BIOtechnology Applied to Renal TRansplantation With IMmunobiogram

NCT05816486 | Completed

• 1 other identifier: BH-IMBG-TR-2021
• Study Type: observational
• Target: 443
• Locations: 5 countries
• Sites: 15

Brief Summary

Immunobiogram (IMBG) is a novel in vitro diagnostic bioassay developed by Biohope Scientific Solutions for Human Health SL, that allows to measure the pharmacodynamic response to individual immunosuppressive drugs in patients with a renal transplantation. Pharmacodynamics can complement the already available pharmacokinetic information on immunosuppressants and enable a more individualized evaluation of the immunosuppressive therapy. The aim of this study is to evaluate the association between the pharmacodynamic response to individual immunosuppressants taken by the patient measured in vitro with IMBG and the existence of signs of graft rejection in biopsies (upon indication or protocol) performed in a sample of kidney transplant patients. The main hypothesis is that a lower sensitivity to the immunosuppressive drugs taken by the patient will be associated with a higher probability of rejection.

Conditions

Kidney Transplant Failure and Rejection

Keywords

Kidney Transplant Rejection; Immunosuppression; Immune cell bioassay; Pharmacodynamics; Oportunistic infections

Outcome Measures

Primary Outcomes (1)

• Proportion of patients with BPAR in biopsies (following BANFF 2019 criteria) who present Low Sensitivity to the prescribed Immunosupressive drugs in IMBG

  Proportion of patients with BPAR (BANFF 2019 2, 3 or 4) who present Low Sensitivity to the prescribed Immunosupressive drugs in IMBG in longitudinal cohort in 1 year- Protocol Biopsies or in Indication Biopsies and in the cross sectional cohort in Indication Biopsies

  12 months in the prospective follow-up cohort.

Secondary Outcomes (9)

• Proportion of patients with impairment in renal function AND BPAR or inflammatory damage in biopsies or the presence of dnDSA in the last determination who present low sensitivity to the individual immunosuppressive drugs in IMBG

  12 months

• Proportion of patients with impairment in renal function AND BPAR or inflammatory damage in biopsies or the presence of dnDSA in the last determination who present low sensitivity to all prescribed immunosuppressive drugs in IMBG

  12 months

• Proportion of patients with therapeutical failure due to rejection who present low sensitivity to the prescribed immunosuppressive drugs in IMBG

  12 months in the prospective follow-up cohort.

• Proportion of patients with with therapeutical failure due adverse effects attributable to immunosuppression who present high sensitivity /or low sensitivity and high doses to the prescribed immunosuppressive drugs in IMBG

  12 months in the prospective follow-up cohort.

• Proportion of patients whose pre-transplant IMBG predicts the incidence of events during the patients' follow up

  12 months

Study Arms (3)

Prospective - Longitudinal

Longitudinal follow-up cohort in which all patients who are going to receive a kidney transplant and meet the selection criteria for this study cohort will be included. This cohort will be recruited at sites that routinely perform Protocol Biopsies (PB) one year after transplant. A pre-transplant and post-transplant follow-up IMBG at 3, 6, 9 and 12 months will be performed, and additional IMBG will be carried out when an indication biopsy is required due to a suspected rejection during the patients' follow-up. A protocol biopsy will be performed after one year of follow-up of the patients.

Diagnostic Test: Immunobiogram

Cross-sectional

Patients in whom an Indication Biopsy (IB) is to be performed due to suspicion of rejection. This cohort may be recruited in all sites participating in the study, including sites where annual protocol biopsies are not routinely performed. An IMBG will be performed coinciding with the IB. This cohort will include patients who have had their transplant for less than 5 years.

Diagnostic Test: Immunobiogram

Control

Patients who have received a kidney transplant or a re-transplant less than 5 years before inclusion in the study and have shown a stable clinical course after 6 months from the RT, defined as: patients without previous rejection episodes nor indication biopsies, who do not show signs of renal impairment and are dnDSA negative, without changes in immunosuppressive drugs in the last 6 weeks and without opportunistic infections in the last six months before entering in the study. An IMBG will be performed coinciding with the only visit.

Diagnostic Test: Immunobiogram

Interventions

Immunobiogram DIAGNOSTIC_TEST

This is not an interventional study. However the assay being tested on the blood samples of all enrolled participants is the Immunobiogram (IMBG). IMBG is an in vitro diagnostic immunoassay which can obtain dose-response curves that describe the inhibitory effect of each immunosuppressant on immune response cells (immunologically stimulated PBMCs) in kidney transplant patients.

Control; Cross-sectional; Prospective - Longitudinal

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

1. Prospective longitudinal cohort: all patients who are to receive a kidney transplant and meet the screening criteria for this study cohort. This cohort will be recruited in sites that routinely perform a Protocol Biopsy (PB) one year after transplant. 2. Cross-sectional cohort: patients in whom an Indication Biopsy (IB) is to be performed due to suspicion of rejection. This cohort may be recruited in all sites participating in the study and patients will be enrolled competitively. 3. Control cohort: cross-sectional cohort to include patients who have received a kidney transplant or a re-transplant less than 5 years before inclusion in the study and have shown a stable clinical course after 6 months post-transplant. An IMBG will be performed coinciding with the study visit.

