Phase-I Study to Evaluate the Safety and Immunogenicity of a Prophylactic pDNA Vaccine Candidate Against COVID-19 in Healthy Adults

Phase 1

Not yet recruiting

• Conditions: Safety; Immunization; Infection; Vaccine Reaction; Vaccine Adverse Reaction
• Interventions: Drug: S.opt.FL COVID-19 pDNA vaccine

• Registration Number: NCT05171946
• Lead Sponsor: Iman Almansour

Brief Summary

A pneumonia of unknown cause detected in Wuhan, China, was first reported in December 2019. On 08 January 2020, the pathogen causing this outbreak was identified as a novel coronavirus 2019. The outbreak was declared a Public Health Emergency of International Concern on 30 January 2020. On 12 February 2020, the virus was officially named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the WHO officially named the disease caused by SARS-CoV-2 as coronavirus disease 2019 (COVID-19). On 11 March 2020, the WHO upgraded the status of the COVID-19 outbreak from epidemic to pandemic, which is now spreading globally at high speed.

There are currently few licensed vaccines to prevent infection with SARS-CoV-2 or COVID-19 and the duration of response is unknown. Given the rapid transmission of COVID-19 and incidence of disease on a worldwide basis, the rapid development of effective vaccines with sufficient protection and duration of response is of utmost importance.

IAU has developed a thermally stable plasmid DNA (pDNA)-based vaccine candidate using a platform approach that enables the rapid development of vaccines against emerging viral diseases, including SARS-CoV-2. The pDNA vaccine developed by IAU is a synthetic, codon-optimized, encode either the full-length Spike (S) gene or S1 domain of SARS-CoV-2 as genes of interest. Here, we aim to test a synthetic, codon optimized pDNA encoding S.opt.FL as vaccine candidate against COVID-19.

A key advantage of pDNA vaccine is that multiple immunization can be used without the limitations of anti-vector responses.

This study is intended to investigate the safety, immunogenicity, and tolerbilty of this prophylactic vaccine against COVID-19 administered as intramuscular immunization (i.m.).

Detailed Description

Sever Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a newly emerging coronavirus that is known to cause worldwide public health crisis and an ongoing pandemic since February 2020 with 219 million cases and 4.5 million deaths as of September 2021 (1). The World Health Organization (WHO) has given the term Coronavirus Diseases 19 (COVID-19) to indicate the illness caused by SARS-CoV-2. Individuals infected SARS-CoV-2 can have wide ranges of symptoms that varies between mild to very severe (1,2).

Despite the existence of several COVID-19 vaccine that are approved under emergency use by EMA and FDA (2,3,4,5,6,7), there is a global demand for the manufacturing of sufficient vaccine to control the COVID-19 worldwide. In addition, there is a demand for the development and deployment of new COVID-19 vaccine that is generic and thermally stable for which the vaccine can be stored for a longer period, especially in countries that lacks the infrastructure capabilities to store the vaccine under freezing temperature.

Imam Abdulrahman Bin Faisal University (IAU) has developed an investigational prophylactic COVID-1 pDNA vaccine using a codon optimized spike gene of the SARS-CoV-2 (S.opt.FL). The developed pDNA vaccine possess several advantages; Unlike with mRNA vaccine platforms, pDNA is more stable. Therefore, cold-chain shipment and storage is not needed. Also, the chance for anti-vector immunity generated after immunization viral vector vaccine platform is omitted in pDNA vaccine platform. Importantly, the pDNA can stimulate humoral and cellular immune responses (9,10,11).

IAU COVID-19 vaccine Almansour-001 consists of a plasmid DNA (pDNA) carrying a synthetic, codon-optimized, gene insert that encodes spike (S) gene of COVID-19. The pDNA included in the study is (pVAX-1), an FDA approved plasmid for the application in clinical trials.

Preclinical study conducted at Imam Abdulrahman Bin Faisal University (IAU) have demonstrated that S.opt.FL and S1.opt are immunogenic in mice (8). The study investigated 3 doses versus 4 doses of DNA vaccine. The study demonstrated three doses S1.opt.FL elicited high bAB and nAB responses (8) as well as interferon-Gamma as an indicator of cellular immunity. Previous work on pDNA vaccines encoding the S gene of SARS-CoV, MERS-CoV, and SARS-CoV-2 have demonstrated that pDNA vaccine is safe and well tolerated (12,13,14,15).

The purpose of this clinical trial is to evaluate the safety and immunogenicity of 2 or 3 dose regimen of investigational pDNA vaccine encoding S.opt.FL gene inserted into pVAX1 plasmid (Almansour-001). Here, in this phase-I study, the pDNA vaccine candidate is administered intramuscularly (IM) by immunizing healthy adults (18-55 years). The S.opt.FL pDNA vaccine is evaluated in dose wise manner in three different cohorts (cohort 1: low dosage of pDNA vaccine "1 mg", cohort 2: middle dosage of pDNA vaccine "2 mg", cohort 3: high dosage of pDNA vaccine "4 mg")

Study Timeline

• Study First Submitted: 2021-12-07
• Study First Submitted QC: 2021-12-22
• Study First Posted: 2021-12-29
• Status Verified: 2022-10
• Last Update Submitted: 2022-10-16
• Last Update Posted: 2022-10-19
• Study Start: 2022-11-20
• Primary Completion: 2023-03-01
• Study Completion: 2023-07-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cohort 1	S.opt.FL COVID-19 pDNA vaccine	Low-Dose, 1mg, 3 doses 21 days apart
Cohort 2	S.opt.FL COVID-19 pDNA vaccine	Mid-Dose, 2 mg, 2 doses 21 days apart
Cohort 3	S.opt.FL COVID-19 pDNA vaccine	High-Dose, 4 mg, 2 doses 21 days apart

Primary Outcome Measures

Name	Time	Method
The percentage and frequency of study subjects reporting local reaction	Through 10 days after receiving each dose
The percentage and frequency of study subjects reporting systemic events (SAE)	From dose 1 through six months after last dose
Proportion of subjects with four folds increase in serum SARS-CoV-2 binding antibodies (anti-S, anti S1, and anti- RBD)	At baseline (pre-vaccination) and one month after last dose
GMT of the serum SARS-CoV-2 S neutralizing antibodies	At baseline (pre-vaccination) and one month after last dose
Proportion of subjects with four folds increase in serum SARS-CoV-2 neutralizing antibodies	At baseline (pre-vaccination) and one month after last dose
The percentage of study subjects reporting systematic reaction	Through 30 days after receiving each dose
The percentage and frequency of study subjects reporting adverse events (AE)	From dose 1 through six months after last dose
GMT of the serum SARS-CoV-2 binding antibodies (anti-S, anti S1, and anti-RBD)	At baseline (pre-vaccination) and one month after last dose

Secondary Outcome Measures

Name	Time	Method
GMT of the serum SARS-CoV-2 binding antibodies (anti-S, anti S1, and anti-RBD)	At baseline (pre-vaccination), three weeks after dose 1, three weeks after dose 2, one month after dose 3
Proportion of subjects with four folds increase in serum SARS-CoV-2 binding antibodies (anti-S, anti S1, and anti- RBD)	At baseline (pre-vaccination), three weeks after dose 1, three weeks after dose 2, one month after dose 3
Proportion of subjects with four folds increase in serum SARS-CoV-2 neutralizing antibodies	At baseline (pre-vaccination), three weeks after dose 1, three weeks after dose 2, one month after dose 3
GMT of the serum SARS-CoV-2 neutralizing antibodies	At baseline (pre-vaccination), three weeks after dose 1, three weeks after dose 2, one month after dose 3