Treatment of Early Borderline Lesions in Low Immunological Risk Kidney Transplant Patients: a Spanish Multicenter, Randomized, Controlled Parallel-group Trial: The TRAINING Study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacion Canaria Instituto De Investigacion Sanitaria De Canarias

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Not possible to specify

Decision date (initial)

2025-01-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-519895-23-00

EudraCT number

2021-003089-11

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Diagnosis, Therapy

Know in a controlled and randomized clinical trial, carried out in low-risk patients
immunological and stable renal function, if the treatment of BL lesions, detected in the third month post-transplant,
with rabbit polyclonal antilymphocytic globulin prevents or slows the progression of
chronic histological lesions of the graft (FIAT) and the deterioration of its function compared to clinical follow-up
conventional, after two years of post-transplant follow-up.

Secondary objectives 1

1. To analyze and compare the incidence of immunological dysfunction (acute clinical and subclinical rejections) and the evolution of histological findings in the two therapeutic arms. - Know the relationship between α-klotho and clinical and subclinical acute rejection, as well as with lesions of FIAT in the two study arms.

Conditions and MedDRA coding

To analyze whether the anti-rejection treatment of borderline lesions can modify the expression and klotho levels, as well as proinflammatory cytokines that regulate klotho expression at both years post-transplant.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. Patients of both sexes, over 18 years of age without immunological risk (PRA <20% and absence of DSA), who receive a first kidney graft from a deceased donor or a living donor. b) Presence of BL injuries, which will be defined according to the Banff 2019 classification as the presence of a interstitial inflammation score (i) and tubulitis score (t) of at least 1 point (t>0; i>0), but without reaching the threshold determined for 1A rejection of the Banff'19 classification (i2,t2) and without transmural arteritis (v0), excluding isolated inflammation (t0, i>0) and isolated tubulitis (t>0, i0). c) Patients who are receiving Tacrolimus in combination with mycophenolic acid (MPA) and steroids; d) Absence of clinical or subclinical and histological immunological dysfunction before randomization; e) Absence of anti-HLA de novo DSA antibodies at the time of randomization; f) Patients who wish and who Clinical trial protocol 6 can give written informed consent to participate in the study; g) Acceptance of efficient contraception recommended by the Clinical Trial Facilitation Group in women of childbearing age during the study.

Exclusion criteria 1

1. a)Patients receiving a multi-organ transplant; b) Retransplants; c) Patients without inflammation in the protocol biopsy of the third month (i0, t0), isolated inflammation without tubulitis (t0, i>0) or isolated tubulitis no inflammation (t>0, i0); d) Cold ischemia time >30 hours; e) Patients with higher serum creatinine at 2 mg/dl or proteinuria greater than 1g/day at the time of randomization; f) Presence of significant plateletopenia (<100,000/mm3) or leukopenia (<3,000/mm3) at the time of randomization; g) Previous clinical or subclinical rejection episode (≥AI) of the Banff classification 19 before randomization; h) Presence of borderline lesions detected in a biopsy requested by clinical indication prior to the 3rd month protocol biopsy; i) Patients with infection or CMV disease in the first three months of transplant; j) Patients with BKpoliomavirus nephropathy at the time of randomization: k) Patients with recurrent glomerulonephritis or new; l) Patients who are being treated with immunosuppressive drugs other than those in the trial clinician in question; m) Patients who are positive for the human immunodeficiency virus (HIV) or with severe systemic infection, which in the opinion of the investigator requires continued therapy; n) Patients with any previous (during the last 5 years) or present malignant disease, except carcinoma basal or squamous cell excised; ñ) Pregnant or breastfeeding women.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Presence of Interstitial Fibrosis and Tubular Atrophy (FIAT) and calculated renal function of the graft with CKD-EPI at 24 months of the study in both therapeutic arms.

Secondary endpoints 1

1. Patient and graft survival.  Rate of clinical and biopsy-confirmed acute rejection, and proteinuria at 3, 6, 12 and 24 months.  Blood pressure figures and number of hypotensive agents, lipid levels and need for lipid-lowering, and weight and BMI increase.  Rate of post-transplant diabetes (PTDM) or glucose intolerance at one year and the second year of transplantation according to ADA criteria.  Adherence to immunosuppressive treatment evaluated using the Basel scale.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacion Canaria Instituto De Investigacion Sanitaria De Canarias

Sponsor organisation

Fundacion Canaria Instituto De Investigacion Sanitaria De Canarias

Address

Barranco De La Ballena S/n

City

Las Palmas De Gran Canaria

Postcode

35019

Country

Spain

Scientific contact point

Organisation

Fundacion Canaria Instituto De Investigacion Sanitaria De Canarias

Contact name

Consuelo Rodriguez

Public contact point

Organisation

Fundacion Canaria Instituto De Investigacion Sanitaria De Canarias

Contact name

Consuelo Rodriguez

Locations

1 EU/EEA country · 1 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 5 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