ARGX-117 in Deceased Donor Kidney Transplant Recipients at Risk for Delayed Graft Function (VARVARA)

A Phase 2, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Study to Assess the Safety, Efficacy, and Tolerability of ARGX-117 in Improving Allograft Function in Recipients of a Deceased Donor Renal Allograft at Risk for Delayed Graft Function

The main purpose of this study is to evaluate the safety, efficacy and tolerability of ARGX-117 in Deceased Donor Kidney Transplant Recipients at Risk for Delayed Graft Function.

The study consists of 2 parts: part A comprises the main study period, and part B comprises the long-term observational follow-up period. During part A, after the screening period, eligible participants will be randomized to receive either ARGX-117 or placebo, entering the treatment and evaluation period (duration of up to 52 weeks). After the treatment period, participants will enter a follow-up period of up to 12 weeks.

The total study duration varies from approximately 64 weeks up to 5 years post-transplant depending on whether a participant enrols in part B of the study.

Study Overview

• Status: Active, not recruiting
• Conditions: Delayed Graft Function
• Intervention / Treatment: Biological: ARGX-117; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 103
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia, SA 5000
    • Royal Adelaide Hospital
  • Clayton, Australia, 3168
    • Monash Health - Monash Medical Centre
  • Woolloongabba, Australia, QLD 4102
    • Princess Alexandra Hospital
• Austria
  • Innsbruck, Austria, 6020
    • Tirol Kliniken - A.o. Landeskrankenhaus Innsbruck
  • Vienna, Austria, 1090
    • Allgemeines Krankenhaus der Stadt Wien (AKH Wien)
• Belgium
  • Leuven, Belgium, 3000
    • Universitair Ziekenhuis Leuven
• Brazil
  • Coimbra, Brazil, 3004-561
    • Centro Hospitalar e Universitario de Coimbra
  • Fortaleza, Brazil, 60156-290
    • Hospital Geral de Fortaleza
  • Porto Alegre, Brazil, 90020-090
    • Santa Casa de Misericordia de Porto Alegre - Hospital Dom Vicente Scherer
  • São Jose Do Rio Preto, Brazil, 15090-000
    • Hospital de Base
  • São Paulo, Brazil, 05403-000
    • Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP)
• Canada
  • Montreal, Canada, H4A 3J1
    • McGill University Health Centre - Royal Victoria Hospital
  • Montreal, Canada, H1T 2M4
    • Hôpital Maisonneuve-Rosemont - Centre de recherche
  • Vancouver, Canada, V5Z 1M9
    • Vancouver Coastal Health - Vancouver General Hospital Diamond Healthcare Centre
  • Vancouver, Canada, V6Z 1Y6
    • Providence Health Care - St. Pauls Hospital
• France
  • Bordeaux, France, 33076
    • CHU Bordeaux - Groupe Hospitalier Pellegrin
  • Créteil, France, 94000
    • Assistance Publique Hopitaux de Paris (AP-HP) - Hopital Henri Mondor
  • La Tronche, France, 38700
    • CHU Grenoble Alpes - Hopital Michallon
  • Paris, France, 75015
    • Assistance Publique Hopitaux de Paris (AP-HP) - Hopital Necker-Enfants Malades
  • Toulouse, France, 31400
    • CHU de Toulouse - Hopital Rangueil
  • Tours, France, 37000
    • CHRU de Tours - Hôpital Bretonneau
• Italy
  • Bologna, Italy, 40138
    • Azienda Ospedaliero Universitaria di Bologna Policlinico di Sant'Orsola
  • Padua, Italy, 35128
    • Azienda Ospedale Università Padova
  • Torino, Italy, 10126
    • Azienda Ospedaliero Universitaria Citta della Salute e della Scienza di Torino - Presidio Molinette
• Portugal
  • Carnaxide, Portugal, 2790-134
    • Centro Hospitalar de Lisboa Ocidental EPE - Hospital de Santa Cruz
  • Lisbon, Portugal, 1069-099
    • Centro Hospitalar Universitario Lisboa Central EPE - Hospital Curry Cabral
  • Porto, Portugal, 4099-001
    • Centro Hospitalar Universitário de Santo António
• Spain
  • Badalona, Spain, 08916
    • Hospital Universitari Germans Trias i Pujol (HUGTP)
  • Barcelona, Spain, 08003
    • Hospital del Mar
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron
  • Barcelona, Spain, 08025
    • Fundacio Puigvert
  • Granada, Spain, 18014
    • Hospital Universitario Virgen de las Nieves - Hospital General
  • L'Hospitalet de Llobregat, Spain, 08907
    • Hospital Universitari de Bellvitge
  • Valencia, Spain, 46017
    • Hospital Universitari Doctor Peset
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet
• Sweden
  • Gothenburg, Sweden, 41345
    • Sahlgrenska Universitetssjukhuset
  • Uppsala, Sweden, 75185
    • Akademiska Sjukhuset
• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
  • Florida
    • Tampa, Florida, United States, 33606
      • Tampa General Hospital
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois (UI) Health - Outpatient Care Center
  • New Jersey
    • Livingston, New Jersey, United States, 07039
      • Cooperman Barnabas Medical Center
  • New York
    • Buffalo, New York, United States, 14215
      • Erie County Medical Center
    • New York, New York, United States, 10032
      • Columbia University
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University
  • Texas
    • Dallas, Texas, United States, 10267
      • University of Texas Southwestern Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Is at least the local legal age of consent for clinical studies and at least aged 18 years and less than 70 years
• Agree to use contraceptive measures consistent with local regulations
• Are diagnosed with ESRD and have been stable on chronic dialysis for at least 3 months
• Are recipients of de novo or second-time, single kidney transplant from a deceased donor, either DCD (donation after cardiac/circulatory death) or DBD ( (donation after brain death)
• Are ABO compatible with donor allograft, except for type A2 donor to type B recipient kidneys
• Have a negative cross match
• Have received pretransplant vaccinations for: Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae, or are willing to receive the vaccinations approximately 3 to 4 months posttransplant

