Safety and Efficacy Study of VIS649 for IgA Nephropathy

Immunoglobulin A Nephropathy Clinical Trial

Official title:

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

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
• 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
• 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.

Related Conditions & MeSH terms

• Glomerular Disease
• Glomerulonephritis, IGA
• IgAN
• Immunoglobulin A Nephropathy
• Kidney Diseases

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