YF_PROTECT: Prophylactic treatment with sofosbuvir for Yellow Fever

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Leids Universitair Medisch Centrum (LUMC)

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

11 Sep 2024 → 2 Apr 2025

Decision date (initial)

2024-08-22

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

ZonMw grant, program: Infectieziektebestrijding · Leiden University Medical Center (LUMC)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis

To assess the effect of sofosbuvir on YF17D replication.

Secondary objectives 3

1. To monitor adverse events due to sofosbuvir use in combination with yellow fever vaccination.
2. To monitor biochemical abnormalities due sofosbuvir use in combination with yellow fever vaccination
3. Exploratory objective: To assess if theoretically potent levels of sofosbuvir are achieved.

Conditions and MedDRA coding

Healthy volunteers

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Male and female sex
2. Participants between 18 and 50 years
3. Participants that are generally healthy without substantial comorbidities, especially no primary or secondary immunodeficiencies. Patients with chronic diseases other than those mentioned in the exclusion criteria below and which are stable, defined as not requiring change of therapy or hospitalization in the six weeks preceding study enrolment, may be eligible for this study. This will be decided by the researcher who is medically responsible.

Exclusion criteria 18

1. Previous yellow fever vaccination
2. Vaccination with other vaccines < 1 month before inclusion
3. Use of anticoagulants
4. Current use (or in previous 2 weeks) of p-glycoprotein / BCRP inducers such as rifampicin, seizure medication or St. John Wort plant extracts
5. Use of antihyperglycemic drugs or documented diabetes mellitus
6. Current use (or in previous 3 months) of amiodaron
7. History of liver disease
8. Documented end-stage kidney disease or eGFR <30ml/min
9. Previous yellow fever infection
10. Documented primary or secondary immunodeficiencies
11. Thymic disfunction (such as thymoma, thymectomy, thymic radiation treatment, myasthenia gravis or DiGeorge syndrome)
12. Multiple sclerosis
13. Pregnancy at time of inclusion (pregnancy test is performed at inclusion)
14. Breastfeeding during the course of the study
15. Known chicken-egg allergy
16. Known hypersensitivity to any other of the vaccine components
17. Participation in another clinical trial in which life-attenuated viruses are contraindicated and which might jeopardize participants safety
18. Planned travel to a yellow fever endemic country within four months after start of the study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. viremia (YF17D virus in plasma) at any time (yes/no)
2. and/ or viruria (YF17D in urine) at any time (yes/no)
3. and/ or neutralizing antibodies on D28 after vaccination (yes/no)

Secondary endpoints 4

1. Adverse events of sofosbuvir (diary with an SmPC based symptom questionnaire and reporting of any unsolicited adverse events)
2. Increase in ALT and bilirubin, and decrease in Hb levels on day 5* and 28 after vaccination compared to day 0 in the sofosbuvir treatment group. * For group B this will be done on day 2, do make sure the sample is taken within reasonable time after sofosbuvir use
3. Differences in ALT, bilirubin and blood count (i.e., haemoglobin, thrombocytes, leukocyte differentiation) between the sofosbuvir treatment and no treatment group
4. Exploratory endpoint: Plasma is stored for determination of sofosbuvir concentration, which will only be measured when viremia or viruria or yellow fever neutralizing antibodies are not absent/decreased in participants in the sofosbuvir treatment group

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Leids Universitair Medisch Centrum (LUMC)

Sponsor organisation

Leids Universitair Medisch Centrum (LUMC)

Address

Albinusdreef 2

City

Leiden

Postcode

2333 ZA

Country

Netherlands

Scientific contact point

Organisation

Leids Universitair Medisch Centrum (LUMC)

Contact name

dr. A.H.E. (Anna) Roukens

Public contact point

Organisation

Leids Universitair Medisch Centrum (LUMC)

Contact name

dr. A.H.E. (Anna) Roukens

Locations

1 EU/EEA country · 1 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 15 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