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Safety and Efficacy Study of VIS649 for IgA Nephropathy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04287985
Recruitment Status : Recruiting
First Posted : February 27, 2020
Last Update Posted : January 6, 2021
Sponsor:
Information provided by (Responsible Party):
Visterra, Inc.

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

Condition or disease Intervention/treatment Phase
Immunoglobulin A Nephropathy Glomerular Disease IgAN Drug: Dose-Placebo Drug: Low Dose-VIS649 Drug: Medium Dose-VIS649 Drug: High Dose-VIS649 Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 144 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Patient, Investigator, Care Provider, Outcomes Assessor
Primary Purpose: Treatment
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
Actual Study Start Date : July 20, 2020
Estimated Primary Completion Date : November 15, 2022
Estimated Study Completion Date : December 1, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Diseases

Arms and Interventions
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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


Outcome Measures
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Primary Outcome Measures :
  1. Safety Assessment [ Time Frame: 12 months ]
    Incidence of adverse events graded by severity

  2. Efficacy Objective--effect on Proteinuria of repeated doses of VIS649 added to SOC (ACEI/ARB therapy) vs. SOC [ Time Frame: 12 months ]
    Change from baseline in uPCR (Urine protein/creatinine ratio) measured on natural log scale from 24-hour urine collection.


Secondary Outcome Measures :
  1. Efficacy of repeated doses of VIS649 added to SOC (ACEI/ARB therapy) vs. SOC plus placebo [ Time Frame: 9 months ]
    Change from baseline in uPCR (Urine protein/creatinine ratio)

  2. Efficacy of repeated doses of VIS649 added to SOC (ACEI/ARB therapy) vs. SOC plus placebo [ Time Frame: 16 months ]
    Change from baseline in uPCR (Urine protein/creatinine ratio)

  3. Efficacy of repeated doses of VIS649 added to SOC (ACEI/ARB therapy) vs. SOC on protein excretion [ Time Frame: 9 months ]
    Change from baseline in 24-hour urine protein excretion

  4. Efficacy of repeated doses of VIS649 added to SOC (ACEI/ARB therapy) vs. SOC on protein excretion [ Time Frame: 12 months ]
    Change from baseline in 24-hour urine protein excretion

  5. Efficacy of repeated doses of VIS649 added to SOC (ACEI/ARB therapy) vs. SOC on protein excretion [ Time Frame: 16 months ]
    Change from baseline in 24-hour urine protein excretion

  6. Efficacy of repeated doses of VIS649 added to SOC (ACEI/ARB therapy) vs. SOC in achieving ≥ 30% decline from baseline in uPCR [ Time Frame: 9 months ]
    Number of patients with ≥ 30% decline from baseline in uPCR

  7. Efficacy of repeated doses of VIS649 added to SOC (ACEI/ARB therapy) vs. SOC in achieving ≥ 30% decline from baseline in uPCR [ Time Frame: 12 months ]
    Number of patients with ≥ 30% decline from baseline in uPCR

  8. Efficacy of repeated doses of VIS649 added to SOC (ACEI/ARB therapy) vs. SOC in achieving ≥ 30% decline from baseline in uPCR [ Time Frame: 16 months ]
    Number of patients with ≥ 30% decline from baseline in uPCR

  9. Efficacy of repeated doses of VIS649 added to SOC (ACEI/ARB therapy) vs. SOC on proteinuria [ Time Frame: up to 16 months ]
    Number of patients meeting protocol-defined criteria for remission in 24-hour urine protein excretion for protocol-specified period

  10. Efficacy of repeated doses of VIS649 added to SOC (ACEI/ARB therapy) vs. SOC on kidney function. [ Time Frame: 12 months ]
    Change from baseline in participant's eGFR (Estimated glomerular filtration rate).

  11. Efficacy of repeated doses of VIS649 added to SOC (ACEI/ARB therapy) vs. SOC on kidney function. [ Time Frame: 16 months ]
    Change from baseline in participant's eGFR (Estimated glomerular filtration rate).

