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

October 16, 2022 updated by: Iman Almansour

Phase-I, Single Center, Randomized, Dosage Finding Study, to Evaluate the Safety, Tolerability, and Immunogenicity of a Prophylactic COVID-19 pDNA Vaccine After Multiple Ascending Doses in Healthy Adults

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.).

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion criteria

Study participants should meet ALL the below inclusion criteria to be eligible for the study:

  1. Male or female participants between the age of 18 to 55 years (inclusive) at the time of enrollment.
  2. Healthy participants as determined by the medical history, physical examination, clinical verification by the investigator.
  3. Participant who are committed to comply with planned scheduled visits, vaccination, laboratory tests, and any other procedures.
  4. Participants who received 2 doses of an approved mRNA COVID-19 vaccine at least 4 months prior to enrollment.
  5. Female subjects must have used an acceptable contraceptive method for at least 60 days prior to receiving the first dose of the investigational vaccine and should continue using contraception for at least 1 month after receiving the last dose of the investigational vaccine.
  6. Male subjects able to father children, and sexually active with a female partner who is able to bear children must be willing to use (or have his female partner use) an acceptable contraceptive method from the time they receive the first dose of the study vaccine until at least 1 month after the last dose of study vaccine.
  7. Willing to sign the informed consent which includes all the requirements and restrictions listed in the informed consent and the protocol.

Exclusion criteria

Study participants should meet NONE of the exclusion criteria listed below:

  1. Participant with known infection with Hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV).
  2. Individuals with current infection and diagnosis with COVID-19 documented by PCR nasal swab test.
  3. Individuals who received an authorized mRNA COVID-19 vaccine within the past 4 months of first study drug administration.
  4. Individuals who received only one dose of a COVID-19 vaccine.
  5. Individuals working in facility with high probability of infection with SARS-CoV-2 such as health workers in hospitals.
  6. History of adverse reaction associated with vaccines and/or severe allergic reaction to any component of the study intervention.
  7. Individuals under immunosuppressive therapy.
  8. Individuals receiving treatment or medications that can adherently affect the immune system in the last 90 days, including but not limited to: interferon, immunoglobin, immunomodulators, epinephrine injector, cytotoxic drug.

  9. Individuals diagnosed any diseases that is/are associated with sever COVID-19, including the following factors:

    • Diabetes
    • Hypertension
    • Asthma
    • BMI more than 30 kg/m2
    • Pregnant or lactating women.
    • Chronic pulmonary disease
    • Chronic liver diseases
    • Chronic renal diseases
  10. Individuals with known or suspected immunological disorders, including, autoimmune disease and diabetes mellitus.
  11. Individuals with current or previous neurological disorders, such as seizure or Gillian-Barre syndrome.
  12. Individuals with psychiatric disorder or cognitive impairment.
  13. Individuals with bleeding disorder or other conditions associated with prolonged bleeding time.
  14. Individuals with clinically significant abnormal safety laboratory results at screening in the opinion of the investigator.
  15. Individuals receiving or planning to receive non-study vaccine 30 days prior to study enrollment.
  16. Individuals receiving or donating blood or blood components 60 days prior to study enrollment.
  17. Individuals participating in a clinical trial with an investigational vaccine, treatment, or device 30 days prior to study enrollment.
  18. Individuals intending to participate in another clinical trial while being enrolled in this study.
  19. Individuals with history of alcohol or drug addiction.
  20. Individual with other condition that may interfere with the health or the participants or that interfere with study's primary or secondary objectives.
  21. Female participants who are pregnant, plan to get pregnant or are breast feeding.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: SINGLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Cohort 1
Low-Dose, 1mg, 3 doses 21 days apart
Drug: S.opt.FL COVID-19 pDNA vaccine
Low-Dose: (1mg) level
Other Names:
  • Almansour-001
Drug: S.opt.FL COVID-19 pDNA vaccine
Mid-Dose: (2mg) level
Other Names:
  • Almansour-001
Drug: S.opt.FL COVID-19 pDNA vaccine
High-Dose: (4mg) level
Other Names:
  • Almansour-001
EXPERIMENTAL: Cohort 2
Mid-Dose, 2 mg, 2 doses 21 days apart
Drug: S.opt.FL COVID-19 pDNA vaccine
Low-Dose: (1mg) level
Other Names:
  • Almansour-001
Drug: S.opt.FL COVID-19 pDNA vaccine
Mid-Dose: (2mg) level
Other Names:
  • Almansour-001
Drug: S.opt.FL COVID-19 pDNA vaccine
High-Dose: (4mg) level
Other Names:
  • Almansour-001
EXPERIMENTAL: Cohort 3
High-Dose, 4 mg, 2 doses 21 days apart
Drug: S.opt.FL COVID-19 pDNA vaccine
Low-Dose: (1mg) level
Other Names:
  • Almansour-001
Drug: S.opt.FL COVID-19 pDNA vaccine
Mid-Dose: (2mg) level
Other Names:
  • Almansour-001
Drug: S.opt.FL COVID-19 pDNA vaccine
High-Dose: (4mg) level
Other Names:
  • Almansour-001

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Time Frame
GMT of the serum SARS-CoV-2 binding antibodies (anti-S, anti S1, and anti-RBD)
Time Frame: At baseline (pre-vaccination), three weeks after dose 1, three weeks after dose 2, one month after dose 3
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)
Time Frame: At baseline (pre-vaccination), three weeks after dose 1, three weeks after dose 2, one month after dose 3
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
Time Frame: At baseline (pre-vaccination), three weeks after dose 1, three weeks after dose 2, one month after dose 3
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
Time Frame: At baseline (pre-vaccination), three weeks after dose 1, three weeks after dose 2, one month after dose 3
At baseline (pre-vaccination), three weeks after dose 1, three weeks after dose 2, one month after dose 3

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
GMT of SARS-CoV-2 S specific binding antibodies against SARS-CoV-2 variants of concern (Alpha, Beta, Gamma, and Omicron)
Time Frame: At baseline (pre-vaccination) and one month after last dose
V-PLEX SARS-CoV-2 Panel 28 IgG
At baseline (pre-vaccination) and one month after last dose
GMT of SARS-CoV-2 S specific neutralizing antibodies against SARS-CoV-2 variants of concern (Alpha, Beta, Gamma, and Omicron)
Time Frame: At baseline (pre-vaccination) and one month after last dose
V-PLEX SARS-CoV-2 Panel 28 ACE2
At baseline (pre-vaccination) and one month after last dose
Evaluation of intracellular cytokine responses
Time Frame: At baseline (pre-vaccination), three weeks after dose 1, three weeks after dose 2, one month after dose 3
Analysis of post-culture PBMCs under 3 conditions with the following panel:IFN-Gamma, TNF, IL-2, IL-4, IL-13 (V-Plex Viral Panel human Kit)
At baseline (pre-vaccination), three weeks after dose 1, three weeks after dose 2, one month after dose 3

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Iman Almansour

Collaborators

ICON plc

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ANTICIPATED)

November 20, 2022

Primary Completion (ANTICIPATED)

March 1, 2023

Study Completion (ANTICIPATED)

July 1, 2023

Study Registration Dates

First Submitted

December 7, 2021

First Submitted That Met QC Criteria

December 22, 2021

First Posted (ACTUAL)

December 29, 2021

Study Record Updates

Last Update Posted (ACTUAL)

October 19, 2022

Last Update Submitted That Met QC Criteria

October 16, 2022

Last Verified

October 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IAU-1-001-2021

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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