A randomized first-in-human, Phase 1, single-center, observer-blind, active-controlled 3-arm study to evaluate the safety, tolerability, and immunogenicity of one single administration of TETRALITE, a novel adjuvanted influenza vaccine, in healthy participants aged 18 to 50 years

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Litevax B.V.

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

14 Sep 2022 → 17 May 2023

Decision date (initial)

2022-08-03

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Safety

The primary objective is to evaluate safety and tolerability of a single administration of TETRALITE (3 ug VaxigripTetra + 1 mg or 4 mg adjuvant) versus 15 ug VaxigripTetra without adjuvant in healthy participants (18-50 years).

Secondary objectives 1

1. To evaluate the humoral immune responses of a single administration of TETRALITE (3 ug VaxigripTetra + 1 mg or 4 mg adjuvant) versus 15 ug VaxigripTetra without adjuvant in healthy participants (18 – 50 years).

Conditions and MedDRA coding

Influenza

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Written signed informed consent obtained before any study-related activities.
2. Aged 18 to 50 years inclusive, at the time of signing the ICF.
3. Participants who are considered to be in good general health as determined by medical evaluation including medical history, physical examination and laboratory tests within 21 days prior to enrollment.
4. Participants with a BMI within the range 18.5 to 35 kg/m2 inclusive at screening.
5. Women who are not pregnant or breastfeeding, and one of the following conditions applies: 1/ Women of non-childbearing potential (WONCBP) as defined in Appendix 1: Contraceptive and Barrier Guidance. Non-childbearing potential is defined as surgically sterilized (e.g. hysterectomy, bilateral oophorectomy, or tubal ligation/salpingectomy) or postmenopausal (defined as having no menstrual bleeding for at least 12 months) without an alternative medical cause prior to study. OR 2/ WOCBP and using an acceptable contraceptive method as defined and described in Appendix 1 from at least 1 month prior to study vaccination and for 3 months post-vaccination. The investigator should evaluate the potential for contraceptive method failure (e.g. noncompliance, recently initiated) in relationship to study vaccination. During the study period, all female participants should practice at least one highly effective contraception for 3 months post-vaccination. Effective contraception is defined as stabilized on oral birth control for at least 1 month before study participation, intrauterine device/system, implant, injection, transdermal patch, vasectomized partner or abstinence.
6. WOCBP must have a negative serum pregnancy test at screening and a negative urine pregnancy test before vaccination at Day 1. Refer to Section 8.3.5, Pregnancy Testing. The investigator is responsible for review of medical history and menstrual history to decrease the risk for inclusion of a woman with an early undetected pregnancy.
7. Participants who are willing and able to comply with the study procedures and are in the view of the investigator capable of completing the study.

