Overview
Sponsor-declared trial summary
Phase
Therapeutic use (Phase IV)
Status
Expired
Participants planned
70
Countries
1
Sites
1
Prevention viral infection (BKV) poliamavirus after kidney trasplantation
to evaluate the role of adaptive immunity against to BKV and its modulation according to different immunosuppressive regimens used routinely in kidney transplantation, including mTor-i drugs.
Key facts
- Sponsor
- Fir Huvh Fundacio Institut De Recerca Hospital Universitari Vall De Hebron
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Virus Diseases [C02], Phenomena and Processes [G] - Immune system processes [G12]
- Decision date (initial)
- 2023-06-15
- Transition trial
- No
- Low-intervention
- Yes
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- Grant from ISCIII
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy, Prophylaxis
to evaluate the role of adaptive immunity against to BKV and its modulation according to different immunosuppressive regimens used routinely in kidney transplantation, including mTor-i drugs.
Secondary objectives 1
- T/B cell association specific against BKV and serological immunity through neutralizing antibodies (NAb) before and after transplantation and its relationship with the risk of developing BKV infection in a prospective cohort of renal transplant patients who receive standard IS or an mTor-i-based regimen.
Conditions and MedDRA coding
Prevention viral infection (BKV) poliamavirus after kidney trasplantation
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | PT | 10010185 | Complications of transplanted kidney | 100000004863 |
Study design 2 periods
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Kidney transplant patients with BK virus viral load in blood Transplant patients with BK virus infection in blood greater than 2 logarithms, whether previously enrolled in the trial or not, will be randomized to one of the two treatment groups.
Patients with a viral load less than 2 logs are expected to reduce their viral load spontaneously, without intervention. If at any time these patients exceed two logarithms they will be randomized to one of the two treatment groups.
|
Randomised Controlled | None | R1 Group: Patients who have a BK viral load of more than two logarithms in blood. Their dose of Myfortic or Cellcept will be reduced in half. If they do not reduce their viral load in the blood after 21 days, they will pass to group R2. R2 Group: Patients who have a BK viral load of more than two logarithms in blood. Treatment is changed from Cellcept or myfortic to Rapamune. |
|
| 2 | Patients who are going to receive a kidney transplant Patients who are going to receive a kidney transplant and who are going to be on a stable regimen and immunosuppression decided by their regular doctors.
|
Not Applicable | None | Cohort A: Patients who have an immunosuppression regimen based on sirolimus + tacrolimus + corticosteroids Cohort B: Patients who have an immunosuppression regimen based on MPA/MMF + tacrolimus + corticosteroids |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 8
- The patient must be at least 18 years old.
- The patient must be able to give informed consent in writing
- Patient receiving a kidney transplant.
- The patient must have a maintenance immunosuppressive regimen based on tacrolimus + MMF/MPS + corticosteroids or tacrolimus + rapamycin + corticosteroids.
- Patient with viral load detectable by PCR in peripheral blood against the BK-virus
- Kidney transplant patient at Vall d'Hebron Hospital at most 12 months before viral load detection.
- Stable renal function with an estimated glomerular filtration rate ≥ 35 ml/min/1.73 m2
- Urine protein/creatinine ratio value less than 1 g/g
Exclusion criteria 5
- Prior diagnosis of T cell-mediated or antibody-mediated rejection.
- Active cancer excluding non-melanocytic skin cancer
- Potentially Fertile Women who do not agree to use measures reliable contraceptives during the trial, who are pregnant, in period of breast-feeding or who present a positive pregnancy test at the time of their inclusion in the study
- Patients presenting with another severe systemic infection at the time of randomization.
- Patients with positive HIV serology
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- changes in immune response virus-specific at different biological levels, of patients who develop infection virus by the BK virus through the changes in BK virus viral load in peripheral blood of patients
Secondary endpoints 5
- Differences between groups of the specific effector polyfunctional T (IFN-y/IL2, IL-2, IFN-y, IL6, IL-4) response against different proteins VBK (LT-1, VP1) using FluorSPOT technique
- Differences Between Groups in Memory B Cell Response producer of specific IgG against BKV immunogenic proteins
- Differences between specific neutralizing antibodies (NAb), by using a system based on pseudovirions that express genotypes I-IV virus capsid proteins
- Differences in the specific immunophenotype by FACS multiparameter spectral analysis (AURORA, CyTEX Bioscience) of cells CD8+, CD4+ and NKT with special interest in exhaustion phenotypes that could be induced by using mTor-i (CD45RA and CD27; CD85j, CD161, CD16, CD56 CD161 and CD94 and KLRG1; or PD-1, TIM-3, LAG3, and DNAM-1).
- Differences in TCR signaling efficiency of cells Specific T against BKV
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
PRD3342088 · Product
- Active substance
- Sirolimus
- Substance synonyms
- SEL-110.36, RAPAMYCIN, NPG-12G, (3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,10,12,13,14,21,22,23,24,25,26,27,32,33,34,34a-Hexadecahydro-9,27-dihydroxy-3-[(1R)-2-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]-1-methylethyl]-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-23,27-epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclohentriacontine-1,5,11,28,29(4H,6H,31H)-pentone
- Pharmaceutical form
- COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 2 mg milligram(s)
- Max total dose
- 2 mg milligram(s)
- Max treatment duration
- 16 Week(s)
- Authorisation status
- Authorised
- ATC code
- L04AA10 — SIROLIMUS
- Marketing authorisation
- EU/1/01/171/007
- MA holder
- PFIZER EUROPE MA EEIG
- MA country
- Norway
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Comparator 4
PRD2153965 · Product
- Active substance
- Mycophenolate Mofetil
- Pharmaceutical form
- CAPSULE, HARD
- Route of administration
- ORAL
- Max daily dose
- 500 mg milligram(s)
- Max total dose
- 500 mg milligram(s)
- Max treatment duration
- 16 Week(s)
- Authorisation status
- Authorised
- ATC code
- L04AA06 — MYCOPHENOLIC ACID
- Marketing authorisation
- EU/1/96/005/001
- MA holder
- ROCHE REGISTRATION GMBH
- MA country
- Iceland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
CellCept 500 mg film-coated tablets
PRD2153968 · Product
- Active substance
- Mycophenolate Mofetil
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 1000 mg milligram(s)
- Max total dose
- 1000 mg milligram(s)
- Max treatment duration
- 16 Week(s)
- Authorisation status
- Authorised
- ATC code
- L04AA06 — MYCOPHENOLIC ACID
- Marketing authorisation
- EU/1/96/005/002
- MA holder
- ROCHE REGISTRATION GMBH
- MA country
- Iceland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Myfortic 180 mg comprimidos gastrorresistentes
PRD476850 · Product
- Active substance
- Mycophenolic Acid
- Substance synonyms
- MYCOPHENOLATE
- Pharmaceutical form
- GASTRO-RESISTANT TABLET
- Route of administration
- ORAL
- Max daily dose
- 360 mg milligram(s)
- Max total dose
- 360 mg milligram(s)
- Max treatment duration
- 16 Week(s)
- Authorisation status
- Authorised
- ATC code
- L04AA06 — MYCOPHENOLIC ACID
- Marketing authorisation
- 66.140
- MA holder
- NOVARTIS FARMACÉUTICA S.A.
- MA country
- Spain
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Myfortic 360 mg Comprimidos gastrorresistentes
PRD475366 · Product
- Active substance
- Mycophenolic Acid
- Substance synonyms
- MYCOPHENOLATE
- Pharmaceutical form
- GASTRO-RESISTANT TABLET
- Route of administration
- ORAL
- Max daily dose
- 720 mg milligram(s)
- Max total dose
- 720 mg milligram(s)
- Max treatment duration
- 16 Week(s)
- Authorisation status
- Authorised
- ATC code
- L04AA06 — MYCOPHENOLIC ACID
- Marketing authorisation
- 5052188
- MA holder
- NOVARTIS FARMA - PRODUTOS FARMACÊUTICOS S.A.
- MA country
- Portugal
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Fir Huvh Fundacio Institut De Recerca Hospital Universitari Vall De Hebron
- Sponsor organisation
- Fir Huvh Fundacio Institut De Recerca Hospital Universitari Vall De Hebron
- Address
- Passeig De La Vall D'hebron 119-129
- City
- Barcelona
- Postcode
- 08035
- Country
- Spain
Scientific contact point
- Organisation
- Fir Huvh Fundacio Institut De Recerca Hospital Universitari Vall De Hebron
- Contact name
- Oriol Bestard Matamoros
Public contact point
- Organisation
- Fir Huvh Fundacio Institut De Recerca Hospital Universitari Vall De Hebron
- Contact name
- Oriol Bestard Matamoros
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Spain | Expired | 70 | 1 |
| Rest of world | — | 0 | — |
Investigational sites
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-03-15 | Spain | Acceptable 2023-06-15
|
2023-06-15 |