Effect of Privigen Against Graft Loss

• Status: Completed
• Trial end date: 2019-05-09
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Association ASLUMARE; CSL Behring
• Treatments: Antibodies; gamma-Globulins; Immunoglobulin G; Immunoglobulins; Immunoglobulins, Intravenous; Rho(D) Immune Globulin

Criteria

Inclusion Criteria:

1. Deceased donor kidney transplant recipients between 3 and 12 months post transplantation.

2. At least 18 years old.

3. With stable renal function assessed within 30 days before inclusion and with delta GFR (MDRD) lower than 10 ml/min (latest result versus the average of the two previous values).

4. Presence of at least one circulating HLA-DSA class I or II against HLA-A, -B, -DR, -DQ, -DP, -C (MFI ≥ 1000) as assessed by Luminex single antigen technique within 30 days before inclusion.

5. 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).

6. Able to comply with the study procedures and follow the study instructions.

7. Who have read the information sheet and signed the informed consent form.

Exclusion Criteria:

1. 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.

2. Previous episode of ABMR.

3. Previous treatment with plasmapheresis, IVIg, within 2 months prior to inclusion

3b. Previous treatment with rituximab, eculizumab or bortezomib within 1 year prior to inclusion

4. Major lesions of active antibody-mediated injury, as defined by Banff criteria, such as g + ptc >3 or chronic transplant glomerulopathy (cg>0).

5. 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.

6. History of thrombotic episodes (deep vein thrombosis, myocardial infarction, cerebrovascular accident).

7. Known allergic or other severe reactions to blood products including intolerability to previous IVIg (i.e. severe headache, hypersensitivity, intravascular hemolysis).

8. Subject with a known deficit in IgA, with antibodies against IgA. 9. Known hyperprolinemia.

10. Ongoing HIV, hepatitis C and hepatitis B infection.

11. 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.

12. Not able to comply with study procedures and treatment regimen.

13. 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).

14. Participation in any other study involving investigational products, concomitantly or within 30 days prior to entry in the study.