You may qualify if:

• Longitudinal cohort:
• Patients \> 18 years of age.
• Candidate to receive a kidney transplant or re-transplant.
• Patients in whom a pre-transplant blood sample can be drawn that is viable for the processing of an IMBG.
• Patients who give their written informed consent to participate in the study.
• Cross-sectional cohort:
• Patients \> 18 years of age.
• Patients in whom an indication biopsy is to be performed due to suspicion of rejection.
• Patients in whom a blood sample can be drawn in a period of time less than 8 days before or after the Indication Biopsy that is viable for the processing of an IMBG.
• Patients who give their written informed consent to participate in the study.

You may not qualify if:

• Patient with a double transplant (kidney + other organ).
• Contraindication for performing a renal graft biopsy.
• Very elderly cadaver donor transplant (\>80 years of age).
• Donors in asystole II.
• Recurrent primary kidney disease in the case of primary focal and segmental hyalinosis or hemolytic-uremic syndrome.
• Active HIV, HBV or HCV infection or other severe infections (to prevent risks in the processing of samples in conventional laboratories).
• Concomitant medical conditions that may affect the patient's participation in the study.
• Control cohort:
• Patients \> 18 years of age.
• A stable course after 6 months post-transplant defined as:
• Lack of renal impairment (GFR \> 50 ml/min/1.73 m2 and proteinuria \< 300 mg/g)
• No previous rejection episodes and no graft indication biopsies
• No positive dnDSA
• No change in the active principle of immunosuppressive drugs in the last 6 weeks
• No opportunistic infections in the last 6 months

Sponsors & Collaborators

• Biohope Scientific Solutions for Human Health, S.L.: lead

Study Sites (15)

Hospital Do Rim

Brasil, Brazil

Location

University Hospital Grenoble

Grenoble, France

Location

Charité Universitätsmedizin Berlin

Berlin, Germany

Location

Universitätsklinikum Heidelberg

Heidelberg, Germany

Location

Fundació Puigvert

Barcelona, Spain

Location

Hospital Clínic de Barcelona

Barcelona, Spain

Location

Hospital del Mar

Barcelona, Spain

Location

Hospital Universitario Puerta del Mar

Cadiz, Spain

Location

Hospital Clínico San Carlos

Madrid, Spain

Location

Hospital Universitario 12 Octubre

Madrid, Spain

Location

Hospital Universitario La Paz

Madrid, Spain

Location

Hospital Universitario Puerta de Hierro

Madrid, Spain

Location

Hospital Universitario Marqués de Valdecilla

Santander, Spain

Location

Hospital Universitario Dr. Peset

Valencia, Spain

Location

Uppsala University Hospital

Uppsala, Sweden

Location

Related Publications (3)

• Portoles JM, Jimenez C, Janeiro D, Lopez-Oliva MO, Ortega-Carrion A, Blanquez D, Arribas L, Gomez C, Diez T, Pascual J, Portero I. The Immunobiogram, a Novel In Vitro Assay to Evaluate Treatment Resistance in Patients Receiving Immunosuppressive Therapy. Front Immunol. 2021 Jan 25;11:618202. doi: 10.3389/fimmu.2020.618202. eCollection 2020.

  PMID: 33569062 BACKGROUND

• Pascual J, Jimenez C, Krajewska M, Seron D, Kotton CN, Portoles J, Witzke O, Sorensen SS, Andres A, Crespo M, Paz-Artal E, Diez T, Ortega A, Portero I. The Immunobiogram, a novel in vitro diagnostic test to measure the pharmacodynamic response to immunosuppressive therapy in kidney transplant patients. Transpl Immunol. 2022 Dec;75:101711. doi: 10.1016/j.trim.2022.101711. Epub 2022 Sep 9.

  PMID: 36096417 BACKGROUND

• Pascual J, Crespo M, Portoles J, Jimenez C, Ortega-Carrion A, Diez T, Portero I. The IMBG Test for Evaluating the Pharmacodynamic Response to Immunosuppressive Therapy in Kidney Transplant Patients: Current Evidence and Future Applications. Int J Mol Sci. 2023 Mar 8;24(6):5201. doi: 10.3390/ijms24065201.

  PMID: 36982276 BACKGROUND

Related Links

• Biohope Scientific Solutions for Human Health, S.L.

Biospecimen

Retention: SAMPLES WITHOUT DNA

Renal biopsy and blood samples

MeSH Terms

Conditions

Rejection, Psychology

Condition Hierarchy (Ancestors)

Social Behavior; Behavior

Study Officials

• Isabel Portero

  Biohope Scientific Solutions for Human Health, S.L.

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2023
• First Posted: April 18, 2023
• Study Start: March 1, 2022
• Primary Completion: June 30, 2024
• Study Completion: June 30, 2024
• Last Updated: July 18, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2); ES (10); FR (1); SE (1); BR (1)