Transplant Antibody-Mediated Rejection: Guiding Effective Treatments

• Status: Active, not recruiting
• Trial end date: 2027-07-01
• Target enrollment: 0
• Participant gender: All

Summary

This trial evaluates the addition of rituximab to standard of care in the treatment of antibody-mediated rejection in kidney transplant patients. The trial will involve adults and children. Half of participants will receive standard of care (methylprednisolone, intravenous immunoglobulin and plasma exchange), while the other half will receive standard of care and rituximab.

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

Details

• Lead Sponsor: Imperial College London
• Collaborators: Cambridge Clinical Trials Unit; Cambridge University Hospitals NHS Foundation Trust; Kidney Cancer UK; National Institute for Health Research, United Kingdom
• Treatments: Antibodies; gamma-Globulins; Immunoglobulins; Immunoglobulins, Intravenous; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Rho(D) Immune Globulin; Rituximab

Criteria

Inclusion Criteria:

• Willing and able to give written informed consent by patient aged 16 years and over; or by a parent or legal guardian for patients who are under 16 years old

• 5 years old or older

• A diagnosis of acute AMR as defined by:

• The presence of ≥1 donor specific antibodies (DSA)

• An adequate renal transplant biopsy with histological features consistent with active AMR with no evidence of chronicity as defined by the Banff histological classification of allograft pathology:

• If C4d positive (2 or 3):

• v score ≥1 and/or

• g score ≥1 and/or

• thrombotic microangiopathy and/or

• ptc score ≥1

• or if co-existent cellular rejection, a g score of ≥1 OR

• If C4d negative (0 or 1):

• microcirculation inflammatory score (g + ptc) ≥2

• or if co-existing cellular rejection, a g score ≥1 and (g + ptc) ≥2 AND

• Chronic glomerulopathy (cg) score 0 or 1a

• Tubulo-interstitial fibrosis <50% and glomerular obsolescence <50%

Exclusion Criteria:

• Patients who have received an ABO incompatible transplant

• Patients who have received rituximab as part of induction or post-transplant for any other indications (e.g. recurrent focal and segmental glomerular sclerosis)

• Patients who have completed PEX treatment prior to the index biopsy on the suspicion of acute AMR in the absence of histology

• Have active infection including bacterial, viral (including CMV (cytomegalovirus) and EBV (Epstein-Barr virus)), fungal or tuberculosis, which in the investigator's opinion could affect the conduct of the trial

• Co-existing BK (BK virus) nephropathy

• Patients with hepatitis B (patients with prior exposure to hepatitis B may be enrolled at the discretion of the PI)

• Have active hepatitis C (patients may be included if a negative hepatitis C recombinant immunoblot assay is confirmed or have a negative hepatitis C virus RNA [qualitative] test)

• Have human immunodeficiency virus (HIV)

• Active malignancy, which would pose a contraindication to any of the trial interventions

• Patients with known allergy, intolerance or contraindication to treatments in the standard of care arm or rituximab as outlined in the Summaries of Product Characteristics (SmPCs)

• Clinically significant comorbidity

• Females must be either post-menopausal for at least 1 year, surgically sterile or, if of child-bearing potential, must not be pregnant or lactating. If sexually active, female participants must agree to use an acceptable method of birth control for 12 months post treatment with rituximab. Female participants must also agree not to breastfeed for 12 months post treatment with rituximab.