Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Authorised, recruiting
Participants planned
25
Countries
1
Sites
5
Early graft dysfunction after heart transplant
The main objective is to observe a significant improvement in DFG (clearance calculated according to the CKD EPI formula) of 20 ml/min between M3 and M12 post TC, in cardiac transplant patients at risk of CKD, treated with 9 monthly infusions of belatacept associated with a progressive decrease in calcineurin inhibitor…
Key facts
- Sponsor
- Centre Hospitalier Universitaire De Nantes
- 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
- 4 Sep 2024 → ongoing
- Decision date (initial)
- 2024-09-04
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
External identifiers
- EU CT number
- 2024-516541-40-00
- EudraCT number
- 2019-001510-42
- ClinicalTrials.gov
- NCT04180085
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Efficacy
The main objective is to observe a significant improvement in DFG (clearance calculated according to the CKD EPI formula) of 20 ml/min between M3 and M12 post TC, in cardiac transplant patients at risk of CKD, treated with 9 monthly infusions of belatacept associated with a progressive decrease in calcineurin inhibitors.
Secondary objectives 4
- Demonstrate that if there is a risk of rejection (> grade 2) it is less than 30% during the first year of the heart transplant as found in the literature (non-inferiority criterion)
- Quantify the percentage of patients developing NODAT (New Onset Diabetes After Transplantation) at M3 and M12 post-TC (Estimate)
- Evaluate the mortality specific to M12 post TC (Estimate).
- Evaluate the use of renal replacement therapy between M3 and M12 post-TC.
Conditions and MedDRA coding
Early graft dysfunction after heart transplant
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.1 | LLT | 10064694 | Heart graft dysfunction | 10022117 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 9
- Cardiac transplant patients for 3 months
- Over 18 years of age
- No DSA at D0 (positive threshold MFI> 2000)
- Having a DFG < 30ml/min calculated according to the formula CKD EPI or a decrease in DFG of more than 50% between the day of the heart transplant and M3, stable for 15 days.
- EBV positive serology
- Having signed the consent after receiving informed information
- Negative pregnancy test for patients of childbearing age, and agreement to use effective contraception throughout the study and 6 weeks after the end of the study
- Having no difficulty in understanding and communicating with the investigator and his representatives
- Beneficiaries of a Social Security scheme
Exclusion criteria 8
- 2nd heart transplant or other solid organ transplant
- History of rejections
- Cellular or humoral rejection at myocardial biopsy of M3 post TC Current viral infection of type CMV, EBV, HCV, HBV.....
- HIV positive serology
- Ongoing participation in another clinical study
- Any clinical condition that the investigator considers incompatible with the conduct of the study under acceptable safety conditions Inability of the patient to comply with study procedures
- Pregnant or breastfeeding women
- Person under guardianship, curatorship or safeguard of justice
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Determination of plasma creatinine and calculation of clearance according to the formula CKD EPI at M3 and M12 post HT.
Secondary endpoints 5
- - Myocardial biopsies between M3 and M12 post HT
- - Anti-HLA antibody testing according to the habits of heart transplant centres
- - Fasting blood glucose and HBA1C at M3 and M12 post HT
- - Death
- - Number of dialysis sessions between M3 and M12 post HT
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
NULOJIX 250 mg powder for concentrate for solution for infusion
PRD2333424 · Product
- Active substance
- Belatacept
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 6 mg/kg milligram(s)/kilogram
- Max total dose
- 54 mg/kg milligram(s)/kilogram
- Max treatment duration
- 9 Day(s)
- Authorisation status
- Authorised
- ATC code
- L04AA28 — -
- Marketing authorisation
- EU/1/11/694/001
- MA holder
- BRISTOL-MYERS SQUIBB PHARMA EEIG
- MA country
- Iceland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Auxiliary 3
PRD10226907 · Product
- Active substance
- Tacrolimus
- Pharmaceutical form
- CAPSULE, HARD
- Route of administration
- ORAL USE
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 1755 mg milligram(s)
- Max treatment duration
- 11 Month(s)
- Authorisation status
- Authorised
- ATC code
- L04AD02 — -
- Marketing authorisation
- 8913/2016/02
- MA holder
- ASTELLAS PHARMA EUROPE B.V.
