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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT04287985
Other study ID # VIS649-201
Secondary ID 2019-002531-29U1
Status Completed
Phase Phase 2
First received
Last updated
Start date July 20, 2020
Est. completion date June 18, 2023

Study information

Verified date October 2023
Source Visterra, Inc.
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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


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.


Recruitment information / eligibility

Status Completed
Enrollment 155
Est. completion date June 18, 2023
Est. primary completion date May 19, 2023
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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 Design


Intervention

Drug:
Dose-Placebo
Unit Dose Strength - 0.9%.
Low Dose-VIS649
Dose Level = Low
Medium Dose-VIS649
Dose Level = Medium
High Dose-VIS649
Dose Level = High

Locations

Country Name City State
Australia Visterra Investigational Site Nambour Queensland
Australia Visterra Investigational Site Nedlands Western Australia
Australia Visterra Investigational Site New Lambton Heights New South Wales
Australia Visterra Investigational Site Saint Leonards New South Wales
Canada Visterra Investigational Site Brampton Ontario
Canada Visterra Investigational Site Calgary Alberta
Canada Visterra Investigational Site Montréal Quebec
Hong Kong Visterra Investigational Site Hong Kong HK
Hong Kong Visterra Investigational Site Hong Kong
Hong Kong Visterra Investigational Site Kowloon
Hong Kong Visterra Investigational Site Tsuen Wan
India Visterra Investigational Site Bangalore KA
India Visterra Investigational Site Bengaluru KA
India Visterra Investigational Site Chandigarh CH
India Visterra Investigational Site Hyderabad TG
India Visterra Investigational Site Hyderabad TG
India Visterra Investigational Site Kozhikode KL
India Visterra Investigational Site Manipala KA
India Visterra Investigational Site New Delhi DL
India Visterra Investigational Site Raebareli UP
India Visterra Investigational Site Thiruvananthapuram KL
India Visterra Investigational Site Vellore TN
Japan Visterra Investigational Site Ashikaga Tochigi
Japan Visterra Investigational Site Ashikaga-Shi
Japan Visterra Investigational Site Bunkyo-Ku
Japan Visterra Investigational Site Kashihara-shi
Japan Visterra Investigational Site Minato-Ku
Japan Visterra Investigational Site Nerima Ku
Japan Visterra Investigational Site Niigata Shi
Japan Visterra Investigational Site Shinjuku-Ku
Japan Visterra Investigational Site Toyoake-shi Aichi
Japan Visterra Investigational Site Tsukuba Shi
Japan Visterra Investigational Site Urayasu-Shi
Korea, Republic of Visterra Investigational Site Anyang Gyeonggi-do
Korea, Republic of Visterra Investigational Site Anyang
Korea, Republic of Visterra Investigational Site Dongdaemun-gu
Korea, Republic of Visterra Investigational Site Gangdong
Korea, Republic of Visterra Investigational Site Hwaseong-si
Korea, Republic of Visterra Investigational Site Seongnam-si
Korea, Republic of Visterra Investigational Site Seoul
Korea, Republic of Visterra Investigational Site Seoul
Korea, Republic of Visterra Investigational Site Seoul
Malaysia Visterra Investigational Site Klang
Malaysia Visterra Investigational Site Kuala Lumpur
Malaysia Visterra Investigational Site Kuala Lumpur
Malaysia Visterra Investigational Site Kuantan
Malaysia Visterra Investigational Site Seremban
Philippines Visterra Investigational Site Diliman
Philippines Visterra Investigational Site Quezon City
Singapore Visterra Investigational Site Singapore
Singapore Visterra Investigational Site Singapore
Spain Visterra Investigational Site Barcelona
Spain Visterra Investigational Site Córdoba CO
Spain Visterra Investigational Site L'Hospitalet De Llobregat B
Spain Visterra Investigational Site Madrid
Spain Visterra Investigational Site Santander CB
Spain Visterra Investigational Site Sevilla
Spain Visterra Investigational Site Sevilla SE
Spain Visterra Investigational Site Valencia
Sri Lanka Visterra Investigational Site Colombo
Sri Lanka Visterra Investigational Site Kandy
Sri Lanka Visterra Investigational Site Nugegoda
Taiwan Visterra Investigational Site Kaohsiung
Taiwan Visterra Investigational Site Kaohsiung
Taiwan Visterra Investigational Site Keelung
Taiwan Visterra Investigational Site New Taipei City
Taiwan Visterra Investigational Site New Taipei City
Taiwan Visterra Investigational Site Xitun
Thailand Visterra Investigational Site Bangkok
Thailand Visterra Investigational Site Chiang Mai
Thailand Visterra Investigational Site Ratchathewi
United Kingdom Visterra Investigational Site Bradford
United Kingdom Visterra Investigational Site London
United Kingdom Visterra Investigational Site London
United Kingdom Visterra Investigational Site London
United Kingdom Visterra Investigational Site Salford
United States Visterra Investigational Site Baltimore Maryland
United States Visterra Investigational Site Baton Rouge Louisiana
United States Visterra Investigational Site Bethlehem Pennsylvania
United States Visterra Investigational Site Birmingham Alabama
United States Visterra Investigational Site Chapel Hill North Carolina
United States Visterra Investigational Site Columbus Ohio
United States Visterra Investigational Site Denver Colorado
United States Visterra Investigational Site Houston Texas
United States Visterra Investigational Site Houston Texas
United States Visterra Investigational Site Lawrenceville Georgia
United States Visterra Investigational Site Los Angeles California
United States Visterra Investigational Site New Orleans Louisiana
United States Visterra Investigational Site New York New York
United States Visterra Investigational Site Oxnard California
United States Visterra Investigational Site Palo Alto California
United States Visterra Investigational Site Stanford California
United States Visterra Investigational Site Tupelo Mississippi

Sponsors (1)

Lead Sponsor Collaborator
Visterra, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Hong Kong,  India,  Japan,  Korea, Republic of,  Malaysia,  Philippines,  Singapore,  Spain,  Sri Lanka,  Taiwan,  Thailand,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Safety Assessment Incidence of adverse events graded by severity 12 months
Primary 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 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
Secondary 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
Secondary 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
Secondary 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
Secondary 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
Secondary 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
Secondary 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
Secondary 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
Secondary 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
Secondary 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
Secondary 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
Secondary 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
Secondary 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
Secondary 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
Secondary Serum PK parameters Measurement of circulating VIS649 concentrations up to month 16
Secondary Serum anti-drug-antibody (ADA) Measurement of circulating antibodies to VIS649 up to 16 months
See also
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