A Phase-I Study of a Nanoparticle-based Peptide Vaccine Against Dengue Virus

NCT ID: NCT04935801

Last Updated: 2022-12-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-02
• Study Completion Date: 2022-09-15

Brief Summary

This trial aims to test the safety of 2 doses of a T-cell priming specific cocktail of Dengue viruses peptides representing all 4 DENV serotypes and mounted on a gold nanoparticle.

NOTE: This is the master protocol of a prospective 2-stage adaptive trial, which aims to add and test a Coronavirus vaccine candidate as well, in an identical trial design.

Detailed Description

A critical limitation for Dengue vaccines is their association with antibody-dependent enhancement, where poorly formed immune responses predispose the individual to severe disease during a second infection. Thus, a more targeted vaccine (inducing / priming T cells and not producing antibodies) could be the best alternative and most successful preventive method in the fight against severe manifestations of the disease.

Nanoparticle antigen delivery systems have been developed to enrich specific targeting of immune receptors. These carrier systems are designed to facilitate antigen uptake and processing by antigen presenting cells (APCs), as well as to control antigen release and protect them from premature proteolytic degradation. This more targeted response also allows us to reduce the effective antigen dose (to nanomoles) and mimic a replicating infection with zero risk of developing the infectious disease.

The hypotheses are listed below:

1. During the COVID-19 pandemic, Dengue virus disease is likely to cause significant diagnostic confusion and it risks further progression due to disrupted control measures.

2. As the SARS-CoV-2 pandemic devastates the world, the need for highly efficient and scalable vaccines is desperately required.

3. Peptide vaccines have high potential as a rapidly scalable modular platform for emerging diseases requiring targeted immunological responses.

4. Dengue viruses and Coronaviruses (e.g. COVID-19 causing viruses) are particularly well suited to this approach.

For this initial naNO-DENGUE part of the trial, the objectives are as follows:

Primary:

To evaluate the safety and reactogenicity of two intradermal injections of two different doses of the investigational Dengue peptide T cell inducing vaccine (PepGNP-Dengue) administered to healthy volunteers as a:

1. candidate vaccine for the prevention of Dengue

2. proof-of-concept for a rapidly scalable modular peptide vaccine platform, which will be followed by a COVID-19 construct after interim analyses.

Secondary:

1. To assess the evidence of a T-cell mediated immune response as a surrogate of protection against severe dengue disease using a novel peptide set-point vaccine in healthy adults.

2. To check the absence of an antibody mediated response

For naNO-DENGUE, a total of 26 eligible participants will be randomized into the following groups:

• Group 1 (n=13): 10 Low Dose (LD) PepGNP-Dengue (2.5 nmol) + 3 Comparator
• Group 2 (n=13): 10 High Dose (HD) PepGNP-Dengue (7.5 nmol) + 3 Comparator, Thus, 20/26 vaccine vera and 6/26 Comparator controls. Allocations of vaccine vera vs Comparator for each group are double-blinded. Each arm will be staggered into a "Pioneer" group (3/13 participants) followed a week later after a safety review by the remaining 10/13 "Followers".

This is the master protocol for a 2-stage study investigating the safety of 2 vaccines from a T Cell priming vaccine platform for emerging diseases:

Stage 1: naNO-DENGUE A Phase-I study of a nanoparticle-based peptide vaccine against Dengue (Master protocol) Stage 2: naNO-COVID A Phase-I study of a nanoparticle-based peptide vaccine against SARS-CoV2 (Sub-protocol)

Conditions

Dengue

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

LD Vehicle_GNP

Low dose (LD) comparator (2.5nmol) - gold nanoparticle (14.8ug) without peptides

Group Type: SHAM_COMPARATOR

LD vehicle-GNP

Intervention Type: BIOLOGICAL

Two intradermal injections in the upper arm spaced 21 days apart

LD PepGNP-Dengue

Low dose (LD) peptide vaccine (2.5nmol) - gold nanoparticle (14.8ug) plus peptides

Group Type: EXPERIMENTAL

LD PepGNP-Dengue

Intervention Type: BIOLOGICAL

Two intradermal injections in the upper arm spaced 21 days apart

HD vehicle-GNP

High dose (HD) comparator (7.5nmol) - gold nanoparticle (44.5ug) without peptides

