Clinical trial NCT04287985: Safety and Efficacy Study of VIS649 for IgA Nephropathy
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Immunoglobulin A Nephropathy
Glomerular Disease
IgAN
Keywords: VIS649
Kidney Diseases
Glomerulonephritis, IGA
Glomerulonephritis
Nephritis
Autoimmune Diseases
Immune System Diseases
Immunoglobulins
Antibodies
Immunoglobulin A
Immunologic Factors
Physiological Effects of Drugs
Proteinuria
Lead sponsor: Visterra, Inc.
Sponsor class: INDUSTRY
First posted: 2020-02-27
Enrollment: 155
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility 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 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 using the CKD-EPI formula.
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.

Primary outcomes:
measure: Number of Participants With Adverse Events Graded by Severity
timeFrame: Baseline to End of Study (16 months)
measure: Changes From Baseline in Clinical Laboratory Tests
timeFrame: Baseline to End of Study (16 months)
measure: Clinically Meaningful Changes From Baseline in Vital Signs
timeFrame: Baseline to End of Study (16 months)
measure: Clinically Significant Physical Examinations
timeFrame: Baseline to End of Study (16 months)
measure: Change From Baseline in uPCR: Month 12
timeFrame: 12 months
Secondary outcomes:
measure: Change From Baseline in uPCR: Months 9 and 16
timeFrame: Baseline to 9 months and 16 months (16 months total)
measure: Change in 24-hour Urine Protein Excretion: Months 12 and 16
timeFrame: 16 months
measure: Participants Achieving a Greater Than or Equal to 30% Decline From Baseline in uPCR at Months 9, 12, and 16
timeFrame: Baseline to 9,12, and 16 months (16 months total)
measure: Participants in Each Group Achieving Clinical Remission
timeFrame: Baseline to End of Study (16 months)
measure: Change From Baseline in eGFR at Months 9, 12, and 16
timeFrame: Baseline to 12 and 16 months
measure: Percent Change From Baseline in Total Serum IgA, IgG, and IgM Concentrations at Months 12 and 16
timeFrame: Baseline to 12 and 16 months
measure: Mean Serum PK Parameters at Month 0 and Month 11: Cmax
timeFrame: Months 0 and 11
measure: Median Serum PK Parameters at Month 0 and Month 11: Tmax
timeFrame: Month 0 and Month 11
measure: Mean Serum PK Parameters at Month 0: AUC0-inf and AUC0-30
timeFrame: Month 0
measure: Mean Serum PK Parameters at Month 0 and Month 11: t1/2z
timeFrame: Month 0 and Month 11
measure: Median Serum PK Parameters at Month 0: CL
timeFrame: Month 0
measure: Mean Serum PK Parameters at Month 0: Vz
timeFrame: Month 0
measure: Mean Serum PK Parameters at Month 11: AUCτ
timeFrame: Month 11
measure: Mean Serum PK Parameters at Month 11: Vss
timeFrame: Month 11
measure: Mean Serum PK Parameters at Month 11: CLss
timeFrame: Month 11
measure: Mean Serum PK Parameters at Month 11: Rac[AUC0-30]
timeFrame: Month 11
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Visterra Investigational Site
state: Alabama
city: Los Angeles
country: United States
facility: Visterra Investigational Site
state: California
city: Oxnard
country: United States
facility: Visterra Investigational Site
state: California
city: Palo Alto
country: United States
facility: Visterra Investigational Site
state: California
city: Stanford
country: United States
facility: Visterra Investigational Site
state: California
city: Denver
country: United States
facility: Visterra Investigational Site
state: Colorado
city: Lawrenceville
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facility: Visterra Investigational Site
state: Georgia
city: Baton Rouge
country: United States
facility: Visterra Investigational Site
state: Louisiana
city: New Orleans
country: United States
facility: Visterra Investigational Site
state: Louisiana
city: Baltimore
country: United States
facility: Visterra Investigational Site
state: Maryland
city: Tupelo
country: United States
facility: Visterra Investigational Site
state: Mississippi
city: New York
country: United States
facility: Visterra Investigational Site
state: New York
city: Chapel Hill
country: United States
facility: Visterra Investigational Site
state: North Carolina
city: Columbus
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facility: Visterra Investigational Site
state: Ohio
city: Bethlehem
country: United States
facility: Visterra Investigational Site
state: Pennsylvania
city: Houston
country: United States
facility: Visterra Investigational Site
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city: Houston
country: United States
facility: Visterra Investigational Site
state: Texas
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facility: Visterra Investigational Site
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city: Saint Leonards
country: Australia
facility: Visterra Investigational Site
state: New South Wales
city: Nambour
country: Australia
facility: Visterra Investigational Site
state: Queensland
city: Nedlands
country: Australia
facility: Visterra Investigational Site
state: Western Australia
city: Calgary
country: Canada
facility: Visterra Investigational Site
state: Alberta
city: Brampton
country: Canada
facility: Visterra Investigational Site
state: Ontario
city: Montréal
country: Canada
facility: Visterra Investigational Site
state: Quebec
city: Hong Kong
country: Hong Kong
facility: Visterra Investigational Site
state: HK
city: Hong Kong
country: Hong Kong
facility: Visterra Investigational Site
city: Kowloon
country: Hong Kong
facility: Visterra Investigational Site
city: Tsuen Wan
