An investigation into how well Mirococept (APT070) works in preventing injury to the kidney during transplant
| ISRCTN | ISRCTN14279222 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN14279222 |
| IRAS number | 1008476 |
| Secondary identifying numbers | 3639, EMPIRIKAL-2, IRAS 1008476, CPMS 63808 |
- Submission date
- 28/03/2024
- Registration date
- 04/07/2024
- Last edited
- 13/09/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Urological and Genital Diseases
Plain English summary of protocol
Background and study aims
Up to half of kidney transplant patients are diagnosed with delayed graft function (DGF). DGF is when a donor kidney does not work straight away after the transplant. The donor organ undergoes a lack of blood supply after organ retrieval. Following the reintroduction of blood flow upon transplantation the local complement system reacts. This is a set of inflammatory proteins that play a critical role in the development of DGF. Patients who develop DGF are more likely to reject the transplanted kidney. DGF can also contribute to reduced kidney transplant survival and to prolonged hospitalisation. Thus, a treatment that can help prevent DGF is important. The EMPIRIKAL-2 trial is evaluating the effect of a drug called Mirococept. The study aims to identify the best dose for the drug to help protect against DGF. Treatment of the donor kidney with Mirococept will occur before transplantation. Mirococept is retained in the donor kidney where it targets the complement system. So, the systemic impact of the drug is expected to be limited.
Who can participate?
Eligible patients aged ≥ 16 years old and over on the kidney transplant register
What does the study involve?
Recruitment will take place at NHS hospital centres in the UK. Initially, 9 participants will be recruited to assess preliminary safety. Three different doses will be tested. If successful, the enrolment of a further 144 participants will be undertaken. Allocation to one of four different treatment groups will be at random. They will receive a kidney treated with Mirococept at one of three doses or with a standard solution. There will be blinding (concealment) of treatment allocation during this stage. Participant follow-up is for 12 months after transplantation. This will be during routine clinical follow-up (no extra appointments). There will be some collection of research blood and optional tissue samples. All other tests/procedures will be as per routine care.
What are the possible benefits and risks of participating?
Mirococept may help the recovery of kidney function following a kidney transplant. However, this cannot be stated for certain until this and future studies have been completed. There may be no direct benefit from participating in this study. Still, the information gained from participation may help improve the treatment of patients with this condition in the future.
Where is the study run from?
King’s College London and Guy's Hospital
When is the study starting and how long is it expected to run for?
March 2024 to August 2026
Who is funding the study?
Medical Research Council (MRC)
Who is the main contact?
Alima Rahman, alima.rahman@gstt.nhs.uk
Contact information
Scientific, Principal Investigator
Peter Gorer Department of Immunobiology, School of Immunology & Microbial Sciences, King’s College London, 5th Floor Tower Wing, Guy's Hospital, Great Maze Pond
London
SE1 9RT
United Kingdom
| Phone | +44 (0)20 7188 8566 |
|---|---|
| theodoros.kasimatis@gstt.nhs.uk |
Public
Guy's and St Thomas' NHS Foundation Trust R&D Department, 16th Floor Tower Wing, Great Maze Pond
London
SE1 9RT
United Kingdom
| Phone | +44 (0)20 71887188 ext 56688 |
|---|---|
| alima.rahman@gstt.nhs.uk |
Study information
| Study design | Randomized placebo-controlled double-blind parallel-group study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Safety, Efficacy |
| Scientific title | A multi-centre, multi-arm, double-blind randomised placebo-controlled dose finding trial investigating the safety and Efficacy of MirococePt (APT070) In Reducing delayed graft function In the Kidney ALlograft |
| Study acronym | EMPIRIKAL-2 |
| Study objectives | Primary objective: To identify the most safe and efficacious dose of Mirococept to reduce delayed graft function (DGF) rate in deceased-donor renal transplantation so this can be taken forward in a pivotal Phase III study Secondary objectives: 1. Evaluate the efficacy of Mirococept to improve the rate of recovery in grafts with DGF or immediate graft function (IGF) independent of dialysis. 2. Determine if treatment influences renal function at 12 months (a surrogate of long-term graft outcome) and the incidence of acute rejection episodes during this time. 3. Estimate more accurately effect size, currently estimated conservatively at 20%. This will also allow the correct powering of the phase III pivotal study. |
| Ethics approval(s) |
Approved 13/05/2024, North East - Newcastle & North Tyneside 2 Research Ethics Committee (2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; +44 (0)207 104 8086, (0)207 104 8140, (0)207 104 8016; newcastlenorthtyneside2.rec@hra.nhs.uk), ref: 24/NE/0071 |
| Health condition(s) or problem(s) studied | Kidney failure |
