NCT04935801

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

naNO-DENGUE: A Phase I Double-blind, Randomized, Vehicle-controlled, Dose-finding, Safety Study of a Synthetic Nanoparticle-based, T-Cell Priming Peptide Vaccine Against Dengue Virus in Healthy Adults in Switzerland

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 26 (actual)
• Sponsor: Gylden Pharma Ltd · Industry
• Sex: All
• Age: 18 Years – 45 Years
• Healthy volunteers: Accepted

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

Interventions

Type	Name	Description
BIOLOGICAL	LD vehicle-GNP	Two intradermal injections in the upper arm spaced 21 days apart
BIOLOGICAL	LD PepGNP-Dengue	Two intradermal injections in the upper arm spaced 21 days apart
BIOLOGICAL	HD vehicle-GNP	Two intradermal injections in the upper arm spaced 21 days apart
BIOLOGICAL	HD PepGNP-Dengue	Two intradermal injections in the upper arm spaced 21 days apart

Timeline

• Start date: 2021-08-02
• Primary completion: 2022-03-11
• Completion: 2022-09-15
• First posted: 2021-06-23
• Last updated: 2022-12-05

Locations

1 site across 1 country: Switzerland