  12. Pharmacodynamics of repeated doses of VIS649 added to SOC (ACEI/ARB therapy) vs. SOC in total serum IgA, IgG and IgM concentrations [ Time Frame: 9 months ]
    Change from baseline in participant's serum Ig concentrations

  13. Pharmacodynamics of repeated doses of VIS649 added to SOC (ACEI/ARB therapy) vs. SOC in total serum IgA, IgG and IgM concentrations [ Time Frame: 12 months ]
    Change from baseline in participant's serum Ig concentrations

  14. Pharmacodynamics of repeated doses of VIS649 added to SOC (ACEI/ARB therapy) vs. SOC in total serum IgA, IgG and IgM concentrations [ Time Frame: 16 months ]
    Change from baseline in participant's serum Ig concentrations

  15. Serum PK parameters [ Time Frame: up to month 16 ]
    Measurement of circulating VIS649 concentrations

  16. Serum anti-drug-antibody (ADA) [ Time Frame: up to 16 months ]
    Measurement of circulating antibodies to VIS649


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 ≥ 18 years of age at the time of signing the informed consent.
  2. Participant must have biopsy-confirmed IgAN.
  3. Participant 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 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. 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 stable.
  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 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.
  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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04287985


Contacts
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Contact: Visterra Clinical Trial Information Line 617-498-1070 clinicaltrials@visterrainc.com

Locations
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United States, California
Visterra Investigational Site Recruiting
Palo Alto, California, United States, 94305
Contact: Study Coordinator    617-498-1070    clinicaltrials@visterrainc.com   
United States, Colorado
Visterra Investigational Site Recruiting
Denver, Colorado, United States, 80230
Contact: Study Coordinator    617-498-1070    clinicaltrials@visterrainc.com   
United States, Louisiana
Visterra Investigational Site Recruiting
Baton Rouge, Louisiana, United States, 70808
Contact: Study Coordinator    617-498-1070    clinicaltrials@visterrainc.com   
United States, Mississippi
Visterra Investigational Site Recruiting
Tupelo, Mississippi, United States, 38801
Contact: Study Coordinator    617-498-1070    clinicaltrials@visterrainc.com   
United States, North Carolina
Visterra Investigational Site Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Study Coordinator    617-498-1070    clinicaltrials@visterrainc.com   
United States, Ohio
Visterra Clinical Stie Recruiting
Columbus, Ohio, United States, 43210
Contact: Study Coordinator    617-498-1070    clinicaltrials@visterrainc.com   
United States, Pennsylvania
Visterra Investigational Site Recruiting
Bethlehem, Pennsylvania, United States, 18017
Contact: Study Coordinator    617-498-1070    clinicaltrials@visterrainc.com   
Japan
Visterra Investigational Site Recruiting
Toyoake-shi, Aichi, Japan, 470-1192
Contact: Study Coordinator    +1.617.498.1070    clinicaltrials@visterrainc.com   
Visterra Investigational Site Recruiting
Ashikaga, Tochigi, Japan, 326-0843
Contact: Study Coordinator    +1.617.498.1070    clinicaltrials@visterrainc.com   
Korea, Republic of
Visterra Investigational Site Recruiting
Anyang, Gyeonggi-do, Korea, Republic of, 14068
Contact: Study Coordinator    +1.617.498.1070    clinicaltrials@visterrainc.com   
Visterra Investigational Site Recruiting
Seoul, Korea, Republic of, 05030
Contact: Study Coordinator    +1.617.498-1070    clinicaltrials@visterrainc.com   
Spain
Visterra Investigational Site Recruiting
Sevilla, Spain, 41013
Contact: Study Coordinator    +1.617.498.1070    clinicaltrials@visterrainc.com   
Visterra Investigational Site Recruiting
Valencia, Spain, 46017
Contact: Study Coordinator    +1.617.498.1070    clinicaltrials@visterrainc.com   
Sponsors and Collaborators
Visterra, Inc.
Investigators
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Study Director: David Oldach, M.D., FIDSA Visterra, Inc.
More Information
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Responsible Party: Visterra, Inc.
ClinicalTrials.gov Identifier: NCT04287985    
Other Study ID Numbers: VIS649-201
2019-002531-29 ( EudraCT Number )
U1111-1263-1268 ( Other Identifier: Universal Trial Number (UTN) )
First Posted: February 27, 2020    Key Record Dates
Last Update Posted: January 6, 2021
Last Verified: January 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Visterra, Inc.:
VIS649
Kidney Diseases
Glomerulonephritis, IGA
Glomerulonephritis
Nephritis
Autoimmune Diseases
Immune System Diseases
 Immunoglobulins
Antibodies
Immunoglobulin A
Immunologic Factors
Physiological Effects of Drugs
Proteinuria
Additional relevant MeSH terms:
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Kidney Diseases
Glomerulonephritis, IGA
Urologic Diseases
Glomerulonephritis
 Nephritis
Autoimmune Diseases
Immune System Diseases