country: Hong Kong
facility: Visterra Investigational Site
city: Chandigarh
country: India
facility: Visterra Investigational Site
state: CH
city: New Delhi
country: India
facility: Visterra Investigational Site
state: DL
city: Bangalore
country: India
facility: Visterra Investigational Site
state: KA
city: Bengaluru
country: India
facility: Visterra Investigational Site
state: KA
city: Manipala
country: India
facility: Visterra Investigational Site
state: KA
city: Kozhikode
country: India
facility: Visterra Investigational Site
state: KL
city: Thiruvananthapuram
country: India
facility: Visterra Investigational Site
state: KL
city: Hyderabad
country: India
facility: Visterra Investigational Site
state: TG
city: Hyderabad
country: India
facility: Visterra Investigational Site
state: TG
city: Vellore
country: India
facility: Visterra Investigational Site
state: TN
city: Raebareli
country: India
facility: Visterra Investigational Site
state: UP
city: Toyoake-shi
country: Japan
facility: Visterra Investigational Site
state: Aichi
city: Tokyo
country: Japan
facility: Visterra Investigational Site
state: Nerima Ku
city: Ashikaga
country: Japan
facility: Visterra Investigational Site
state: Tochigi
city: Ashikaga-Shi
country: Japan
facility: Visterra Investigational Site
city: Bunkyō-Ku
country: Japan
facility: Visterra Investigational Site
city: Kashihara-shi
country: Japan
facility: Visterra Investigational Site
city: Minato-Ku
country: Japan
facility: Visterra Investigational Site
city: Niigata Shi
country: Japan
facility: Visterra Investigational Site
city: Shinjuku-Ku
country: Japan
facility: Visterra Investigational Site
city: Tsukuba Shi
country: Japan
facility: Visterra Investigational Site
city: Urayasu-Shi
country: Japan
facility: Visterra Investigational Site
city: Seoul
country: Korea, Republic of
facility: Visterra Investigational Site
state: Dongdaemun-gu
city: Anyang
country: Korea, Republic of
facility: Visterra Investigational Site
state: Gyeonggi-do
city: Anyang
country: Korea, Republic of
facility: Visterra Investigational Site
city: Gangdong
country: Korea, Republic of
facility: Visterra Investigational Site
city: Hwaseong-si
country: Korea, Republic of
facility: Visterra Investigational Site
city: Seongnam-si
country: Korea, Republic of
facility: Visterra Investigational Site
city: Seoul
country: Korea, Republic of
facility: Visterra Investigational Site
city: Seoul
country: Korea, Republic of
facility: Visterra Investigational Site
city: Seoul
country: Korea, Republic of
facility: Visterra Investigational Site
city: Klang
country: Malaysia
facility: Visterra Investigational Site
city: Kuala Lumpur
country: Malaysia
facility: Visterra Investigational Site
city: Kuala Lumpur
country: Malaysia
facility: Visterra Investigational Site
city: Kuantan
country: Malaysia
facility: Visterra Investigational Site
city: Seremban
country: Malaysia
facility: Visterra Investigational Site
city: Diliman
country: Philippines
facility: Visterra Investigational Site
city: Quezon City
country: Philippines
facility: Visterra Investigational Site
city: Singapore
country: Singapore
facility: Visterra Investigational Site
city: Singapore
country: Singapore
facility: Visterra Investigational Site
city: L'Hospitalet De Llobregat
country: Spain
facility: Visterra Investigational Site
state: B
city: Santander
country: Spain
facility: Visterra Investigational Site
state: CB
city: Córdoba
country: Spain
facility: Visterra Investigational Site
state: CO
city: Sevilla
country: Spain
facility: Visterra Investigational Site
state: SE
city: Barcelona
country: Spain
facility: Visterra Investigational Site
city: Madrid
country: Spain
facility: Visterra Investigational Site
city: Sevilla
country: Spain
facility: Visterra Investigational Site
city: Valencia
country: Spain
facility: Visterra Investigational Site
city: Colombo
country: Sri Lanka
facility: Visterra Investigational Site
city: Kandy
country: Sri Lanka
facility: Visterra Investigational Site
city: Nugegoda
country: Sri Lanka
facility: Visterra Investigational Site
city: Kaohsiung
country: Taiwan
facility: Visterra Investigational Site
city: Kaohsiung
country: Taiwan
facility: Visterra Investigational Site
city: Keelung
country: Taiwan
facility: Visterra Investigational Site
city: New Taipei City
country: Taiwan
facility: Visterra Investigational Site
city: New Taipei City
country: Taiwan
facility: Visterra Investigational Site
city: Xitun
country: Taiwan
facility: Visterra Investigational Site
city: Bangkok
country: Thailand
facility: Visterra Investigational Site
city: Chiang Mai
country: Thailand
facility: Visterra Investigational Site
city: Ratchathewi
country: Thailand
facility: Visterra Investigational Site
city: Bradford
country: United Kingdom
facility: Visterra Investigational Site
city: London
country: United Kingdom
facility: Visterra Investigational Site
city: London
country: United Kingdom
facility: Visterra Investigational Site
city: London
country: United Kingdom
facility: Visterra Investigational Site
city: Salford
country: United Kingdom
facility: Visterra Investigational Site
Study officials:
affiliation: Visterra, Inc.
name: Asher Schachter, M.D.
role: STUDY_DIRECTOR
References:
citation: Mathur M, Barratt J, Chacko B, Chan TM, Kooienga L, Oh KH, Sahay M, Suzuki Y, Wong MG, Yarbrough J, Xia J, Pereira BJG; ENVISION Trial Investigators Group. A Phase 2 Trial of Sibeprenlimab in Patients with IgA Nephropathy. N Engl J Med. 2024 Jan 4;390(1):20-31. doi: 10.1056/NEJMoa2305635. Epub 2023 Nov 2.