diagnosis of IgAN. The study is designed to test the safety and effectiveness of multiple doses of VIS649. The main objectives are to evaluate the safety and tolerability of VIS649 and to evaluate the dose response of different doses of VIS649 by measuring proteinuria.

The study is comprised of three main periods, Screening, Treatment (12 months) and Follow-Up (4 months). Approximately 144 patients will be enrolled. The findings from this study will form the basis for subsequent clinical development of VIS649.

VIS649 is a humanized immunoglobulin G (IgG2) monoclonal antibody that binds to and blocks the biological actions of the cytokine A PRoliferation Inducing Ligand (APRIL), a key factor in the production of aberrantly glycosylated IgA1 (a-g- IgA1), which is critical to the pathogenesis of IgAN.

• Study Type: Interventional
• Enrollment (Actual): 155
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • New Lambton Heights, New South Wales, Australia, 2305
      • Visterra Investigational Site
    • Saint Leonards, New South Wales, Australia, 2065
      • Visterra Investigational Site
  • Queensland
    • Nambour, Queensland, Australia, 4560
      • Visterra Investigational Site
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Visterra Investigational Site
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Visterra Investigational Site
  • Ontario
    • Brampton, Ontario, Canada, L6R 3J7
      • Visterra Investigational Site
  • Quebec
    • Montréal, Quebec, Canada, H4A 3J1
      • Visterra Investigational Site
• Hong Kong
  • Hong Kong, Hong Kong
    • Visterra Investigational Site
  • Kowloon, Hong Kong, 999077
    • Visterra Investigational Site
  • Tsuen Wan, Hong Kong
    • Visterra Investigational Site
  • HK
    • Hong Kong, HK, Hong Kong
      • Visterra Investigational Site
• India
  • CH
    • Chandigarh, CH, India, 160012
      • Visterra Investigational Site
  • DL
    • New Delhi, DL, India, 110060
      • Visterra Investigational Site
  • KA
    • Bangalore, KA, India, 560054
      • Visterra Investigational Site
    • Bengaluru, KA, India, 560034
      • Visterra Investigational Site
    • Manipala, KA, India, 576104
      • Visterra Investigational Site
  • KL
    • Kozhikode, KL, India, 673008
      • Visterra Investigational Site
    • Thiruvananthapuram, KL, India, 695011
      • Visterra Investigational Site
  • TG
    • Hyderabad, TG, India, 500012
      • Visterra Investigational Site
    • Hyderabad, TG, India, 500082
      • Visterra Investigational Site
  • TN
    • Vellore, TN, India, 632004
      • Visterra Investigational Site
  • UP
    • Raebareli, UP, India, 226014
      • Visterra Investigational Site
• Japan
  • Ashikaga-Shi, Japan, 326-0843
    • Visterra Investigational Site
  • Bunkyō-Ku, Japan, 113-8431
    • Visterra Investigational Site
  • Kashihara-shi, Japan, 634-8522
    • Visterra Investigational Site
  • Minato-Ku, Japan, 470-1192
    • Visterra Investigational Site
  • Nerima Ku, Japan, 177-8521
    • Visterra Investigational Site
  • Niigata Shi, Japan, 951-8520
    • Visterra Investigational Site
  • Shinjuku-Ku, Japan, 162-8666
    • Visterra Investigational Site
  • Tsukuba Shi, Japan, 305-876
    • Visterra Investigational Site
  • Urayasu-Shi, Japan, 279-0021
    • Visterra Investigational Site
  • Aichi
    • Toyoake-shi, Aichi, Japan, 470-1192
      • Visterra Investigational Site
  • Tochigi
    • Ashikaga, Tochigi, Japan, 326-0843
      • Visterra Investigational Site
• Korea, Republic of
  • Anyang, Korea, Republic of, 431-070
    • Visterra Investigational Site
  • Dongdaemun-gu, Korea, Republic of, 130-872
    • Visterra Investigational Site
  • Gangdong, Korea, Republic of, 5355
    • Visterra Investigational Site
  • Hwaseong-si, Korea, Republic of, 18450
    • Visterra Investigational Site
  • Seongnam-si, Korea, Republic of, 13620
    • Visterra Investigational Site
  • Seoul, Korea, Republic of, 05030
    • Visterra Investigational Site
  • Seoul, Korea, Republic of, 3080
    • Visterra Investigational Site
  • Seoul, Korea, Republic of, 3722
    • Visterra Investigational Site
  • Gyeonggi-do
    • Anyang, Gyeonggi-do, Korea, Republic of, 14068
      • Visterra Investigational Site
• Malaysia
  • Klang, Malaysia, 41200
    • Visterra Investigational Site
  • Kuala Lumpur, Malaysia, 56000
    • Visterra Investigational Site
  • Kuala Lumpur, Malaysia, 59100
    • Visterra Investigational Site
  • Kuantan, Malaysia, 25100
    • Visterra Investigational Site
  • Seremban, Malaysia, 70300
    • Visterra Investigational Site
• Philippines
  • Diliman, Philippines, 1101
    • Visterra Investigational Site
  • Quezon City, Philippines, 1102
    • Visterra Investigational Site
• Singapore
  • Singapore, Singapore, 169608
    • Visterra Investigational Site
  • Singapore, Singapore, 308433
    • Visterra Investigational Site
• Spain
  • Barcelona, Spain, 8025
    • Visterra Investigational Site
  • Madrid, Spain, 28034
    • Visterra Investigational Site
  • Sevilla, Spain, 41013
    • Visterra Investigational Site
  • Valencia, Spain, 46017
