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

NCT05171946 | Unknown Phase 1 DMC

• 1 other identifier: IAU-1-001-2021
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

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.).

Conditions

Safety; Vaccine Reaction; Vaccine Adverse Reaction; Immunization; Infection

Keywords

Vaccine; COVID-19; SARS-CoV-2; pDNA vaccine; Phase-I; Prophylactic; Safety; Immunogenicity

Outcome Measures

Primary Outcomes (8)

• The percentage and frequency of study subjects reporting local reaction

  Through 10 days after receiving each 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

• The percentage and frequency of study subjects reporting systemic events (SAE)

  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

• 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

Secondary Outcomes (4)

• 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

• 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

• 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

Other Outcomes (3)

• GMT of SARS-CoV-2 S specific binding antibodies against SARS-CoV-2 variants of concern (Alpha, Beta, Gamma, and Omicron)

  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)

  At baseline (pre-vaccination) and one month after last dose

• Evaluation of intracellular cytokine responses

  At baseline (pre-vaccination), three weeks after dose 1, three weeks after dose 2, one month after dose 3

Study Arms (3)

Cohort 1

EXPERIMENTAL

Low-Dose, 1mg, 3 doses 21 days apart

Drug: S.opt.FL COVID-19 pDNA vaccine

Cohort 2

EXPERIMENTAL

Mid-Dose, 2 mg, 2 doses 21 days apart

Drug: S.opt.FL COVID-19 pDNA vaccine

Cohort 3

EXPERIMENTAL

High-Dose, 4 mg, 2 doses 21 days apart

Drug: S.opt.FL COVID-19 pDNA vaccine

Interventions

S.opt.FL COVID-19 pDNA vaccine DRUG

Low-Dose: (1mg) level

Also known as: Almansour-001

Cohort 1

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female participants between the age of 18 to 55 years (inclusive) at the time of enrollment.
• Healthy participants as determined by the medical history, physical examination, clinical verification by the investigator.
• Participant who are committed to comply with planned scheduled visits, vaccination, laboratory tests, and any other procedures.
• Participants who received 2 doses of an approved mRNA COVID-19 vaccine at least 4 months prior to enrollment.
• 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.
• 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.
• Willing to sign the informed consent which includes all the requirements and restrictions listed in the informed consent and the protocol.

You may not qualify if:

• Participant with known infection with Hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV).
• Individuals with current infection and diagnosis with COVID-19 documented by PCR nasal swab test.
• Individuals who received an authorized mRNA COVID-19 vaccine within the past 4 months of first study drug administration.
• Individuals who received only one dose of a COVID-19 vaccine.
• Individuals working in facility with high probability of infection with SARS-CoV-2 such as health workers in hospitals.
• History of adverse reaction associated with vaccines and/or severe allergic reaction to any component of the study intervention.
• Individuals under immunosuppressive therapy.
• 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.
• 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

Sponsors & Collaborators

• Iman Almansour: lead
• ICON plc: collaborator

Related Publications (15)

• Viner RM, Ward JL, Hudson LD, Ashe M, Patel SV, Hargreaves D, Whittaker E. Systematic review of reviews of symptoms and signs of COVID-19 in children and adolescents. Arch Dis Child. 2021 Jul 19;106(8):802-807. doi: 10.1136/archdischild-2020-320972.

  PMID: 33334728 BACKGROUND

• Chen X, Laurent S, Onur OA, Kleineberg NN, Fink GR, Schweitzer F, Warnke C. A systematic review of neurological symptoms and complications of COVID-19. J Neurol. 2021 Feb;268(2):392-402. doi: 10.1007/s00415-020-10067-3. Epub 2020 Jul 20.

  PMID: 32691236 BACKGROUND

• Oliver SE, Gargano JW, Marin M, Wallace M, Curran KG, Chamberland M, McClung N, Campos-Outcalt D, Morgan RL, Mbaeyi S, Romero JR, Talbot HK, Lee GM, Bell BP, Dooling K. The Advisory Committee on Immunization Practices' Interim Recommendation for Use of Moderna COVID-19 Vaccine - United States, December 2020. MMWR Morb Mortal Wkly Rep. 2021 Jan 1;69(5152):1653-1656. doi: 10.15585/mmwr.mm695152e1.

  PMID: 33382675 BACKGROUND

• Oliver SE, Gargano JW, Marin M, Wallace M, Curran KG, Chamberland M, McClung N, Campos-Outcalt D, Morgan RL, Mbaeyi S, Romero JR, Talbot HK, Lee GM, Bell BP, Dooling K. The Advisory Committee on Immunization Practices' Interim Recommendation for Use of Pfizer-BioNTech COVID-19 Vaccine - United States, December 2020. MMWR Morb Mortal Wkly Rep. 2020 Dec 18;69(50):1922-1924. doi: 10.15585/mmwr.mm6950e2.

  PMID: 33332292 BACKGROUND

• Roncati L, Roncati M. Emergency use authorization (EUA), conditional marketing authorization (CMA), and the precautionary principle at the time of COVID-19 pandemic. J Public Health Policy. 2021 Sep;42(3):518-521. doi: 10.1057/s41271-021-00299-6. Epub 2021 Jul 27. No abstract available.

