Prevention in Recipients With Primary IgA Nephropathy of Recurrence After Kidney Transplantation: ATG-F Versus Basiliximab as Induction Immunosuppressive Treatment

NCT02523768 | Terminated Phase 4 DMC

• 3 other identifiers: 09081432009-018189-36A100405-32
• Study Type: interventional
• Target: 117
• Locations: 1 country
• Sites: 15

Brief Summary

IgA nephropathy (IgAN) is a histologically defined glomerulonephritis (renal biopsy) by the presence of deposits immunoglobulin A (IgA) in the renal mesangium (at least 1+) by immunofluorescence. The clinic allows excluding secondary forms (10-15%). Recurrence of this condition on the renal graft is time-dependent and confirmed in 25 to 50% of 10 years post-transplant. The primary immunosuppressive induction regimens currently used in kidney transplantation are the anti-lymphocyte globulin (GAL) whose main target is human T lymphocytes (ATG, polyclonal) and monoclonal anti-CD25 antibodies (α chain of the interleukin receptor 2 in the surface of T lymphocytes). Due to their potent and prolonged immunosuppressive properties, the ATG may prevent or delay the recurrence on renal transplant. The aim of this study was to evaluate the influence of induction therapy (ATG versus Basiliximab) in the cumulative incidence at 5 years of (IgAN) recurrence after a first kidney transplant. This is a prospective, multicenter, randomized, open trial with a follow-up period of 5 years old. Patients in the ATG arm will receive 5 antilymphocyte globulin infusions Fresenius® (rabbit immunoglobulin antilymphocyte human T-Fresenius® said ATG) from Day 0 to Day + 4 post-transplant (day 0 one dose of 4mg / kg, day 1 one dose of 4mg/kg, day2 one dose of 4mgkg, day 3 one dose of 3 m/kg and day 4 and one final dose of 3 mg/kg) and the patients in the anti-CD25 arm will receive 2 doses of 20 mg of basiliximab (Simulect®) pn day 0 and day 4 after the graft. The maintenance immunosuppressive therapy is left to the discretion of the center. The primary endpoint will be the clinical and histological recurrence of IgAN defined by the presence of mesangial deposits of IgA (at least 1) by immunofluorescence on a biopsy of the graft triggered by the onset of proteinuria 1g/j and/or microalbuminuria greater than 300 mg / day.

Conditions

Glomerulonephritis; IgAN

Outcome Measures

Primary Outcomes (2)

• clinical recurrence

  onset of proteinuria 1g / j and / or microalbuminuria greater than 300 mg / day

  5 years

• histological recurrence

  histological recurrence defined by the presence of mesangial deposits of IgA (at least 1+) by immunofluorescence on a biopsy of the graft

  5 years

Study Arms (2)

ATG-F

EXPERIMENTAL

The ATG-Fresenius® is administered by slow infusion over four hours after antihistamine (2 bulbs Polaramine® IV) and intravenous methylprednisolone (minimum 30mg); it is started on day 0 prior to surgery at doses of 4 mg / kg, and then continued to day 1, day 2 to 4mg / kg, then day 3, day 4 at the dose of 3 mg / kg

Drug: ATG-F

Simulect

ACTIVE COMPARATOR

The anti CD25 (basiliximab, Simulect®) is administered intravenously before surgery of renal transplantation (Day 0 and Day + 4 (1 ampoule of 20 mg x 2 times).

Drug: Simulect

Interventions

ATG-F DRUG

ATG-F

Simulect DRUG

Simulect

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Free, informed, express and written.
• Diagnosis of native kidney primary IgA glomerulonephritis biopsy-proven
• First kidney transplantation (one kidney)

You may not qualify if:

• Panel Reactive Antibody (PRA PRA global or class I or class II PRA) over 50% on a serum before transplantation
• Multi-organ graft
• Transplants using donor limits or sub-optimal: donor age ≥ 70 years, donors in the study BIGRAS or taken heart beating donors (tested on computer infusion) or other restriction factors
• IgA glomerulonephritis secondary to HSP (Henoch-Schonlein purpura) or Systemic Lupus Erythematosus (SLE) or alcoholic cirrhosis
• History of cancer older than 5 years or with advanced cancer, but except for non-recurrent skin cancers
• Infectious diseases scalable: tuberculosis, HIV, Hepatitis B virus or Hepatitis C virus infection with viral replication and / or chronic hepatitis
• Allergy to rabbit proteins
• Severe thrombocytopenia (\<50,000 platelets/ul)
• Bacterial infection, viral and fungal uncontrolled therapeutically
• Pregnancy or lactation

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Saint Etienne: lead

Study Sites (15)

CHU de BESANCON

Besançon, 25000, France

Location

CHU de BORDEAUX

Bordeaux, 33000, France

Location

Chu Kremlin Bicetre

Le Kremlin-Bicêtre, 94275, France

Location

Hopital Edouard HERRIOT

Lyon, 69000, France

Location

CHU de MONTPELLIER

Montpellier, 34000, France

Location

CHU de NANCY

Nancy, 54000, France

Location

CHU de NANTES

Nantes, 44000, France

Location

CHU de NICE

Nice, 06000, France

Location

Hopital Pitie Salpetriere

Paris, 75013, France

Location

Hopital Tenon

Paris, 75970, France

Location

Hopital LYON Sud

Pierre-Bénite, 69310, France

Location

CHU de SAINT-ETIENNE

Saint-Etienne, 42000, France

Location

CHU de STRASBOURG

Strasbourg, 67000, France

Location

CHU de TOULOUSE

Toulouse, 31000, France

Location

CHRU de TOURS

Tours, 37000, France

Location

MeSH Terms

Conditions

Glomerulonephritis

Interventions

Basiliximab

Condition Hierarchy (Ancestors)

Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Francois BERTHOUX, MD PhD

  CHU de SAINT-ETIENNE

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2015
• First Posted: August 14, 2015
• Study Start: January 8, 2011
• Primary Completion: January 24, 2020
• Study Completion: February 24, 2020
• Last Updated: January 20, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (15)