Exclusion criteria 30

1. History of previous laboratory confirmed influenza infection in the past 12 months, excluding laboratory confirmed COVID-19 infections, prior to the day of study vaccination.
2. Positive (in the past, suspected or ongoing) for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, and human immunodeficiency virus (HIV) antibody.
3. Past or current history of immune mediated and/or autoimmune diseases as indicated by the investigator, e.g. diabetes mellitus (type I or II, with the exception of gestational diabetes) and thyroid disease.
4. Serious reactions to vaccines that preclude receipt of study vaccinations as determined by the investigator.
5. Clinical conditions representing a contraindication for IM administration, as judged by the investigator, e.g. history of bleeding disorder (e.g. factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with IM administration or blood draws.
6. History of confirmed hypersensitivity, allergy and/or anaphylaxis to eggs (ovalbumin or chicken proteins), squalene-based adjuvants, or other components of the study vaccine (neomycin, formaldehyde or octoxinol-9).
7. Current history of uncontrolled medical illness (unstable for the past 3 months) as indicated by investigator, e.g. hypertension.
8. Past or current history of any neurological disorder, e.g. Guillain-Barré syndrome and seizure disorder other than: 1) febrile seizures, 2) seizures secondary to alcohol withdrawal more than 3 years ago, or 3) seizures that have not required treatment within the last 3 years.
9. History of asplenia, functional asplenia or any condition resulting in the absence or removal of the spleen.
10. Active malignancy or malignancy within the past 5 years.
11. Asthma that is unstable or required emergent care, urgent care, hospitalization or intubation during the past two years or that is expected to require the use of oral or intravenous corticosteroids.
12. History of hereditary angioedema (HAE), acquired angioedema (AAE) or idiopathic forms of angioedema.
13. History of idiopathic urticaria within the past year.
14. History of heavy smoking, drug - or alcohol abuse/addiction (including alcohol dependence), or psychiatric condition (e.g. past or present psychoses; disorder requiring lithium; or within 5 years prior to administration of study vaccine, a history of suicide plan or attempt), which in investigator’s opinion could compromise the participant’s safety and/or compliance with the protocol.
15. A rash, dermatological condition or tattoos that would, in the opinion of the investigator, interfere with injection local reaction rating.
16. Prior seasonal or pandemic influenza vaccination in the 6 months before administration of study vaccine or planning to receive the influenza vaccination during the study period.
17. Prior receipt of investigational pandemic influenza vaccination in the 3 months before administration of study vaccine or planning to receive such product during the study period.
18. Prior receipt of a live attenuated vaccination in the 28 days prior to administration of study vaccine, or within 14 days for subunit or inactivated vaccines other than seasonal or pandemic influenza vaccination, excluding COVID-19 vaccine.
19. Prior receipt of COVID-19 vaccine in the 7 days before administration of study vaccine, or planning to receive a COVID-19 vaccine during the first 14 days following study vaccination.
20. Planning to receive a vaccine during the first 28 days following the administration of study vaccine, other than COVID-19 vaccine.
21. Currently participating in another clinical study, or planning to participate in another study during the study period, or administration of any investigational drug or medical device in the 4 weeks prior to study vaccination.
22. Prior receipt of blood, blood-derived products or immunoglobulins in the 6 months prior to administration of study vaccine, or planning to receipt such product during the study period.
23. Use of drugs that can affect immune response such as systemic corticosteroids (excluding topical preparations and inhaled preparations) or immunosuppressive drugs in the 30 days before study vaccination and/or in the first 28 days following study vaccination, with the exceptions that a short course of corticosteroids ≤10 days duration, or a single injection for a self-limited condition at least 2 weeks prior to enrollment will not exclude study participation.
24. Current intake of drugs that increase bleeding risk, e.g. anticoagulant medication (coumarin derivatives, low molecular weight heparin, direct-acting oral anticoagulant medication [DOAC]).
25. Current anti-tuberculosis prophylaxis or therapy.
26. Use of non-steroidal anti-inflammatory drugs (NSAIDs) and/or planning a medical procedure under full anesthesia on the day of study vaccination and/or in the first 14 days following study vaccination with the exception of a medical indication.
27. WOCBP who are pregnant, breast-feeding or planning to become pregnant during the study.
28. Participants with history of any medical conditions that, in opinion of the investigator, might interfere with the results of the study or pose additional risk to the participants due to participation in the study.
29. Current febrile illness (oral temperature >38.0 °C) or other acute illness prior to vaccine administration. Participants with oral temperature >38.0 °C can be rescheduled to when they are at least 72 hours feverless.
30. Intake of antipyretics and/or analgesic medications within 24 hours prior to study vaccination. Reason for use (prophylaxis or treatment) should be documented. Participants can be rescheduled after being 24 hours free of intake of antipyretics and/or analgesic medications.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Occurrence of solicited local and systemic AEs for 7 days after vaccination.
2. Occurrence of unsolicited AEs for 28 days after vaccination.
3. Occurrence of serious adverse events (SAEs), potential immune mediated disorders (pIMDs) and adverse events of special interest (AESIs) for 180 days after vaccination.
4. Occurrence of clinically abnormal hematology and serum biochemistry laboratory values at 7 days, 28 days and 180 days after vaccination versus baseline (Day 1, pre-vaccination).

Secondary endpoints 2

1. Immunogenicity of TETRALITE with different adjuvant dose levels as determined by: The HI antibody titers in serum samples against the 4 vaccine influenza strains at 7 days, 28 days and 180 days after vaccination versus baseline (Day 1, pre-vaccination).
2. Immunogenicity of TETRALITE with different adjuvant dose levels as determined by: The MN antibody titers in serum samples against the 4 vaccine influenza strains at 7 days, 28 days and 180 days after vaccination versus baseline (Day 1, pre-vaccination).

Investigational products

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

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Litevax B.V.

Sponsor organisation

Litevax B.V.

Address

Akkersestraat 50

City

Ophemert

Postcode

4061 BJ

Country

Netherlands

Scientific contact point

Organisation

Litevax B.V.

Contact name

Luuk Hilgers

Public contact point

Organisation

Litevax B.V.

Contact name

Luuk Hilgers

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 5 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