Group Type: SHAM_COMPARATOR

HD vehicle-GNP

Intervention Type: BIOLOGICAL

Two intradermal injections in the upper arm spaced 21 days apart

HD PepGNP-Dengue

High dose (HD) peptide vaccine (7.5nmol) - gold nanoparticle (44.5ug) plus peptides

Group Type: EXPERIMENTAL

HD PepGNP-Dengue

Intervention Type: BIOLOGICAL

Two intradermal injections in the upper arm spaced 21 days apart

Interventions

LD vehicle-GNP

Two intradermal injections in the upper arm spaced 21 days apart

Intervention Type: BIOLOGICAL

LD PepGNP-Dengue

Two intradermal injections in the upper arm spaced 21 days apart

Intervention Type: BIOLOGICAL

HD vehicle-GNP

Two intradermal injections in the upper arm spaced 21 days apart

Intervention Type: BIOLOGICAL

HD PepGNP-Dengue

Two intradermal injections in the upper arm spaced 21 days apart

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Aged 18 to 45 years on the day of inclusion
• Participant signed informed consent
• Residing in Switzerland

Exclusion Criteria

• Participant is pregnant, lactating, or of childbearing potential
• Participation in the 4 weeks preceding the first trial vaccination or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure
• Receipt of any vaccine in the 4 weeks preceding the first trial vaccination (excepting influenza vaccination, which may be received up to 2 weeks before first study vaccine) or planned receipt of any vaccine in the 4 weeks following each trial vaccination.
• Previous vaccination against Japanese encephalitis (JE), Yellow Fever (YF), or any dengue virus vaccine (monovalent or tetravalent) at any time in the past with either a trial vaccine or another vaccine (commercial or investigational) based on medical history
• Self-reported or documented history of flavivirus (FV) infection (e.g. DENV, YF, WNV, JE, TBE), confirmed either clinically or serologically
• Receipt of immunoglobulins, blood or blood-derived products in the past 3 months
• Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy
• Self-reported or documented seropositivity for human immunodeficiency virus (HIV), hepatitis B natural infection (HBcAb positive serology), or hepatitis C
• Previous residence for more than 12 months in, or travel in the last 30 days to FV-endemic regions (excluding TBE and WNV)
• At high risk for dengue infection during the trial
• Known systemic hypersensitivity to any of the vaccine components (e.g. gold), or history of a life-threatening reaction to vaccines, or to a vaccine containing any of the same substances
• Current alcohol abuse or drug addiction (reported or suspected)
• Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion
• Thrombocytopenia or any coagulation disorder
• Identified as an Investigator or employee of the Investigator or study centre with direct involvement in the proposed study, or identified as an immediate family member (i.e., parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study (i.e. in the employment of the Tropivac clinic or DFRI unit at Unisanté).
• Refusal to be informed in the event that relevant results concerning the participant's health are revealed.

The following events constitute contraindications to the administration of the investigational product on the day of planned vaccination.

The participant must be followed until resolution of the event as with any medical event and may be considered for vaccination at a later date (maximum 14 days later) or withdrawn at the discretion of the Investigator. Delays due to these events do not constitute a protocol deviation.

• Temperature of >37.5°C at the time of vaccination
• Acute disease at the time of vaccination
• If there is a clinical/epidemiological suspicion of COVID-19 (according to the clinician's judgement), the participant will be asked to first take a PCR/rapid test for SARS-CoV2, and the vaccination will be delayed until the result comes back negative and the symptoms have resolved.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Center for Primary Care and Public Health (Unisante), University of Lausanne, Switzerland

OTHER

Sponsor Role: collaborator

University of Lausanne Hospitals

OTHER

Sponsor Role: collaborator

Gylden Pharma Ltd

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Blaise Genton, Prof

Role: PRINCIPAL_INVESTIGATOR

Center for Primary Care and Public Health (Unisante), University of Lausanne, Switzerland

Locations

Center for Primary Care and Public Health, (Unisante)

Lausanne, Canton of Vaud, Switzerland

Countries

Switzerland

Other Identifiers

naNO-DENGUE

Identifier Type: -

Identifier Source: org_study_id