    • Visterra Investigational Site
  • B
    • L'Hospitalet De Llobregat, B, Spain, 8907
      • Visterra Investigational Site
  • CB
    • Santander, CB, Spain, 39010
      • Visterra Investigational Site
  • CO
    • Córdoba, CO, Spain, 14004
      • Visterra Investigational Site
  • SE
    • Sevilla, SE, Spain, 41009
      • Visterra Investigational Site
• Sri Lanka
  • Colombo, Sri Lanka, 800
    • Visterra Investigational Site
  • Kandy, Sri Lanka, 20000
    • Visterra Investigational Site
  • Nugegoda, Sri Lanka
    • Visterra Investigational Site
• Taiwan
  • Kaohsiung, Taiwan, 82445
    • Visterra Investigational Site
  • Kaohsiung, Taiwan, 83301
    • Visterra Investigational Site
  • Keelung, Taiwan, 20104
    • Visterra Investigational Site
  • New Taipei City, Taiwan, 23142
    • Visterra Investigational Site
  • New Taipei City, Taiwan, 23561
    • Visterra Investigational Site
  • Xitun, Taiwan, 40705
    • Visterra Investigational Site
• Thailand
  • Bangkok, Thailand, 10310
    • Visterra Investigational Site
  • Chiang Mai, Thailand, 50200
    • Visterra Investigational Site
  • Ratchathewi, Thailand, 10400
    • Visterra Investigational Site
• United Kingdom
  • Bradford, United Kingdom, BD5 0NA
    • Visterra Investigational Site
  • London, United Kingdom, E11BB
    • Visterra Investigational Site
  • London, United Kingdom, SE5 9RS
    • Visterra Investigational Site
  • London, United Kingdom, W12 0HS
    • Visterra Investigational Site
  • Salford, United Kingdom, M6 8HD
    • Visterra Investigational Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Visterra Investigational Site
  • California
    • Los Angeles, California, United States, 90027-5969
      • Visterra Investigational Site
    • Oxnard, California, United States, 93036
      • Visterra Investigational Site
    • Palo Alto, California, United States, 94305
      • Visterra Investigational Site
    • Stanford, California, United States, 94305-2200
      • Visterra Investigational Site
  • Colorado
    • Denver, Colorado, United States, 80230
      • Visterra Investigational Site
  • Georgia
    • Lawrenceville, Georgia, United States, 30046
      • Visterra Investigational Site
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Visterra Investigational Site
    • New Orleans, Louisiana, United States, 70121-2429
      • Visterra Investigational Site
  • Maryland
    • Baltimore, Maryland, United States, 21201-1544
      • Visterra Investigational Site
  • Mississippi
    • Tupelo, Mississippi, United States, 38801
      • Visterra Investigational Site
  • New York
    • New York, New York, United States, 10016
      • Visterra Investigational Site
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Visterra Investigational Site
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Visterra Investigational Site
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18017
      • Visterra Investigational Site
  • Texas
    • Houston, Texas, United States, 77030-4202
      • Visterra Investigational Site
    • Houston, Texas, United States, 77054-2854
      • Visterra Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 ≥ 18 years of age at the time of signing the informed consent.
2. Participant must have 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. Participants must have screening uPCR ≥ 0.75 g/g measured from a 24-hour urine or 24-hour urine protein ≥ 1.0 g/d, as measured from 24-hour urine collection. 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. Participants must have eGFR ≥ 45 mL/min/1.73 m².
6. Participant's serum Ig values must meet specified criteria
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 and is willing to give voluntary written informed consent

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.
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 as defined in the protocol.
5. Participant has nephrotic syndrome.
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 within 16 weeks of initial screening.
10. Participant has received treatment with a systemic immunosuppressive agents within 16 weeks of initial screening.
11. Participant has any chronic infectious disease.
12. Participant has acute infectious disease at the time of screening.
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)
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.
21. Participant has known cirrhosis or liver dysfunction, defined as presence of coagulopathy, platelet count < 100,000/μL or alanine aminotransferase > 3× 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 of the participant, in the opinion of the Investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo (0.9% NaCl) will be administered IV	Drug: Dose-Placebo; Unit Dose Strength - 0.9%.
Experimental: Low Dose - VIS649; Low dose of VIS649 administered IV	Drug: Low Dose-VIS649; Dose Level = Low
Experimental: Medium Dose - VIS649; Medium dose of VIS649 administered IV	Drug: Medium Dose-VIS649; Dose Level = Medium
Experimental: High Dose - VIS649; High dose of VIS649 administered IV	Drug: High Dose-VIS649; Dose Level = High

