Kidney Transplant RejectionPhase 3TAR:GET-1NCT03994783
Transplant Antibody-Mediated Rejection: Guiding Effective Treatments
A Phase 3 study testing Rituximab, Methylprednisolone and Intravenous Immunoglobulin in people with Kidney Transplant Rejection and Antibody-mediated Rejection, run by Imperial College London at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 5 years and older
- Conditions the study is for
- Kidney Transplant Rejection, Antibody-mediated Rejection
- What is being tested?
- Rituximab, Methylprednisolone and Intravenous Immunoglobulin
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 17 Jul 2019to 9 Jan 2023
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 5 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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):
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- 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%
Who cannot join
- 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)
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Multicentre Randomised Controlled Trial to Assess the Efficacy of Adding Rituximab to Standard of Care in Treating Acute Antibody-mediated Rejection in Kidney Transplantation
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.
Read the detailed description
Chronic antibody-mediated rejection (cAMR) is the leading cause of kidney transplant failure. Fifty percent of kidney transplant patients who develop acute antibody-mediated rejection (aAMR) will develop evidence of cAMR within 1 year of the acute rejection episode. There is currently no evidence on how to treat aAMR.
The planned research is a randomised controlled trial, which compares an acceptable and commonly used therapy, which will be referred to as "standard of care", with an additional agent, rituximab, added to the "standard of care" treatment. The participants with be randomised in a 1:1 ratio.
"Standard of care" will include optimisation of the participant's baseline anti-rejection medications and therapy to remove the antibodies which have developed against the kidney transplant, which are causing the damage. This is called plasma exchange. The participants will also receive therapy to reduce inflammation and reduce their immune response to their kidney transplant. This will be achieved using corticosteroids and intravenous immunoglobulins, respectively. These therapies have been used to treat aAMR for many decades.
The intervention arm will consist of the "standard of care" treatment, with the addition of a drug called rituximab, which will be administered in 2 separate doses. Rituximab is itself an antibody, which binds to certain cells in the body involved in antibody production, called B cells. Following the administration of rituximab, the number of B cells is reduced, which affects antibody production. Rituximab is commonly used in transplantation for this indication, as well as for other conditions.
Participants in both arms will be followed up to determine if there is a difference in the time to transplant failure and/or transplant function.
- Being tested
- Rituximab, Methylprednisolone, Intravenous Immunoglobulin, Plasma Exchange
- Keywords
- Rituximab, AMR
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
Also called Rituximab Biosimilar, Mabthera
2 intravenous infusions of rituximab or approved biosimilar given 14 days +/- 2 days apart.
Intravenous infusion of methylprednisolone
Intravenous ImmunoglobulinDrug
High dose (2 g/kg total) or Low dose (100 mg/kg, n=7)
Plasma ExchangeProcedure or surgery
Blood is removed from the patient and filtered to remove the plasma. Red and white blood cells and platelets are returned to the patient with replacement fluid.
| Study group | Role | What they receive |
|---|---|---|
| Standard of Care (SOC) | Active comparator | Intravenous Methylprednisolone (500 mg (600 mg/m2 for paediatric participants), n=3) Plasma Exchange (PEX) (60 ml/kg max 4 l (1 - 1.5 plasma volumes for paediatric participants), n=7) Intravenous Immunoglobulin (high dose: 2 g/kg total, or low dose: 100 mg/kg n=7 after each PEX, no dose adjustment for paediatric participants) Receives: Drug: Methylprednisolone; Drug: Intravenous Immunoglobulin; Procedure: Plasma Exchange |
| Standard of Care plus Rituximab (SOCR) | Experimental | Intravenous Methylprednisolone (500 mg (600 mg/m2 for paediatric participants), n=3) Plasma Exchange (PEX) (60 ml/kg max 4 l (1 - 1.5 plasma volumes for paediatric participants), n=7) Intravenous Immunoglobulin (high dose: 2 g/kg total, or low dose: 100 mg/kg n=7 after each PEX, no dose adjustment for paediatric participants) Rituximab (375 mg/m2 max 1 g (no dose adjustment for paediatric participants), n=2 14 days +/- 2 days apart) Receives: Drug: Rituximab; Drug: Methylprednisolone; Drug: Intravenous Immunoglobulin; Procedure: Plasma Exchange |
What is being measured
The primary outcome is the main question the study is designed to answer.
Allograft Survival as assessed by statistical model
Statistical model measuring allograft survival as defined as duration from the date of randomisation to the date of eGFR ≤15 mL/min/1.72 m2 (where the eGFR measurement is not due to an acute reversible cause, as determined by the PI, or a follow-up consecutive eGFR measurement of ≤15 mL/min/1.72 m2 is recorded (where the first date is recorded as the date of failure)), or the date of renal replacement therapy (date of starting maintenance dialysis dependency, retransplantation etc), whichever occurs first.