  PMID: 34316006 BACKGROUND

• MacNeil JR, Su JR, Broder KR, Guh AY, Gargano JW, Wallace M, Hadler SC, Scobie HM, Blain AE, Moulia D, Daley MF, McNally VV, Romero JR, Talbot HK, Lee GM, Bell BP, Oliver SE. Updated Recommendations from the Advisory Committee on Immunization Practices for Use of the Janssen (Johnson & Johnson) COVID-19 Vaccine After Reports of Thrombosis with Thrombocytopenia Syndrome Among Vaccine Recipients - United States, April 2021. MMWR Morb Mortal Wkly Rep. 2021 Apr 30;70(17):651-656. doi: 10.15585/mmwr.mm7017e4.

  PMID: 33914723 BACKGROUND

• Krause PR, Gruber MF. Emergency Use Authorization of Covid Vaccines - Safety and Efficacy Follow-up Considerations. N Engl J Med. 2020 Nov 5;383(19):e107. doi: 10.1056/NEJMp2031373. Epub 2020 Oct 16. No abstract available.

  PMID: 33064383 BACKGROUND

• Almansour I, Macadato NC, Alshammari T. Immunogenicity of Multiple Doses of pDNA Vaccines against SARS-CoV-2. Pharmaceuticals (Basel). 2021 Jan 6;14(1):39. doi: 10.3390/ph14010039.

  PMID: 33419184 BACKGROUND

• Yang B, Jeang J, Yang A, Wu TC, Hung CF. DNA vaccine for cancer immunotherapy. Hum Vaccin Immunother. 2014;10(11):3153-64. doi: 10.4161/21645515.2014.980686.

  PMID: 25625927 BACKGROUND

• Liu MA. A Comparison of Plasmid DNA and mRNA as Vaccine Technologies. Vaccines (Basel). 2019 Apr 24;7(2):37. doi: 10.3390/vaccines7020037.

  PMID: 31022829 BACKGROUND

• Lee LYY, Izzard L, Hurt AC. A Review of DNA Vaccines Against Influenza. Front Immunol. 2018 Jul 9;9:1568. doi: 10.3389/fimmu.2018.01568. eCollection 2018.

  PMID: 30038621 BACKGROUND

• Modjarrad K, Roberts CC, Mills KT, Castellano AR, Paolino K, Muthumani K, Reuschel EL, Robb ML, Racine T, Oh MD, Lamarre C, Zaidi FI, Boyer J, Kudchodkar SB, Jeong M, Darden JM, Park YK, Scott PT, Remigio C, Parikh AP, Wise MC, Patel A, Duperret EK, Kim KY, Choi H, White S, Bagarazzi M, May JM, Kane D, Lee H, Kobinger G, Michael NL, Weiner DB, Thomas SJ, Maslow JN. Safety and immunogenicity of an anti-Middle East respiratory syndrome coronavirus DNA vaccine: a phase 1, open-label, single-arm, dose-escalation trial. Lancet Infect Dis. 2019 Sep;19(9):1013-1022. doi: 10.1016/S1473-3099(19)30266-X. Epub 2019 Jul 24.

  PMID: 31351922 BACKGROUND

• Tebas P, Roberts CC, Muthumani K, Reuschel EL, Kudchodkar SB, Zaidi FI, White S, Khan AS, Racine T, Choi H, Boyer J, Park YK, Trottier S, Remigio C, Krieger D, Spruill SE, Bagarazzi M, Kobinger GP, Weiner DB, Maslow JN. Safety and Immunogenicity of an Anti-Zika Virus DNA Vaccine - Preliminary Report. N Engl J Med. 2017 Oct 4:10.1056/NEJMoa1708120. doi: 10.1056/NEJMoa1708120. Online ahead of print.

  PMID: 28976850 BACKGROUND

• Tebas P, Kraynyak KA, Patel A, Maslow JN, Morrow MP, Sylvester AJ, Knoblock D, Gillespie E, Amante D, Racine T, McMullan T, Jeong M, Roberts CC, Park YK, Boyer J, Broderick KE, Kobinger GP, Bagarazzi M, Weiner DB, Sardesai NY, White SM. Intradermal SynCon(R) Ebola GP DNA Vaccine Is Temperature Stable and Safely Demonstrates Cellular and Humoral Immunogenicity Advantages in Healthy Volunteers. J Infect Dis. 2019 Jul 2;220(3):400-410. doi: 10.1093/infdis/jiz132.

  PMID: 30891607 BACKGROUND

• Muthumani K, Falzarano D, Reuschel EL, Tingey C, Flingai S, Villarreal DO, Wise M, Patel A, Izmirly A, Aljuaid A, Seliga AM, Soule G, Morrow M, Kraynyak KA, Khan AS, Scott DP, Feldmann F, LaCasse R, Meade-White K, Okumura A, Ugen KE, Sardesai NY, Kim JJ, Kobinger G, Feldmann H, Weiner DB. A synthetic consensus anti-spike protein DNA vaccine induces protective immunity against Middle East respiratory syndrome coronavirus in nonhuman primates. Sci Transl Med. 2015 Aug 19;7(301):301ra132. doi: 10.1126/scitranslmed.aac7462.

  PMID: 26290414 BACKGROUND

MeSH Terms

Conditions

Infections; COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Iman Almansour, Ph.D.

CONTACT

0534888861; ikalmansour@iau.edu.sa

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Trial Manager

Study Record Dates

• First Submitted: December 7, 2021
• First Posted: December 29, 2021
• Study Start: November 20, 2022
• Primary Completion: March 1, 2023
• Study Completion: July 1, 2023
• Last Updated: October 19, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share