INduction in Sensitized kidney Transplant recipients without pre-Existing donor-specific AntiboDies: a randomized multicentre trial between a lymphocyte depleting and basiliximab (INSTEAD)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Regional Universitaire De Tours

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Pathological Conditions, Signs and Symptoms [C23]

Trial duration

7 Nov 2023 → ongoing

Decision date (initial)

2023-06-30

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

DGOS

External identifiers

EU CT number

2022-502007-30-00

ClinicalTrials.gov

NCT05385432

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

Demonstrate that rATG is more efficient than basiliximab to prevent biopsy-proven acute rejection (BPAR) during the first post-transplantation year in sensitized KTR without pre-existing DSAs

Secondary objectives 8

1. Demonstrate that rATG is more efficient than basiliximab to prevent BPAR at year 3
2. Demonstrate that rATG is more efficient than basiliximab for composite criteria including BPAR, death and graft loss at year 3
3. Compare the incidence of T cell mediated rejection (TCMR) and antibody-mediated rejection (ABMR) in rATG and basiliximab groups at year 1 and 3
4. Compare the incidence of de novo DSA in rATG and basiliximab groups at year 1 and 3
5. Compare the incidence of cytomegalovirus (CMV) and BK virus (BKv) infections in rATG and basiliximab groups at year 1 and 3
6. Compare graft function, proteinuria in rATG and basiliximab groups at day 10, month 1, 3 and 6, year 1, 2 and 3
7. Compare incidence of primary and secondary outcomes (1 to 6) in subgroups defined by rank of transplantation
8. Health-Economics Analyses: to produce cost-utility and cost-effectiveness analyses (CUA and CEA) to determine the efficiency of rATG in comparison to basiliximab in sensitized KTRs without pre-existing DSAs, in terms of: a. Cost per Quality Adjusted Life Year (QALY) gained at 12 months b. Cost per prevented BPAR at 12 months

Conditions and MedDRA coding

Kidney transplant

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Patients aged between 18-79
2. At least one anti-HLA antibody identified by the Luminex Single Antigen test with MFI ≥ 2000
3. Graft incompatibility rate (TGI) < 85%
4. Ability for participant to understand the nature and objectives of the study; to comply with the requirements of the study
5. Written informed consent obtained from the participant
6. Participants covered by or entitled to social security

Exclusion criteria 16

1. DSA (positive virtual crossmatch with MFI threshold at 1000)
2. Combined transplantation
3. Beneficiaries of kidney transplants from donations after uncontrolled circulatory death (Maastricht II)
4. Incompatible ABO transplantation
5. Leukopenia lower than 3000/mm3
6. Thrombocytopenia (platelets < 50G/L)
7. Donor EBV Positive / Recipient EBV Negative
8. Active HIV infection (positive viral charge)
9. History of solid cancer (< 2 years), except to skin carcinoma (squamous-cell and basal-cell carcinoma)
10. History of lymphoma
11. Patients with severe uncontrolled systemic infection or severe allergy requiring acute or chronic treatment; Aspartate aminotransferase (ASAT), Alanine Amino Transferase (ALAT) or bilirubin greater than 3 times normal
12. Known hypersensitivity or contra-indication to Thymoglobulin® (rATG) or Simulect® (basiliximab) including the product excipients
13. Contra-indication to tacrolimus, mycophenolic acid and steroids
14. Pregnant or breastfeeding woman, or woman of childbearing potential not using an effective method of contraception, or having a desire to conceive, within 12 months of transplantation
15. Patient under judicial protection, deprivation of liberty
16. Participation in another interventional research with an investigational drug or medical device

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Incidence of BPAR (treated suspicious TCMR and confirmed TCMR with grade ≥ 1 and ABMR) in rATG and basiliximab groups during the first post-transplantation year, determined after blind central reading according to Banff 2019 classification

Secondary endpoints 8

1. Incidence of BPAR in rATG and basiliximab groups at year 3
2. Incidence of composite criteria including BPAR, death and graft loss (retransplantation or dialysis) at year 3.
3. Incidence of confirmed TCMR and ABMR in rATG and basiliximab groups at year 1 and 3.
4. Incidence of de novo DSA in rATG and basiliximab groups at year 1 and 3
5. Incidence of CMV viremia, CMV disease, BKv viremia and BKv nephropathy in rATG and basiliximab groups at year 1 and 3
6. Estimated glomerular filtration rate (eGFR) according to MDRD formula and proteinuria/creatinuria ratio in rATG and basiliximab groups at day 10, month 1, month 3 and 6, year 1, year 2 and 3
7. Incidence of primary and secondary outcomes (1 to 6) in subgroups defined by rank of transplantation
8. Health-Economics endpoints: a) Incremental Cost Utility Ratio (ICUR) estimating the “cost per QALY gained”, at 12 months, from the French Healthcare Insurance perspective, of rATG in comparison to basiliximab. b) Incremental Cost Effectiveness Ratio (ICER) estimating the “cost per prevented BPAR” at 12 months, from the French Healthcare Insurance perspective, of rATG in comparison to basiliximab.

Investigational products

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

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Regional Universitaire De Tours

Sponsor organisation

Centre Hospitalier Regional Universitaire De Tours

Address

2 Boulevard Tonnelle

City

Tours Cedex 9

Postcode

37044

Country

France

Scientific contact point

Organisation

Centre Hospitalier Regional Universitaire De Tours

Contact name

Coordinating Investigator

Public contact point

Organisation

Centre Hospitalier Regional Universitaire De Tours

Contact name

Coordinating Investigator

Locations

1 EU/EEA country · 16 investigational sites

By country

Investigational sites

Country notifications

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

Application history

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