| Intervention | Mirococept is perfused as a single dose of 60mg, 120mg, 180mg or placebo (vehicle solution), mixed with a cold storage solution to the explanted donor kidney via the renal artery(s) before transplantation. Initial Safety Run 9 participants will be enrolled into the safety run at Guy’s Hospital, assigned to one of the three treatment doses (60, 120 or 180mg) and followed up for 12 months. Participants 1-3 will receive kidneys treated with 60mg of Mirococept; participants 4-6 will receive kidneys treated with 120mg; and participants 7-9 will receive kidneys treated with 180mg. Recruitment within each dosing group will be staggered so that the interval between participants will be a minimum of 48 hours and up to two weeks, to allow a full safety assessment for each participant. In between the dosing groups, there will be a review of safety data before dose escalation to the next level. After completion of the safety run, a DMC meeting will be convened to review the safety data before progression to the randomised controlled trial is permitted. It will be considered successful if the DMC consider at least one dose can be taken forward for comparison to placebo. This will provide a go/no go gate to the main recruitment of the multi-centre randomised controlled trial (RCT). Multi-arm randomised placebo-controlled trial If safety is met, 144 participants (36 per arm) (allowing for a 10% dropout rate) will be randomised at multi-centres via an online randomisation system to one of the three treatment doses of Mirococept (60, 120 or 180mg) or placebo on a 1:1:1:1 basis, stratified by centre and donor type. 90 participants (30 per arm) will be required if 2 of the proposed doses are well-tolerated and 40 participants (20 per arm) if only one dose is well-tolerated in the safety run. Participants will be followed up for 12 months. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Dose response, Therapy |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Mirococept [MIrococept] |
| Primary outcome measure | Delayed graft function (DGF) – the requirement for dialysis during week 1 post-transplantation |
| Secondary outcome measures | 1. Functional DGF – failure of serum creatinine to decrease by at least 10% daily on 3 consecutive days in week 1 post-transplantation (excludes patients with biopsy-proven rejection or calcineurin inhibitor (CNI) toxicity in week 1 post-transplantation) 2. Number of dialysis sessions during the first 30 days post-transplantation 3. Duration of DGF 4. Mean calculated GFR (CKD-EPI) at 12 months post-transplantation 5. Mean calculated creatinine clearance (Cockcroft-Gault) at 12 months post-transplantation 6. Primary non-function – permanent lack of graft function for 3 months post-transplantation 7. AUC of serum creatinine on days 1-14 post-transplantation 8. Biopsy-proven acute rejection at 6 and 12 months post-transplantation 9. Biopsy-proven calcineurin (CNI) toxicity within 12 months post-transplantation 10. Duration of post-transplantation hospital stay 11. Number and duration of any hospital admissions during the first 12 months post-transplantation 12. 1-year graft survival (censored and uncensored for death with functioning allograft) 13. 1-year patient survival |
| Overall study start date | 26/03/2024 |
| Completion date | 13/08/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Lower age limit | 16 Years |
| Sex | Both |
| Target number of participants | 170 |
| Key inclusion criteria | 1. Male or female patients aged ≥ 16 years old and over at the date of consent 2. Registered on the kidney transplant list 3. Recipient of a deceased donor kidney only 4. Able and willing to provide written informed consent 5. Able to comply with study requirements 6. On Dialysis at the date of consent 7. Donor age > 10 years |
| Key exclusion criteria | 1. Evidence of HIV, HCV or current HBV infection at screening 2. Multi-organ transplant or a previous non-renal transplant 3. Planned ABO- or HLA-antibody-incompatible transplant or patients with delisted HLA specificities 4. Recipient of a living-donor kidney 5. Recipient of a DCD kidney Maastricht category 1 or 2 6. Paediatric-en-bloc or an adult double-renal transplant 7. Kidneys undergoing machine perfusion both ex-vivo and Normothermic Regional Perfusion (NRP) 8. Pregnant or lactating patients (females of childbearing potential with a positive serum pregnancy test at screening) 9. Female patients of childbearing potential who are not willing to use a highly effective method of contraception for at least 1-month post-transplantation to prevent pregnancy, or abstain from heterosexual activity 10. Male patients who are not willing to use an effective method of contraception (condoms), at least 1 month post-transplantation, when engaging in sexual activity with a female of childbearing potential 11. Involvement in other interventional trials from the date of consent until completion of visit week 52 12. Known hypersensitivity to Mirococept and/or its excipients 13. Receiving treatment with a systemically administered complement inhibitor |
| Date of first enrolment | 07/10/2024 |
| Date of final enrolment | 12/08/2025 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
London
SE1 9RT
United Kingdom
London
E1 1BB
United Kingdom
Tooting
London
SW17 0QT
United Kingdom
Headington
Oxford
OX3 7LE
United Kingdom
De Crespigny Park
Denmark Hill
London
SE5 8AB
United Kingdom
Canterbury
CT1 3NG
United Kingdom
Sponsor information
Hospital/treatment centre
Research & Development, Floor 16, Tower Wing, Guy’s Hospital, Great Maze Pond
London
SE1 9RT
England
United Kingdom
| Phone | +44 (0)20 7188 7188 Extension 5119 |
|---|---|
| R&D@gstt.nhs.uk | |
| Website | https://www.guysandstthomas.nhs.uk/ |
"ROR" |
https://ror.org/00j161312 |
University/education
King’s Health Partners Clinical Trials Office, Floor 16, Tower Wing, Guy’s Hospital, Great Maze Pond
London
SE1 9RT
England
United Kingdom
| Phone | +44 (0)20 7188 5732 |
|---|---|
| QM.KHPCTO@kcl.ac.uk | |
| Website | https://www.kcl.ac.uk/ |
|
"ROR" |
https://ror.org/0220mzb33 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- Medical Research Council (United Kingdom), UK Medical Research Council, MRC
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 13/08/2027 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | 1. Peer reviewed scientific journals 2. Conference presentation 3. Submission to regulatory authorities 4. Anonymised data may be shared with external collaborators for use in future ethically approved research, subject to any relevant data-sharing agreements being in place. |
| IPD sharing plan | The data-sharing plans for the current study are unknown and will be made available at a later date |
Editorial Notes
13/09/2024: The recruitment start date was changed from 23/09/2024 to 07/10/2024.
21/08/2024: The recruitment start date was changed from 21/08/2024 to 23/09/2024.
02/08/2024: Internal review.
28/03/2024: Study's existence confirmed by Health Research Authority (HRA) (UK).