Measured: 4 years
Secondary outcomes (9)
Serum creatinine as assessed by blood test
Serum creatinine is an allograft function. Change in serum creatinine from baseline at 1, 3, 6 and 12 months post-randomisation and then annually until 4 years
Measured: 1, 3, 6 and 12 months, 2, 3 and 4 years
Estimated glomerular filtration rate (eGFR) as assessed by blood test
eGFR is an allograft function. Change in eGFR from baseline at 1, 3, 6 and 12 months post-randomisation and then annually until 4 years
Measured: 1, 3, 6 and 12 months, 2, 3 and 4 years
Proteinuria as assessed by urine test
Proteinuria is an allograft function. Change in proteinuria from baseline at 1, 3, 6 and 12 months post-randomisation and then annually until 4 years. Proteinuria is a ratio between urinary protein and creatinine.
Measured: 1, 3, 6 and 12 months, 2, 3 and 4 years
Change in donor specific antibodies as assessed by blood test
Change in number of donor specific antibodies from baseline
Measured: 3 and 12 months
Change in positivity of donor specific antibodies as assessed by blood test
Change in positivity of donor specific antibodies from baseline
Measured: 3 and 12 months
Change in mean fluorescence index of donor specific antibodies as assessed by blood test
Change in mean fluorescence index of donor specific antibodies from baseline
Measured: 3 and 12 months
Incidence rate of adverse event as assessed by questionnaire
Summary tables of incidence rates for adverse event reporting of participants receiving rituximab in addition to standard of care compared to participants receiving standard of care alone
Measured: 4 years
Health-related quality of life (QoL) as assessed by EuroQoL EQ-5D-5L/EQ-5D-Y questionnaire
A QoL score is obtained according to the answers to the EQ-5D-5L/EQ-5D-Y questionnaires. The QoL score comprises of 2 numbers. The first is a 5-digit number for the EQ-5D-5L descriptive system describing the 5 dimensions asked in the questionnaire. For example 11111 indicates no problems on any of the 5 dimensions whilst 55555 indicates extreme problems on all of the 5 dimensions. The second number is the EQ-VAS (EuroQoL-Visual Analogue Scale) score. This is a value between 0 and 100 where 0 is the worst health the respondent can imagine and 100 is the best health.
Measured: 3 months, 1, 2, 3 and 4 years
Cost effectiveness economic analysis
Statistical decision model built for economic analysis of cost per quality-adjusted life year gained from perspective of the National Health Service
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2019
- Study start17 Jul 2019
- Primary completion17 Jul 2021
- Study completion9 Jan 2023
Why it stopped: Stopped at start of COVID-19 pandemic - non-feasible
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Kidney 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- Cambridge University Hospitals NHS Foundation Trust, National Institute for Health Research, United Kingdom, Kidney Cancer UK
- Responsible party
- Sponsor
- Investigators
- Michelle Willicombe, MA MRCP MD, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03994783
- Sponsor's protocol ID
- 2018-002882-20
- Other IDs
- 2018
- Acronym
- TAR:GET-1
- Status last verified
- Apr 2025
- First submitted
- 17 Jun 2019
- Last updated
- 13 Apr 2025
- 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 13 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicentre Randomised Controlled Trial to Assess the Efficacy of Adding Rituximab to Standard of Care in Treating Acute Antibody-mediated Rejection in Kidney Transplantation
- ClinicalTrials.gov ID
- NCT03994783
- Acronym / sponsor ID
- TAR:GET-1 / 2018-002882-20
- Keywords
- Rituximab, AMR
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Stopped at start of COVID-19 pandemic - non-feasible
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- Cambridge University Hospitals NHS Foundation Trust, National Institute for Health Research, United Kingdom, Kidney Cancer UK
- Study start
- 17 Jul 2019 (actual)
- Primary completion
- 17 Jul 2021 (actual)
- Study completion
- 9 Jan 2023 (actual)
- First posted
- 21 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.
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.
Detailed description
Chronic antibody-mediated rejection (cAMR) is the leading cause of kidney transplant failure. Fifty percent of kidney transplant patients who develop acute antibody-mediated rejection (aAMR) will develop evidence of cAMR within 1 year of the acute rejection episode. There is currently no evidence on how to treat aAMR.
The planned research is a randomised controlled trial, which compares an acceptable and commonly used therapy, which will be referred to as "standard of care", with an additional agent, rituximab, added to the "standard of care" treatment. The participants with be randomised in a 1:1 ratio.
"Standard of care" will include optimisation of the participant's baseline anti-rejection medications and therapy to remove the antibodies which have developed against the kidney transplant, which are causing the damage. This is called plasma exchange. The participants will also receive therapy to reduce inflammation and reduce their immune response to their kidney transplant. This will be achieved using corticosteroids and intravenous immunoglobulins, respectively. These therapies have been used to treat aAMR for many decades.
