A Phase 2, Pilot Study to Assess the Safety and Efficacy of Fostamatinib in the Treatment Chronic Active Antibody Mediated Rejection in Renal Transplantation - Fostamatinib in the treatment Chronic Antibody Mediated Rejection v1.0

Imperial College London0 sites10 target enrollmentJune 18, 2019

ConditionsChronic active antibody mediated rejection of renal transplants 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]

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Chronic active antibody mediated rejection of renal transplants
Sponsor: Imperial College London
Enrollment: 10
Status: Active, not recruiting
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Outcomes Similar Trials

Overview

Brief Summary

No summary available.

Registry

who.int

Start Date

June 18, 2019

End Date

TBD

Last Updated

5 years ago

Study Type

Interventional clinical trial of medicinal product

Sex

All

Investigators

Sponsor

Imperial College London

Eligibility Criteria

Inclusion Criteria

•1\.Signed informed consent prior to any study specific screening procedures.
•2\.Male or female, at least 18 years of age.
•3\.Females must be either post\-menopausal (defined as no menses for 12 months without an alternative medical cause), surgically sterile (hysterectomy, bilateral salpingectomy or bilateral oophorectomy), or, if of child\-bearing potential, must not be pregnant or lactating. If sexually active, must agree to use a highly effective methods of birth control, which include: combined (estrogen and progestogen containing) hormonal contraception via the oral, intravaginal or transdermal route, progestogen only hormonal contraception via the oral, injectable or implantable route, an intrauterine device (IUD), an intrauterine hormone releasing system (IUS), bilateral tubal occlusion, vasectomised partner or sexual abstinence throughout the duration of the trial and for 30 days following the last dose. In males, there are no restrictions on sex or sperm donation during the study. This is based on a study which found that extremely low amounts of fostamatinib were present in human semen of healthy male volunteers who took the drug. In addition, animal studies have found that fostamatinib does not affect sperm. There are also no restrictions on males impregnating females during the course of the study.
•4\.Patients must be established on tacrolimus maintenance immunosuppression
•5\.A pre\-study renal biopsy obtained within 3 months prior to Screening (Visit 1\) will be reviewed by a renal pathologist to ensure subjects meet the following Banff histologic entry criteria:
•If C4d positive: Microcirculation inflammation score (g\+ptc) \=1
•If C4d negative: Microcirculation inflammation score (g\+ptc) \=2
•Chronic glomerulopathy (cg) score \=1b
•Chronic tubulo\-interstitial scarring \=30%
•Glomerular global obsolescence \=50%

Exclusion Criteria

•1\.Co\-existing Banff Category 4 T\-cell mediated rejection.
•2\.History of or active, clinically significant, respiratory, gastrointestinal (including pancreatitis), hepatic, neurological, psychiatric, musculoskeletal, genitourinary, dermatological, or other disorder that, in the Investigator’s opinion, could affect the conduct of the study or the absorption, metabolism or excretion of the study drug.
•3\.Have had any major cardiovascular event within the 180 days prior to randomisation, including but not limited to: myocardial infarction, unstable angina, cerebrovascular accident, pulmonary embolism, or New York Heart Association Class III or IV heart failure.
•4\.An absolute neutrophil count of \< 1,500/µL, Hgb \< 9 g/L, ALT or AST of \> 1\.5x ULN, total bilirubin \> 2\.0 mg/dL at Baseline (Visit 2\).
•5\.Acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea) at Baseline (Visit 2\). The subject may be reassessed after full recovery from the acute gastrointestinal illness.
•6\.Co\-existing BK nephropathy or pyelonephritis on screening biopsy.
•7\.Active bacterial, viral or parasitic infections, including tuberculosis. Where CMV viral infection is defined as replicating DNA \=3000 copies/ml and EBV viral infection is defined as replicating DNA \=10000 copies/ml.
•8\.Evidence of active or previous invasive fungal infection.
•9\.Positive serologic tests suggestive of active hepatitis B or hepatitis C or hepatitis E(subjects may be included if confirmed hepatitis C recombinant immunoblot assay negative or hepatitis C virus RNA negative \[qualitative]) or hepatitis E virus RNA negative by PCR), or subjects with suspected human immunodeficiency virus (HIV).
•10\.Have active malignancy.