Transplant Antibody-mediated Rejection: Guiding Effective Treatments-1 (TAR:GET-1)

Phase 1

• Conditions: Renal Transplant antibody-mediated rejection; MedDRA version: 20.0Level: PTClassification code 10023439Term: Kidney transplant rejectionSystem Organ Class: 10021428 - Immune system disorders; Therapeutic area: Body processes [G] - Immune system processes [G12]

• Registration Number: EUCTR2018-002882-20-GB
• Lead Sponsor: Imperial College London

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-06-27
• Last Update Posted: 16 December 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 170

Inclusion Criteria

1. 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

2. Aged 5 years old or older, at the time of consent

3. A diagnosis of acute AMR as defined by:

a.The presence of =1 donor specific antibodies (DSA)
b.An adequate transplant biopsy (=7 glomeruli and =1 artery) with histological features consistent with active AMR with no evidence of chronicity as defined by the Banff histological classification of allograft pathology:
i. 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
ii. 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%

Are the trial subjects under 18? yes
Number of subjects for this age range: 20
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 130
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion Criteria

1.Patients who have received an ABO incompatible transplant

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

3.Patients who have received complete PEX treatment prior to the index biopsy on the suspicion of acute AMR in the absence of histology

4.Have active infection including bacterial, viral (including CMV and EBV), fungal or tuberculosis, which in the investigator’s opinion could affect the conduct of the study

5.Co-existing BK nephropathy

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

7.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)

8.Active malignancy

9.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)

10.Clinically significant comorbidity

11. 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 rituximab treatment. Female participants must also agree not to breastfeed for 12 months post rituximab treatment.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified