PREPARE-iVAC

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitair Medisch Centrum Groningen, Universitair Medisch Centrum Groningen

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20], Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutics [E02], Diseases [C] - Virus Diseases [C02]

Trial duration

22 Aug 2023 → 27 Feb 2024

Decision date (initial)

2023-06-01

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

The Netherlands Organisation for Health Research and Development (ZonMw) · Dutch Kidney Foundation (Nierstichting)

External identifiers

EU CT number

2023-503894-39-00

WHO UTN

U1111-1290-1724

ClinicalTrials.gov

NCT05924685

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Prophylaxis, Efficacy

To investigate whether replacement of MMF/MPA by everolimus in kidney transplant recipients results in superior immunogenicity of COVID-19 vaccination as measured by neutralizing antibody titers

Secondary objectives 7

1. To investigate whether replacement of MMF/MPA by everolimus in kidney transplant recipients results in superior humoral immunogenicity of COVID-19 vaccination as measured by SARS-CoV-2 specific antibody levels
2. To investigate whether replacement of MMF/MPA by everolimus in kidney transplant recipients results in superior humoral immunogenicity of herpes zoster vaccination as measured by varicella zoster specific antibody levels
3. To investigate whether replacement of MMF/MPA by everolimus in kidney transplant recipients results in superior cellular immunogenicity of COVID-19 vaccination
4. To investigate whether replacement of MMF/MPA by everolimus in kidney transplant recipients results in superior cellular immunogenicity of herpes zoster vaccination
5. To evaluate safety of replacement of MMF/MPA by everolimus in terms of incidence of acute rejection, kidney function decline, incidence of (serious) adverse events (S)AEs))
6. To evaluate safety of replacement of MMF/MPA by everolimus on the incidence of adverse events of COVID-19 vaccination
7. To evaluate safety of replacement of MMF/MPA by everolimus on the incidence of adverse events of herpes zoster vaccination

Conditions and MedDRA coding

kidney transplantation

Study design 1 period

Regulatory references

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Age ≥ 18 years
2. ≥6 months after kidney transplantation
3. Eligible for the vaccinations as described by the instructions of the manufacturers of the vaccines (e.g. received 3 previous COVID-19 vaccinations as part of the primary COVID-19 immunisation)
4. Capable of understanding the purpose and risks of the study, fully informed and given written informed consent (signed informed consent form has been obtained)
5. Willing to adhere to the protocol and be available during the study period
6. Maintenance immunosuppressive therapy consisting of either triple or dual therapy including MMF/MPA with a minimum daily dose of 1000 mg (MMF) or 720 mg (MPA) and a CNI

Exclusion criteria 23

1. Multi-organ transplant recipient
2. Subjects with severe systemic infections, current or within the two weeks prior to randomisation
3. Subjects with severe restrictive or obstructive pulmonary disorders
4. Subjects with severe hypercholesterolemia or hypertriglyceridemia that cannot be controlled
5. Subjects with white blood cell (WBC) count ≤ 2,000/mm3 or with platelet count ≤ 50,000/mm3 at last outpatient clinic visit
6. Proteinuria > 1 gram/day at last outpatient clinic visit
7. Contra-indications for use of everolimus according to the opinion of the treating physician
8. Additional for part 2: Herpes zoster vaccination with the live attenuated vaccine (Zostavax) or varicella vaccination (Provarivax) during the conduct of the study
9. Additional for part 2: Previous herpes zoster vaccination with the RZV
10. Simultaneous participation in another interventional study that will likely influence the study outcomes
11. History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (e.g. anaphylaxis) to any component of the study intervention(s)
12. Active COVID-19 disease
13. Additional for part 2: Active varicella or herpes zoster disease
14. Active malignancy, except non-melanoma skin cancer
15. Inherited immune deficiency
16. Infection with Human Immunodeficiency Virus (HIV)
17. Administration of T-cell, B-cell, or plasma cell depleting antibodies during the last 6 months
18. Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection
19. Previous CNI trough levels not sufficient according to the discretion of the treating physician
20. More than two previous kidney transplantations
21. Calculated level of panel reactive antibodies prior to last transplantation above 85%
22. Evidence of DSAs
23. Signs of acute rejection during the preceding year

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The neutralizing antibody titer against the Omicron XBB.1.5 strain 28 days after monovalent Omicron XBB.1.5. COVID-19 vaccination in patients continuing MMF/MPA compared to patients who switched to everolimus.

Secondary endpoints 11

1. SARS-CoV-2 specific anti-S1 antibody level at 28 days after COVID-19 vaccination
2. Varicella zoster specific anti-gE antibody level 28 days after 1st and 2nd herpes zoster vaccination
3. SARS-CoV-2 specific T-cell response at 28 days after COVID-19 vaccination
4. Varicella zoster specific T-cell response at 28 days after 2nd herpes zoster vaccination
5. Incidence of treated acute rejection
6. Change in estimated glomerular filtration rate and proteinuria during the study
7. Incidence of serious adverse events throughout the study
8. Incidence of adverse events of special interest throughout the study
9. Incidence of dnDSAs at V7, or when not participating in second part of the study at V5.
10. Incidence of solicited adverse events of COVID-19 vaccination during 7 days after vaccination
11. Incidence of solicited adverse events of herpes zoster vaccination during 7 days after each vaccination

Investigational products

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

Test 4

Comparator 5

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitair Medisch Centrum Groningen

Sponsor organisation

Universitair Medisch Centrum Groningen

Address

Hanzeplein 1

City

Groningen

Postcode

9713 GZ

Country

Netherlands

Scientific contact point

Organisation

Universtity Medical Center

Contact name

Project leader

Public contact point

Organisation

Universtity Medical Center

Contact name

Project leader

Universitair Medisch Centrum Groningen

Sponsor organisation

Universitair Medisch Centrum Groningen

Address

Hanzeplein 1

City

Groningen

Postcode

9713 GZ

Country

Netherlands

Scientific contact point

Organisation

Universitair Medisch Centrum Groningen

Contact name

Project Leader

Public contact point

Organisation

Universitair Medisch Centrum Groningen

Contact name

Project Leader

Locations

1 EU/EEA country · 7 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 2 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

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