Exclusion Criteria:

• Any history of prothrombotic disorder or history of thrombosis or hypercoagulable state, excluding vascular access clotting
• Any known history of complement deficiency
• Evidence of peritonitis in participants on peritoneal dialysis
• Received any solid organ, bone marrow, or hematopoietic stem cell transplant, with the exception of prior first kidney transplant
• High risk within the study period for recurrence of underlying renal disease in the opinion of the investigator
• Clinically significant comorbidity, recent major surgery (within 3 months of screening), history of any treatment nonadherence, or intention to have surgery during the study other than kidney transplantation; or any other medical condition that, in the investigator's opinion, would confound the results of the study or put the participant at undue risk
• Clinically significant active bacterial, viral, or fungal infection
• History of malignancy unless considered cured by adequate treatment, with no evidence of recurrence for 5 years or more before first study drug administration. Adequately treated participants with the following cancers can be included at any time: Basal cell or squamous cell skin cancer; Carcinoma in situ of the cervix; Carcinoma in situ of the breast; Incidental histological finding of prostate cancer
• History of current alcohol, drug, or medication abuse as assessed by the investigator
• Pregnant or lactating state or intention to become pregnant during the study

The full list of criteria can be found in the protocol.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ARGX-117; Patients receiving ARGX-117 intravenous infusions	Biological: ARGX-117; Intravenous administration of ARGX-117
Placebo Comparator: Placebo; Patients receiving placebo intravenous infusions	Other: Placebo; Intravenous administration of placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
eGFR at 24 weeks posttransplant	Estimated glomerular filtration rate	Up to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with Delayed Graft Function (DGF)		Up to 52 weeks
iBox score at 52 weeks posttransplant		up to 52 weeks
eGFR at 52 weeks posttransplant	Estimated glomerular filtration rate	up to 52 weeks
Duration of dialysis treatment for DGF within the first 30 days posttransplant		up to 30 days
Proportion of participants who have ongoing dialysis requirement at study day 31		Up to 31 days
CRR at 72 hours posttransplant and on study day 8	Creatinine reduction ratio	up to 8 days
Dialysis-free participant survival through 52 weeks posttransplant		up to 52 weeks
(Death-censored) allograft survival through 52 weeks posttransplant		Up to 52 weeks
Serum concentrations for ARGX 117		up to 64 weeks
Incidence of anti-drug antibodies (ADA) against ARGX-117		up to 64 weeks
Proportion of participants with fDGF	Functional Delayed Graft Function	Up to 52 weeks
Incidence of PNF	Primary Nonfunction	up to 12 weeks
Changes from baseline in free C2, total C2, and CH50		up to 64 weeks

Collaborators and Investigators

• Sponsor: argenx

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2024
• Primary Completion (Actual): October 16, 2025
• Study Completion (Estimated): July 31, 2026

Study Registration Dates

• First Submitted: June 8, 2023
• First Submitted That Met QC Criteria: June 8, 2023
• First Posted (Actual): June 18, 2023

Study Record Updates

• Last Update Posted (Actual): March 18, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Pathological Conditions, Signs and Symptoms; Delayed Graft Function
• Other Study ID Numbers: ARGX-117-2201; 2022-503091-89-00 (Other Identifier: CTIS number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No