The intervention arm will consist of the "standard of care" treatment, with the addition of a drug called rituximab, which will be administered in 2 separate doses. Rituximab is itself an antibody, which binds to certain cells in the body involved in antibody production, called B cells. Following the administration of rituximab, the number of B cells is reduced, which affects antibody production. Rituximab is commonly used in transplantation for this indication, as well as for other conditions.
Participants in both arms will be followed up to determine if there is a difference in the time to transplant failure and/or transplant function.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard of Care (SOC) | Active comparator | Drug: Methylprednisolone, Drug: Intravenous Immunoglobulin, Procedure: Plasma ExchangeIntravenous Methylprednisolone (500 mg (600 mg/m2 for paediatric participants), n=3) Plasma Exchange (PEX) (60 ml/kg max 4 l (1 - 1.5 plasma volumes for paediatric participants), n=7) Intravenous Immunoglobulin (high dose: 2 g/kg total, or low dose: 100 mg/kg n=7 after each PEX, no dose adjustment for paediatric participants) |
| Standard of Care plus Rituximab (SOCR) | Experimental | Drug: Rituximab, Drug: Methylprednisolone, Drug: Intravenous Immunoglobulin, Procedure: Plasma ExchangeIntravenous Methylprednisolone (500 mg (600 mg/m2 for paediatric participants), n=3) Plasma Exchange (PEX) (60 ml/kg max 4 l (1 - 1.5 plasma volumes for paediatric participants), n=7) Intravenous Immunoglobulin (high dose: 2 g/kg total, or low dose: 100 mg/kg n=7 after each PEX, no dose adjustment for paediatric participants) Rituximab (375 mg/m2 max 1 g (no dose adjustment for paediatric participants), n=2 14 days +/- 2 days apart) |
Who may qualify
- Ages
- 5 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (16 listed)
- 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:
Key exclusion criteria (12 listed)
- 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
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 |
|---|---|---|
| RituximabAlso: Rituximab Biosimilar, Mabthera2 intravenous infusions of rituximab or approved biosimilar given 14 days +/- 2 days apart. | Drug | Standard of Care plus Rituximab (SOCR) |
| MethylprednisoloneIntravenous infusion of methylprednisolone | Drug | Standard of Care (SOC), Standard of Care plus Rituximab (SOCR) |
| Intravenous ImmunoglobulinHigh dose (2 g/kg total) or Low dose (100 mg/kg, n=7) | Drug | Standard of Care (SOC), Standard of Care plus Rituximab (SOCR) |
| Plasma ExchangeBlood is removed from the patient and filtered to remove the plasma. Red and white blood cells and platelets are returned to the patient with replacement fluid. | Procedure or surgery | Standard of Care (SOC), Standard of Care plus Rituximab (SOCR) |
Primary outcome
Allograft Survival as assessed by statistical model
Time frame: 4 years
Statistical model measuring allograft survival as defined as duration from the date of randomisation to the date of eGFR ≤15 mL/min/1.72 m2 (where the eGFR measurement is not due to an acute reversible cause, as determined by the PI, or a follow-up consecutive eGFR measurement of ≤15 mL/min/1.72 m2 is recorded (where the first date is recorded as the date of failure)), or the date of renal replacement therapy (date of starting maintenance dialysis dependency, retransplantation etc), whichever occurs first.
9 secondary outcomes
Serum creatinine as assessed by blood test
Time frame: 1, 3, 6 and 12 months, 2, 3 and 4 years
Estimated glomerular filtration rate (eGFR) as assessed by blood test
Time frame: 1, 3, 6 and 12 months, 2, 3 and 4 years
Proteinuria as assessed by urine test
Time frame: 1, 3, 6 and 12 months, 2, 3 and 4 years
Change in donor specific antibodies as assessed by blood test
Time frame: 3 and 12 months
Change in positivity of donor specific antibodies as assessed by blood test
Time frame: 3 and 12 months
Change in mean fluorescence index of donor specific antibodies as assessed by blood test
Time frame: 3 and 12 months
Incidence rate of adverse event as assessed by questionnaire
Time frame: 4 years
Health-related quality of life (QoL) as assessed by EuroQoL EQ-5D-5L/EQ-5D-Y questionnaire
Time frame: 3 months, 1, 2, 3 and 4 years
Cost effectiveness economic analysis
Time frame: 4 years
Results and safety
The study was stopped early (reason given: Stopped at start of COVID-19 pandemic - non-feasible). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2025.
- Individual participant dataSharing planned: No
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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.
Michelle Willicombe, MA MRCP MD 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 3 study testing Rituximab, Methylprednisolone and Intravenous Immunoglobulin in people with Kidney Transplant Rejection and Antibody-mediated 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 16 inclusion and 12 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: stopped early, as of the sponsor's last update on 13 Apr 2025. 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 phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Stopped at start of COVID-19 pandemic - non-feasible). Results are not available in the source record.
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?
Allograft Survival as assessed by statistical model (time frame: 4 years). 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 13 Apr 2025.