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Assessment	Incidence of adverse events graded by severity	12 months
Efficacy Objective--effect on Proteinuria of repeated doses of VIS649 added to SOC (ACEI/ARB therapy) vs. SOC	Change from baseline in uPCR (Urine protein/creatinine ratio) measured on natural log scale from 24-hour urine collection.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of repeated doses of VIS649 added to SOC (ACEI/ARB therapy) vs. SOC plus placebo	Change from baseline in uPCR (Urine protein/creatinine ratio)	9 months
Efficacy of repeated doses of VIS649 added to SOC (ACEI/ARB therapy) vs. SOC plus placebo	Change from baseline in uPCR (Urine protein/creatinine ratio)	16 months
Efficacy of repeated doses of VIS649 added to SOC (ACEI/ARB therapy) vs. SOC on protein excretion	Change from baseline in 24-hour urine protein excretion	9 months
Efficacy of repeated doses of VIS649 added to SOC (ACEI/ARB therapy) vs. SOC on protein excretion	Change from baseline in 24-hour urine protein excretion	12 months
Efficacy of repeated doses of VIS649 added to SOC (ACEI/ARB therapy) vs. SOC on protein excretion	Change from baseline in 24-hour urine protein excretion	16 months
Efficacy of repeated doses of VIS649 added to SOC (ACEI/ARB therapy) vs. SOC in achieving ≥ 30% decline from baseline in uPCR	Number of patients with ≥ 30% decline from baseline in uPCR	9 months
Efficacy of repeated doses of VIS649 added to SOC (ACEI/ARB therapy) vs. SOC in achieving ≥ 30% decline from baseline in uPCR	Number of patients with ≥ 30% decline from baseline in uPCR	12 months
Efficacy of repeated doses of VIS649 added to SOC (ACEI/ARB therapy) vs. SOC in achieving ≥ 30% decline from baseline in uPCR	Number of patients with ≥ 30% decline from baseline in uPCR	16 months
Efficacy of repeated doses of VIS649 added to SOC (ACEI/ARB therapy) vs. SOC on proteinuria	Number of patients meeting protocol-defined criteria for remission in 24-hour urine protein excretion for protocol-specified period	up to 16 months
Efficacy of repeated doses of VIS649 added to SOC (ACEI/ARB therapy) vs. SOC on kidney function.	Change from baseline in participant's eGFR (Estimated glomerular filtration rate).	12 months
Efficacy of repeated doses of VIS649 added to SOC (ACEI/ARB therapy) vs. SOC on kidney function.	Change from baseline in participant's eGFR (Estimated glomerular filtration rate).	16 months
Pharmacodynamics of repeated doses of VIS649 added to SOC (ACEI/ARB therapy) vs. SOC in total serum IgA, IgG and IgM concentrations	Change from baseline in participant's serum Ig concentrations	9 months
Pharmacodynamics of repeated doses of VIS649 added to SOC (ACEI/ARB therapy) vs. SOC in total serum IgA, IgG and IgM concentrations	Change from baseline in participant's serum Ig concentrations	12 months
Pharmacodynamics of repeated doses of VIS649 added to SOC (ACEI/ARB therapy) vs. SOC in total serum IgA, IgG and IgM concentrations	Change from baseline in participant's serum Ig concentrations	16 months
Serum PK parameters	Measurement of circulating VIS649 concentrations	up to month 16
Serum anti-drug-antibody (ADA)	Measurement of circulating antibodies to VIS649	up to 16 months

Collaborators and Investigators

• Sponsor: Visterra, Inc.
• Investigators: Study Director: David Oldach, M.D., FIDSA, Visterra, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2020
• Primary Completion (Actual): May 19, 2023
• Study Completion (Actual): June 18, 2023

Study Registration Dates

• First Submitted: February 10, 2020
• First Submitted That Met QC Criteria: February 25, 2020
• First Posted (Actual): February 27, 2020

Study Record Updates

• Last Update Posted (Actual): October 27, 2023
• Last Update Submitted That Met QC Criteria: October 26, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Immune System Diseases; Autoimmune Diseases; Kidney Diseases; Proteinuria; Immunoglobulins; Nephritis; Physiological Effects of Drugs; Antibodies; Glomerulonephritis; Immunologic Factors; Immunoglobulin A; Glomerulonephritis, IGA; VIS649
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Urologic Diseases; Nephritis; Glomerulonephritis; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Glomerulonephritis, IGA
• Other Study ID Numbers: VIS649-201; 2019-002531-29 (EudraCT Number); U1111-1263-1268 (Other Identifier: Universal Trial Number (UTN))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No