Personalized dosing of immunosuppression after kidney transplantation by measuring the immune system functionality

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medical University Of Vienna

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

23 Aug 2022 → 26 May 2025

Decision date (initial)

2022-07-01

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

European Union Horizon 2020 Framework Programme for Research and Innovation

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

To demonstrate non-inferiority with respect to safety, tolerability and preliminary efficacy of TTV-guided immunosuppression compared to standard TAC dosing in stable adult kidney transplant patients with
low immunological risk in the first year after transplantation.

Secondary objectives 1

1. Assessment of TTV-guided immunosuppression in stable adult kidney transplant patients with low immunological risk in the first year after transplantation according to secondary endpoints.

Conditions and MedDRA coding

Post Kidney transplantation

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Recipient of a kidney allograft
2. Adult (≥18 years of age)
3. Post day 93 following transplantation
4. TAC-based immunosuppression
5. Standard target TAC trough level (as defined by local centre; might exclude patients with e.g. a lung transplantation or de novo DSA or thrombotic microangiopathy [TMA] if the centre applies non-standard TAC trough levels in these circumstances)
6. Written informed consent

Exclusion criteria 25

1. HLA incompatible transplantation (as defined by local centre; e.g. preformed DSA and/or crossmatch conversion)
2. Combined transplantation
3. History of HIV or active Hep B/C infection
4. No standard immunosuppression according to local centre definition; e.g. necessity of significant additional long term im- munosuppression or immune modulation (e.g. disease modify- ing agents in autoimmune disease or immune modulators for cancer)
5. Donor history of HIV or Hep B/C infection
6. TTV load always below 4.6 log10 c/mL during screening phase
7. No stable TAC trough levels achieved during screening phase (as defined by local centre)
8. Hypersensitivity to TAC or other macrolides and hypersensitivity to any excipients
9. Cyclosporine, mTor inhibitor or Co-stimulation blocker based immunosuppression.
10. Women of childbearing potential, except women who meet one of the following criteria: a) post-menopausal (12 months natural amenorrhoea) b) postoperative (6 weeks after bilateral ovarectomy with or with- out hysterectomy, bilateral salpingectomy) c) regular and correct use of a contraceptive method with an Pearl Index < 1% per year d) sexual abstinence e) vasectomy of the partner
11. Treatment with T-cell depleting drugs within 2 months before the randomization (e.g. anti-thymocyte globulin)
12. Unstable angina, cardiac decompensation with the necessity of inpatient treatment
13. Current infection or allograft rejection as defined by the primary end-point
14. Biopsy proven antibody mediated rejection (ABMR) or BK vi- rus PCR ≥104 c/ml (or corresponding U/mL) in the blood until randomisation.
15. Unstable graft function: eGFR <25 mL/min/1.73m2 (this limit might be ignored if creatinine clearance is >25 mL/min/1.73m2) or rapid and relevant eGFR decline (as defined by local centre), urinary protein/creatinine ratio >2000 mg/g, or rapid and rele- vant increase (as defined by the local centre)
16. Advanced liver failure (CHILD-Pugh score C)
17. History of malignancy other than squamous cell carcinoma or basal cell carcinoma of the skin or carcinoma in situ or ade- noma of the colon within the last 5 years unless in complete re- mission since at least 3 years
18. Leukopenia <2000/mm3 or neutropenia <1000/mm3
19. Severe tremor (as defined by local centre) due to TAC
20. ABO incompatible transplantation (as defined by local centre; e.g. relevant ABO incompatible blood group combination)
21. Inability to perform study visits at the trial centre
22. Any state that excludes adherence with the trial protocol, such as serious medical or psychiatric illness, language barrier, alcohol or illicit substance abuse or non-adherence
23. Addictions or other illnesses that do not allow the person concerned to assess the nature and extent of the clinical trial and its possible consequences
24. Simultaneous participation in another interventional clinical trial
25. Pregnant or breastfeeding women

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. A composite of one of the following: 1. Infectious disease event requiring one of the following: a) Inpatient treatment (including day-care) b) Application of anti-bacteria, fungal, viral and protozoal drugs c) Reduction of immunosuppression; SARS-CoV-2 infection (including positive antigen or PCR test) with or without COVID-19 is excluded; 2. Allograft rejection detected upon indication biopsy; 3. Death; 4. Graft loss

Secondary endpoints 15

1. Single components of the composite primary end point
2. Composite of all components of the primary end point, whereas episodes of infection and graft rejection are scored by the treat- ing medical personnel
3. Composite of all components of the primary end point, whereas infections are restricted to severe of infections (necessitating treatment in the inpatient or day-care ward) and rejections are restricted to severe rejections (excluding BL TCMR)
4. Estimated glomerular filtration rate (eGFR; current CKD EPI and MDRD abbreviated)
5. Rejection detected by protocol biopsy at month 12 post- transplantation: according to BANFF 2019 meeting report (including/excluding BL TCMR) and according to molecular microscope (MMDX)
6. de novo donor specific antibodies (DSA)
7. Plasma TTV load
8. TAC trough level and dose
9. Unchanged, increased, and decreased TAC trough target levels
10. Health related quality of live: SF-36 and MTSOSD-59R questionnaires
11. Drug adherence assessed according to paper-based assessment, MEMS® Buttons (AARDEX Group, Switzerland) on TAC blisters, BAASIS questionnaire, claimed prescriptions, psychological evaluation and TAC trough level variability
12. Adverse Events and Serious Adverse Events (AEs/SAEs)
13. Development of malignoma
14. The three in CTIS ID no. 1,2 and 3 mentioned secondary end-points including COVID-19
15. Episodes of infection due to SARS-CoV-2

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medical University Of Vienna

Sponsor organisation

Medical University Of Vienna

Address

Spitalgasse 23, Alsergrund Alsergrund

City

Vienna

Postcode

1090

Country

Austria

Scientific contact point

Organisation

Medical University Of Vienna

Contact name

Nephrology and Dialysis

Public contact point

Organisation

Medical University Of Vienna

Contact name

Nephrology and Dialysis

Locations

6 EU/EEA countries · 13 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications