INO-4201 as Booster in Healthy VSV-ZEBOV Vaccinees (Boost-EBOV)

Phase Ib, Placebo-controlled Randomized Clinical Trial to Evaluate the Safety, Tolerability and Immunogenicity of INO-4201 Followed by Electroporation as a Booster Vaccination in Healthy Volunteers Who Have Previously Received the VSV-ZEBOV Vaccine

Ebola virus disease (EVD) is a serious illness with a high fatality rate. Currently only one vaccine is available, VSV-ZEBOV/Ervebo; this vaccine is clinically effective and has been deployed as a preventive measure during recent Ebola outbreaks. The durability of protection afforded by this vaccine is unknown, however, and it is thought that a booster vaccination may be required to maintain immune responses. Recently, a synthetic DNA vaccine, INO-4201, was tested in humans and showed good immunogenicity and an enhanced safety profile.

This study aims to test whether the DNA-based candidate INO-4201 can be used as a booster in healthy volunteers previously vaccinated with VSV-ZEBOV.

Study Overview

• Status: Completed
• Conditions: Ebola Virus Disease
• Intervention / Treatment: Biological: INO-4201; Biological: Placebo

Detailed Description

This randomized placebo-controlled phase 1b trial will evaluate the safety, tolerability and immunogenicity of the DNA-based vaccine candidate INO-4201 in healthy adult volunteers who previously received a single injection of VSV-ZEBOV. These participants will be randomized to either INO-4201 or placebo, injected once intradermally (ID) followed by electroporation (EP) with the CELLECTRA2000 device. Volunteers will be observed for 1 hour after vaccination and will attend follow-up visits at the Clinical Trials Unit in the 24 weeks after injection (8 visits in all).

Primary outcome parameters are (i) the incidence of adverse events in relationship with INO-4201 from day 0 to 14, and (ii) geometric mean titers (GMT) of EBOV-GP-binding IgG antibodies at 4 weeks post-injection.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 1

Contacts and Locations

Study Locations

• Switzerland
  • Geneva, Switzerland, 1205
    • Geneva University Hospitals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Has provided written informed consent prior to screening
2. Males and females ≥ 18 years old
3. Previously vaccinated with a single dose of VSV-ZEBOV at any dose between 10^5 and 10^8 pfu more than 6 months prior to inclusion
4. Free of clinically significant health problems, as determined by pertinent medical history and clinical examination at study screening
5. Has an acceptable site for ID electroporation considering the deltoid and anterolateral quadriceps muscles
6. Is post-menopausal, or surgically sterile, or has a partner who is sterile, or uses a medically effective contraception with a failure rate of <1% per year when used consistently and correctly from screening until 6 months following last dose.

Exclusion Criteria:

1. Female volunteers who are pregnant or breastfeeding at screening or prior to dosing
2. Administration of an investigational compound either currently or within 30 days of Day 0
3. Prisoner or volunteers who are compulsorily detained (involuntary incarceration) for treatment of either a physical or psychiatric illness
4. Active drug or alcohol or substance abuse or dependence
5. Planned administration of another Ebola vaccine (including rVSV-ZEBOV and Ad26/MVA-BN-Filo vaccines) during the study period
6. Administration of a live vaccine in the 21 days or an inactivated vaccine in the 14 days before planned injection
7. Current or anticipated concomitant immunosuppressive therapy (excluding inhaled, topical skin and/or eye drop-containing corticosteroids, or low-dose methotrexate). Systemic corticosteroids must be discontinued at least 4 weeks prior to first dose.

Temporary exclusion criteria:

1. Acute disease at the time of randomization
2. Active skin lesions at the potential injection site
3. Temperature ≥38.0°C at the time of randomization
4. Recent receipt of a SARS-CoV-2 vaccine with final dose <4 weeks prior

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: INO-4201; One intradermal injection of INO-4201 followed by electroporation	Biological: INO-4201; One dose of 1 mg of INO-4201 in 0.1 ml injected intradermally followed by electroporation with CELLECTRA2000
Placebo Comparator: Placebo; One intradermal injection of normal saline followed by electroporation	Biological: Placebo; One dose of normal saline in 0.1 ml injected intradermally followed by electroporation with CELLECTRA2000

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events by systemic organ class, preferred term, severity and relationship to investigational product INO-4201 from day 0 to day 14.	Primary safety outcome	Days 0 - 14
Quantitative EBOV-GP-binding IgG antibody responses (GMTs as measured by ELISA) at 4 weeks after injection	Primary immunogenicity outcome	Days 0 - 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of solicited local and systemic reactogenicity signs and symptoms	Secondary safety outcome	Days 0 - 14
Occurrence of unsolicited adverse events	Secondary safety outcome	Days 0 - 28
Occurrence of serious adverse events (SAE)	Secondary safety outcome	Days 0 - 168
GMTs of EBOV-GP-binding antibodies as measured by ELISA	Secondary immunogenicity outcome	Weeks 2, 12, 24
GMTs of neutralizing antibodies	Secondary immunogenicity outcome	Weeks 2, 4, 12, 24

Collaborators and Investigators

• Sponsor: University of Geneva, Switzerland
• Collaborators: Inovio Pharmaceuticals; Defense Advanced Research Projects Agency; Global Urgent and Advanced Research and Development (GuardRX)

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2021
• Primary Completion (Actual): January 5, 2022
• Study Completion (Actual): May 11, 2022

Study Registration Dates

• First Submitted: May 25, 2021
• First Submitted That Met QC Criteria: May 25, 2021
• First Posted (Actual): May 28, 2021

Study Record Updates

• Last Update Posted (Actual): May 24, 2022
• Last Update Submitted That Met QC Criteria: May 22, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Infections; Mononegavirales Infections; Hemorrhagic Fevers, Viral; Filoviridae Infections; Virus Diseases; Hemorrhagic Fever, Ebola
• Other Study ID Numbers: 2020-02774

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes