Renal Transplant RejectionPhase 1/2FOSTAMRNCT03991780
Fostamatinib in the Treatment of Chronic Active Antibody Mediated Rejection
A Phase 1/2 study testing Fostamatinib in people with Renal Transplant Rejection, run by Imperial College London at 1 site in United Kingdom.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Renal Transplant Rejection
- What is being tested?
- Fostamatinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 8 May 2019to 15 Oct 2025
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- Otherwise in stable health as determined by the Investigator based on medical history and laboratory tests during the screening period. See Exclusion Criteria for specific exclusions.
- 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.
Who cannot join
- 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
- 1). The subject may be reassessed after full recovery from the acute gastrointestinal illness.
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- 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.
- Have a condition or be in a situation that the Investigator feels may put the subject at significant risk, may confound the study results, or may interfere significantly with the subject's participation in the study.
- Have a known allergy and/or sensitivity to the study drug or its excipients.
- Pregnancy or for women that are sexually active, unable to take highly effective contraception (please see inclusion criteria 3 for more information regarding what classifies as a highly effective contraception method)
- Women who are breastfeeding
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Imperial College NHS Healthcare Trust
London, W12 0HS
About this study
Official title: 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
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
Read the detailed description
The commonest cause of renal transplant failure worldwide is rejection, a process whereby the recipient's immune system recognises the transplant kidney as foreign and attacks it. One common form of rejection is due to the recipient developing antibodies against their kidney transplant. Spleen tyrosine kinase is a molecule present in immune cells which is important in the process of antibody mediated damage. Fostamatinib is a drug which inhibits spleen tyrosine kinase.
This clinical trial will recruit 10 patients who have a renal transplant and a diagnosis of antibody mediated rejection. Patients will be given Fostamatinib for 12 months and will undergo a renal biopsy at 6 months and at a 12 months in order to determine whether the histological signs of antibody mediated rejection have either improved or not progressed.
- Conditions
- Renal Transplant Rejection
- Being tested
- Fostamatinib
- Keywords
- Renal transplant rejection, donor specific antibody, antibody mediated rejection, spleen tyrosine kinase, fostamatinib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FostamatinibDrug
Also called Spleen Tyrosine Kinase Inhibitor, TAVALISSE
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Fostamatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Histological changes of antibody mediated rejection assessed by a histopathologist
Pre treatment and Post treatment renal transplant biopsies will be scored by a histopathologist
Measured: 6 months
Secondary outcomes (3)
Concentration of Protein in urine
The Level of proteinuria will be assessed by collected a urine samples which will be sent to the clinical laboratory and the protein/creatinine ratio will be calculated. The normal value of the protein/creatinine ratio should be <10, anything higher than this indicated that the kidney is "leaky" and functioning abnormally. Levels of proteinuria will be compared pre and post treatment
Measured: 6 months and 12 months
eGFR ( Estimated Glomerular Filtration Rate) assessed by a blood test
GFR is Glomerular Filtration Rate and it is a key indicator of renal function. The normal eGFR is 60 or more. If your eGFR is less than 60 for three months or more, your kidneys may not be working well. Th eGFR of participants will be compared pre and post treatment.
Measured: 6 months and 12 months
Donor specific antibody levels
The mean fluorescence intensity (MFI) of donor specific antibody present will be compared pre and post treatment. Each participant will have their Donor specific antibodies measured at baseline pre treatment, this specific antibody or antibodies will be re-measured post treatment and the level (MFI) of the antibody/antibodies will be compared to pre treatment levels.
Measured: 6 months and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jun 2019
- Study start8 May 2019
- Primary completion5 Apr 2023
- Study completion15 Oct 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Renal Transplant RejectionStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single centre, not randomised, open label
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Frederick Tam, MBBChir, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03991780
- Sponsor's protocol ID
- 18HH4488
- Other IDs
- 2018-000027-14, 2018
- Acronym
- FOSTAMR
- Status last verified
- Nov 2024
- First submitted
- 1 May 2019
- Last updated
- 25 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03991780
- Acronym / sponsor ID
- FOSTAMR / 18HH4488
- Conditions
- Renal Transplant Rejection
- Keywords
- Renal transplant rejection, donor specific antibody, antibody mediated rejection, spleen tyrosine kinase, fostamatinib
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Study start
- 8 May 2019 (actual)
- Primary completion
- 5 Apr 2023 (actual)
- Study completion
- 15 Oct 2025 (estimated)
- First posted
- 19 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
The commonest cause of renal transplant failure worldwide is rejection, a process whereby the recipient's immune system recognises the transplant kidney as foreign and attacks it. One common form of rejection is due to the recipient developing antibodies against their kidney transplant. Spleen tyrosine kinase is a molecule present in immune cells which is important in the process of antibody mediated damage. Fostamatinib is a drug which inhibits spleen tyrosine kinase.
This clinical trial will recruit 10 patients who have a renal transplant and a diagnosis of antibody mediated rejection. Patients will be given Fostamatinib for 12 months and will undergo a renal biopsy at 6 months and at a 12 months in order to determine whether the histological signs of antibody mediated rejection have either improved or not progressed.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single centre, not randomised, open label
| Arm | Type | Receives |
|---|---|---|
| Fostamatinib | Experimental | Drug: FostamatinibAll 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FostamatinibAlso: Spleen Tyrosine Kinase Inhibitor, TAVALISSEAll 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. | Drug | Fostamatinib |
Primary outcome
Histological changes of antibody mediated rejection assessed by a histopathologist
Time frame: 6 months
Pre treatment and Post treatment renal transplant biopsies will be scored by a histopathologist
3 secondary outcomes
Concentration of Protein in urine
Time frame: 6 months and 12 months
eGFR ( Estimated Glomerular Filtration Rate) assessed by a blood test
Time frame: 6 months and 12 months
Donor specific antibody levels
Time frame: 6 months and 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2024.
- Individual participant dataSharing planned: No
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Non-Invasive Monitoring of Pediatric Kidney Transplant Recipients and Immunosuppression Personalization: an Open-labeled Multicenter Randomized Controlled Study
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(TNX-1500) in Kidney Transplant Recipients
Kidney Transplant, Kidney Transplant Failure and Rejection
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A Study to Learn About the Effects of Felzartamab Infusions in Adults With Kidney Transplants Who Have Late Isolated Microvascular Inflammation
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Not yet recruitingObservational study
Assessment of Perceived Stress in an Observational Study Evaluating a Biopsy-sparing Surveillance Strategy in Kidney Transplant Recipients With Blood and Urinary Biomarkers Predictive of the Absence of Rejection
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Frederick Tam, MBBChir principal investigator
Imperial College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Fostamatinib in people with Renal Transplant Rejection, run by Imperial College London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 25 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Histological changes of antibody mediated rejection assessed by a histopathologist (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Nov 2024.