Fostamatinib in the Treatment of Chronic Active Antibody Mediated Rejection

NCT03991780 | Active Not Recruiting Phase 1 DMC

• 2 other identifiers: 18HH44882018-000027-14
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Renal Transplant Rejection

Keywords

Renal transplant rejection; donor specific antibody; antibody mediated rejection; spleen tyrosine kinase; fostamatinib

Outcome Measures

Primary Outcomes (1)

• Histological changes of antibody mediated rejection assessed by a histopathologist

  Pre treatment and Post treatment renal transplant biopsies will be scored by a histopathologist

  6 months

Secondary Outcomes (3)

• Concentration of Protein in urine

  6 months and 12 months

• eGFR ( Estimated Glomerular Filtration Rate) assessed by a blood test

  6 months and 12 months

• Donor specific antibody levels

  6 months and 12 months

Study Arms (1)

Fostamatinib

EXPERIMENTAL

All patients will be given treatment with Fostamatinib. The initial treatment dose will be 100mg of Fostamatinib (tablet taken orally) twice daily for 8 weeks. If after 8 weeks the participant has not experienced any side effects and are tolerant of this dose, then the dose will increase to 150mg twice daily. This dose will continue for the duration of the study.

Drug: Fostamatinib

Interventions

Fostamatinib DRUG

All patients will be given treatment with Fostamatinib. The initial treatment dose will be 100mg of Fostamatinib twice daily for 8 weeks. If after 8 weeks the participant has not experienced any side effects and are tolerant of this dose, then the dose will increase to 150mg twice daily. This dose will continue for the duration of the study.

Also known as: Spleen Tyrosine Kinase Inhibitor, TAVALISSE

Fostamatinib

Eligibility Criteria

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

You may qualify if:

• Signed informed consent prior to any study specific screening procedures.
• Male or female, at least 18 years of age
• Females must be either post-menopausal, surgically sterile (hysterectomy, bilateral salpingectomy or bilateral oophorectomy), or, if of child-bearing potential, must not be pregnant or lactating.
• Patients must be established on tacrolimus maintenance immunosuppression
• A pre-study renal biopsy obtained within 3 months prior to Baseline (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 or significant Peritubular Capillary Basement Membrane Multilayering (PTCBML) Chronic tubulo-interstitial scarring ≤50% Glomerular global obsolescence ≤50% Sample must contain at least 7 glomeruli and 1 artery

You may not qualify if:

• In the Investigator's opinion, understand the duration of the study (up to 52 weeks), including the requirements for renal biopsies, and has the ability to understand the nature of the study and any hazards of participation and to communicate satisfactorily with the Investigator.
• Co-existing Banff Category 4 T-cell mediated rejection
• 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.
• 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.
• 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 1).
• Acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea) at Baseline (Visit
• ). The subject may be reassessed after full recovery from the acute gastrointestinal illness.
• Co-existing BK nephropathy or pyelonephritis on screening biopsy.
• 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.
• Evidence of active or previous invasive fungal infection.
• 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).
• Have active malignancy.
• Currently enrolled in an investigational drug or device study or have used an investigational drug or device within 30 days or 5 half-lives (whichever is longer) from Baseline (Visit 1).
• Are unable or unwilling to follow instructions, including participation in all study assessments and visits.
• Have a history of alcohol or substance abuse that, in the judgment of the Investigator, may impair or risk the subject's full participation in the study.

Sponsors & Collaborators

• Imperial College London: lead

Study Sites (1)

Imperial College NHS Healthcare Trust

London, W12 0HS, United Kingdom

Location

MeSH Terms

Interventions

fostamatinib

Study Officials

• Frederick Tam, MBBChir

  Imperial College London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Open label
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single centre, not randomised, open label

Study Record Dates

• First Submitted: May 1, 2019
• First Posted: June 19, 2019
• Study Start: May 8, 2019
• Primary Completion: April 5, 2023
• Study Completion: October 15, 2025
• Last Updated: November 25, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)