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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05171946
Recruitment Status : Not yet recruiting
First Posted : December 29, 2021
Last Update Posted : December 29, 2021
Sponsor:
Collaborator:
ICON plc
Information provided by (Responsible Party):
Imam Abdulrahman Bin Faisal University

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.).


Condition or disease Intervention/treatment Phase
Safety Vaccine Reaction Vaccine Adverse Reaction Immunization; Infection Drug: S.opt.FL COVID-19 pDNA vaccine Phase 1

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 3 doses of investigational pDNA vaccine encoding S.opt.FL gene inserted into pVAX1 plasmid. 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")

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: Phase-I, Single Center, Randomized, Observer Blind, Dosage Finding Study, to Evaluate the Safety, Tolerability, and Immunogenicity of a Prophylactic COVID-19 pDNA Vaccine After Multiple Ascending Doses in Healthy Adults
Estimated Study Start Date : February 1, 2022
Estimated Primary Completion Date : July 1, 2022
Estimated Study Completion Date : February 1, 2023

Resource links provided by the National Library of Medicine


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 Name: Almansour-001

Experimental: Cohort 2
Mid-Dose, 2 mg, 3 doses 21 days apart
Drug: S.opt.FL COVID-19 pDNA vaccine
Mid-Dose: (2mg) level
Other Name: Almansour-001

Experimental: Cohort 3
High-Dose, 4 mg, 3 doses 21 days apart
Drug: S.opt.FL COVID-19 pDNA vaccine
High-Dose: (4mg) level
Other Name: Almansour-001




Primary Outcome Measures :
  1. The percentage and frequency of study subjects reporting local reaction [ Time Frame: Through 10 days after receiving each dose ]
  2. The percentage of study subjects reporting systematic reaction [ Time Frame: Through 30 days after receiving each dose ]
  3. The percentage and frequency of study subjects reporting adverse events (AE) [ Time Frame: From dose 1 through six months after last dose ]
  4. The percentage and frequency of study subjects reporting systemic events (SAE) [ Time Frame: From dose 1 through six months after last dose ]
  5. 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 ]
  6. 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 ]
  7. GMT of the serum SARS-CoV-2 S neutralizing antibodies [ Time Frame: At baseline (pre-vaccination) and one month after last dose ]
  8. 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 ]

Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]
  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 ]
  4. 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 ]

Other Outcome Measures:
  1. 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 ]
  2. 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 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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 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. Committed 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 previous infection and diagnosis with COVID-19.
  3. Individuals with previous vaccination with any COVID-19 vaccine.
  4. Individuals working in facility with high probability of infection with SARS-CoV-2.
  5. History of adverse reaction associated with vaccines and/or severe allergic reaction to any component of the study intervention.
  6. Individuals under immunosuppressive therapy.
  7. 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.
  8. 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
  9. Individuals with known or suspected immunological disorders, including, autoimmune disease and diabetes mellitus.
  10. Individuals with current or previous neurological disorders, such as seizure or Gillian-Barre syndrome.
  11. Individuals with psychiatric disorder or cognitive impairment.
  12. Individuals with bleeding disorder or other conditions associated with prolonged bleeding time.
  13. Individuals with abnormal safety laboratory screening.
  14. Individuals receiving or planning to receive non-study vaccine 30 days prior to study enrollment.
  15. Individuals receiving or donating blood or blood components 60 days prior to study enrollment.
  16. Individuals participating in a clinical trial with an investigational vaccine, treatment, or device 30 days prior to study enrollment.
  17. Individuals intend to participate in clinical trial during the time to participate in the study.
  18. Individuals with history of alcohol or drug addiction.
  19. Individual with other condition that may interfere with the health or the participants or that interfere with study's primary or secondary objectives.
  20. Female participants whom are breast feeding

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05171946


Contacts
Layout table for location contacts
Contact: Iman Almansour, Ph.D. 0534888861 ikalmansour@iau.edu.sa

Sponsors and Collaborators
Imam Abdulrahman Bin Faisal University
ICON plc
Publications:

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Responsible Party: Imam Abdulrahman Bin Faisal University
ClinicalTrials.gov Identifier: NCT05171946    
Other Study ID Numbers: IAU-1-001-2021
First Posted: December 29, 2021    Key Record Dates
Last Update Posted: December 29, 2021
Last Verified: December 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Imam Abdulrahman Bin Faisal University:
Vaccine
COVID-19
SARS-CoV-2
pDNA vaccine
Phase-I
Prophylactic
Safety
Immunogenicity
Additional relevant MeSH terms:
Layout table for MeSH terms
COVID-19
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Vaccines
Immunologic Factors
Physiological Effects of Drugs