Effect of Privigen Against Graft Loss

NCT02374736 | Completed Phase 3

• 2 other identifiers: P1405012014-003707-30
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

The principal objective of this pilot study is to determine whether the progression of chronic antibody-mediated rejection (ABMR) could be minimized by the post-transplant administration of high dose of Intravenous Immunoglobulins (IVIg). We test the hypothesis that repetitive IVIg administration reduces or stabilize the progressive loss of transplant function and the evolution to chronic ABMR in stable kidney transplant patients with HLA-DSA developed post-transplantion (de novo HLA-DSA) and concomitant humoral graft injury.

Conditions

Kidney Transplantation

Keywords

recipients; Subclinical Antibody-mediated rejection (ABMR); Intravenous immunoglobulins (IVIg); Donor-specific antibodies (DSA)

Outcome Measures

Primary Outcomes (2)

• Graft function: estimation of change from baseline Glomerular Filtration Rate (GFR) using MDRD

  using Modification of Diet in Renal Disease (MDRD) equation at M6

  at months 6

• Graft function: estimation of change from baseline Glomerular Filtration Rate (GFR) using MDRD

  using Modification of Diet in Renal Disease (MDRD) equation at M12

  at months 12

Secondary Outcomes (5)

• Change of proteinuria from baseline

  months 6 and months 12

• Change of HLA-DSA from baseline

  months 6 and months 12

• Change of Histological characteristics from baseline

  at months 6

• IgG dosage

  up to months 6

• Infectious events reported during the study period

  up to months 12

Study Arms (1)

Human normal immunoglobulin G (IgG > 98 % purity)

EXPERIMENTAL

All subjects will be treated for 6 months. The treatment will start the day of inclusion (M0). Privigen will be given as 2 g/kg for 2 days/month. The maximum daily dose authorized will be 80g. The infusion rates are the recommended rates for Privigen in other indications and are in line with the market authorization for Privigen: * Infusions should start at a rate of 0.5 mg/kg/min (0.005 mL/kg/min; 0.3 mL/kg/h; 30 mg/kg/h). If well tolerated within 30 min, the rate can be increased in a first step to 1.0 mg/kg/min (0.01 mL/kg/min; 0.6 mL/kg/h; 60 mg/kg/h) for another 30 min. * If well tolerated, a stepwise increase to a maximum of 8 mg/kg/min (0.08 mL/kg/min; 4.8 mL/kg/h; 480 mg/kg/h) is allowed at the discretion of the investigator.

Drug: Privigen (Human normal immunoglobulin G (IgG > 98 % purity))

Interventions

Privigen (Human normal immunoglobulin G (IgG > 98 % purity)) DRUG

Privigen (CSL Behring AG, Bern, Switzerland) 10% liquid human IgG for intravenous administration, 2 g/kg, given as 2 g/kg for 2 days/month for 6 months (maximum dose: 80 g/day). Privigen will be provided in vials containing 10 g IgG in 100 mL.

Human normal immunoglobulin G (IgG > 98 % purity)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Deceased donor kidney transplant recipients between 3 and 12 months post transplantation.
• At least 18 years old.
• With histological markers of active antibody-mediated injury as defined by the microcirculation inflammation score (g, ptc scores defined by current Banff criteria) on protocol biopsies performed at M3 or M12 post-transplantation, or if required between three and twelve months post transplantation (1 ≤ g+ptc ≤ 3).
• Able to comply with the study procedures and follow the study instructions.
• Who have read the information sheet and signed the informed consent form.

You may not qualify if:

• Acute renal dysfunction at the time of enrolment: decrease of GFR higher or equal to 10 ml/min (latest result versus the average of the two previous values), or 20% increase of serum creatinine.
• Previous episode of ABMR.
• \. Major lesions of active antibody-mediated injury, as defined by Banff criteria, such as g + ptc \>3 or chronic transplant glomerulopathy (cg\>0).
• \. History of cardiac insufficiency (New York Heart Association \[NYHA\] III/IV), cardiomyopathy, significant cardiac dysrhythmia requiring treatment, unstable or advanced ischemic heart disease, congestive heart failure or severe hypertension.
• \. History of thrombotic episodes (deep vein thrombosis, myocardial infarction, cerebrovascular accident).
• \. Known allergic or other severe reactions to blood products including intolerability to previous IVIg (i.e. severe headache, hypersensitivity, intravascular hemolysis).
• \. Subject with a known deficit in IgA, with antibodies against IgA. 9. Known hyperprolinemia.
• \. Ongoing HIV, hepatitis C and hepatitis B infection.
• \. Any condition (including alcohol, drug or medication abuse) that is likely to interfere with evaluation of the study product or satisfactory conduct of the study.
• \. Not able to comply with study procedures and treatment regimen.
• \. Pregnant or lactating women or women of childbearing potential without effective method of contraception (oral contraceptive pill, intra-uterine contraceptive device, contraceptive implant or condom).
• \. Participation in any other study involving investigational products, concomitantly or within 30 days prior to entry in the study.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• CSL Behring: collaborator
• Association ASLUMARE: collaborator

Study Sites (1)

Service de Néphrologie et transplantation rénale - HU Saint-Louis

Paris, Île-de-France Region, 75010, France

Location

MeSH Terms

Interventions

Immunoglobulins, Intravenous; Immunoglobulin G

Intervention Hierarchy (Ancestors)

Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Denis GLOTZ, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 20, 2015
• First Posted: March 2, 2015
• Study Start: February 5, 2016
• Primary Completion: March 9, 2018
• Study Completion: May 9, 2019
• Last Updated: March 9, 2021

Record last verified: 2021-02

Locations

FR (1)