Multicenter, Randomized Study to Evaluate the Efficacy of Individualization of Immunological Risk Based on Selective Biomarkers (Hla Epleth Disparity and Ifn-Γ Elispot) to Optimize Immunosuppressive Treatment in Living Donor Kidney Transplant Patients (Bioimmun)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacio Hospital Universitari Vall D’Hebron Institut De Recerca

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Phenomena and Processes [G] - Immune system processes [G12]

Decision date (initial)

2025-01-30

Transition trial

Yes

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2025-520884-42-00

EudraCT number

2017-002293-39

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To determine the effect of individualizing immunosuppressive therapy based on baseline immunologic risk stratification according to 2 biomarkers (ELISPOT IFN-γ d-sp and HLA-enhanced mismatch), on a composite endpoint of loss of renal function, incidence of biopsy-confirmed clinical acute rejection (BPAR), and development of dnDSA at 2 years of follow-up in patients receiving kidney transplants from living donors compared with patients followed according to a standard, non-individualized immunosuppressive regimen.

Secondary objectives 1

1. To evaluate whether individualized stratification of immunological risk and therapeutic optimization reduces patient mortality, renal graft loss, development of subclinical and chronic rejection advised on protocol biopsies at 3 and 24 months, opportunistic infections, treatment-derived metabolic disorders (diabetes mellitus, dyslipidemia and hypertension) and malignancy (cutaneous and non-cutaneous cancer) at 2 years of follow-up, as well as the savings in economic costs that this entails. In addition, changes in the allogeneic d-sp response over the 2 years of follow-up (dnDSA, ELISPOT IFN-γ d-sp, cytokines CXCL9/CXCL10 in urine), the transcriptional profile of rejection risk according to the kidney solid-organ rejection test (kSORT) and the cellular antiviral response against CMV, EBV and VBK viruses will be evaluated.

Conditions and MedDRA coding

Kidney Transplant

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Adult men and women (≥ 18 years)
2. Recipients of a first kidney transplant from a living donor who is HLA-incompatible (at least 1 HLA mismatch at any antigen level).
3. AB0 compatible transplant
4. Patients with a calculated PRA <= 75% by solid phase technique and absence of current or historical class I and class II donor-specific anti-HLA antibodies (DSA).
5. Patients who agree to participate in the trial by signing the Informed Consent specific to this study.
6. Females of Childbearing Potential must use highly reliable methods of contraception (Pearl-Index < 1) to prevent pregnancy throughout the duration of the study and for 6 weeks following completion of treatment with Mycophenolate Mofetil (MMF). Females of Childbearing Potential include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or who is not postmenopausal (defined as amenorrhea ≥ 12 consecutive months, or women who are receiving hormone replacement therapy with a documented follicular-stimulating hormone (FSH) level > 35 mlU/ml). Women of Childbearing Potential must have a negative pregnancy test performed within 72 hours prior to the start of the trial.
7. Sexually active men (including vasectomized men) receiving MMF therapy must agree to use barrier methods of contraception during treatment with MMF and for 90 days thereafter. Partners of childbearing potential of these patients should use a reliable method of contraception during the same period to minimize the risk of pregnancy.
8. Patients must agree not to donate blood during treatment with MMF and for 6 weeks afterward. Men must not donate sperm during treatment with MMF and for 90 days after completion of treatment.

Exclusion criteria 17

1. Patients with a calculated PRA >75% by solid phase technique and/or the presence of current or historical donor-specific anti-HLA antibodies (DSA) of class I and class II.
2. Positive Cross Match result
3. Patients who receive a graft from a cadaver donor.
4. HLA-identical patients
5. Patients who have undergone a previous solid organ transplant (including kidney transplant) or who will receive another concomitant solid organ transplant.
6. Patients with any of the following underlying renal diseases: a. Primary focal segmental glomerular sclerosis b. Atypical Hemolytic Uremic Syndrome (aHUS) / Thrombotic Thrombocytopenic Purpura Syndrome.
7. Patients with active Hepatitis B virus (HBV) infection and/or active Hepatitis C virus infection (positive PCR result) at the time of transplant.
8. Patients with known Human Immunodeficiency Virus (HIV) infection.
9. Patients with active systemic infection requiring continued administration of antibiotics.
10. Patients with any neoplasia except localized skin cancer and who are receiving appropriate treatment.
11. Patients with severe anemia (hemoglobin <6 g/dl), leukopenia (WBC <2500/mm3) and/or thrombocytopenia (platelets <80,000/mm3).
12. Hemodynamically unstable patients even if they have hemoglobin levels >6 g/dl.
13. Patients with intestinal pathology or severe diarrhea that may decrease absorption according to medical criteria.
14. Patients with known hypersensitivity to any of the drugs used in this study.
15. Patients who have received any investigational drug in the 30 days prior to inclusion in this study.
16. Potentially Childbearing Women who do not agree to use reliable contraceptive measures during the trial, who are pregnant, breastfeeding, or who have a positive pregnancy test at the time of inclusion in the study.
17. Patients who are legally detained in an official institution.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Composite variable evaluated at 2 years of follow-up as a proportion of patients meeting any of the following criteria: loss of renal function, incidence of biopsy-confirmed clinical acute rejection (BPAR), and development of dnDSA.

Secondary endpoints 10

1. Mortality from any cause at 24 months
2. Kidney graft loss at 24 months
3. Incidence and severity of subclinical and chronic rejection (according to protocol biopsies at 3 and 24 months)
4. Incidence of opportunistic infections at 24 months
5. Incidence of treatment-related metabolic disorders (diabetes mellitus, dyslipidemia, and hypertension) at 24 months f- Incidence of cardiovascular events at 24 months
6. Incidence of malignancy (cutaneous and noncutaneous cancer) at 24 months
7. Proportion of patients maintaining treatment according to protocol at the end of the trial
8. Changes in immune response at 24 months according to biomarkers: - allogeneic response (dn-DSA, ELISPOT IFN-γ d-sp, Memory B cell Elispot, urine cytokines CXCL9 and CXCL10) - transcriptional profile in blood of rejection risk according to the kSORT test - antiviral cellular response against CMV, EBV, VBK viruses; NKG2
9. Study of economic cost and study of adherence to treatment (using mobile Health application).
10. Serious adverse reactions (serious adverse events with a possible causal relationship with immunosuppressive treatment).

Investigational products

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

Test 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacio Hospital Universitari Vall D’Hebron Institut De Recerca

Sponsor organisation

Fundacio Hospital Universitari Vall D’Hebron Institut De Recerca

Address

Passeig De La Vall D'Hebron 119-129

City

Barcelona

Postcode

08035

Country

Spain

Scientific contact point

Organisation

Fundacio Hospital Universitari Vall D’Hebron Institut De Recerca

Contact name

Oriol Bestard

Public contact point

Organisation

Fundacio Hospital Universitari Vall D’Hebron Institut De Recerca

Contact name

Oriol Bestard

Locations

1 EU/EEA country · 6 investigational sites

By country

Investigational sites

Results and documents

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

Documents 4 files

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

Application history

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