- MA country
- Romania
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD11347538 · Product
- Active substance
- Ciclosporin
- Substance synonyms
- CYCLOSPORINE, CICLOSPORINE, CYCLOSPORIN
- Pharmaceutical form
- CAPSULE, SOFT
- Route of administration
- ORAL USE
- Max daily dose
- 200 mg milligram(s)
- Max total dose
- 36000 mg milligram(s)
- Max treatment duration
- 11 Month(s)
- Authorisation status
- Authorised
- ATC code
- L04AD01 — -
- Marketing authorisation
- PA 0896/024/003
- MA holder
- NOVARTIS IRELAND LIMITED
- MA country
- Ireland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Advagraf 5 mg prolonged-release hard capsules
PRD324633 · Product
- Active substance
- Tacrolimus
- Pharmaceutical form
- PROLONGED-RELEASE CAPSULE, HARD
- Route of administration
- ORAL USE
- Max daily dose
- 5 mg milligram(s)
- Max total dose
- 877.5 mg milligram(s)
- Max treatment duration
- 11 Month(s)
- Authorisation status
- Authorised
- ATC code
- L04AD02 — -
- Marketing authorisation
- EU/1/07/387/007
- MA holder
- ASTELLAS PHARMA EUROPE B.V.
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Centre Hospitalier Universitaire De Nantes
- Sponsor organisation
- Centre Hospitalier Universitaire De Nantes
- Address
- 5 Allee De L Ile Gloriette, Cs 69301 Cs 69301
- City
- Nantes Cedex 1
- Postcode
- 44093
- Country
- France
Scientific contact point
- Organisation
- Centre Hospitalier Universitaire De Nantes
- Contact name
- Claire Garandeau
Public contact point
- Organisation
- Centre Hospitalier Universitaire De Nantes
- Contact name
- Claire Garandeau
Locations
1 EU/EEA country · 5 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| France | Authorised, recruiting | 25 | 5 |
| Rest of world | — | 0 | — |
Investigational sites
Centre Hospitalier Universitaire De Nantes
Nephrology, 38 Boulevard Jean Monnet, 44000, Nantes
Centre Hospitalier Universitaire De Bordeaux
Cardiology, Avenue De Magellan, 33600, Pessac
Hospices Civils De Lyon
Cardiology, 28 Avenue Du Doyen Jean Lepine, 69500, Bron
Centre Hospitalier Universitaire De Rennes
Nephrology, 2 Rue Henri Le Guilloux, 35000, Rennes
Centre Hospitalier Universitaire De Nantes
Cardiology, Boulevard Du Professeur Jacques Monod, 44800, Saint Herblain
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| France | 2024-09-04 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 9 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocole 2024-516541-40-00 | 5 |
| Protocol (for publication) | D1_SoC_Protocol_2024-516541-40-00 | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements_2024-516541-40-00 | 1 |
| Subject information and informed consent form (for publication) | L1_ICF | 3 |
| Subject information and informed consent form (for publication) | L1_SIS | 3 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC NULOJIX | 1 |
| Synopsis of the protocol (for publication) | D1_SoC_Protocol synopsis_2024-516541-40-00 | 1 |
| Synopsis of the protocol (for publication) | D1-Protocole Synopsis_2024-516541-40-00 | 5 |
| Synopsis of the protocol (for publication) | D1-Protocole Synopsis_2024-516541-40-00_TC | 5 |
Application history
3 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-07-18 | France | Acceptable 2024-08-09
|
2024-09-04 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-11-05 | France | Acceptable 2024-11-25
|
2024-12-12 |
| 3 | SUBSTANTIAL MODIFICATION | SM-3 | 2025-11-21 | France | Acceptable 2026-01-07
|
2026-01-07 |