A Study to Evaluate Safety & Immunogenicity of SARS-CoV-2 DNA Vaccine Delivered Intramuscularly Followed by Electroporation for COVID-19

NCT05102643 | Unknown Phase 1

• 1 other identifier: CTC2107
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

To investigate the safety and immunogenicity profile of of a novel and investigational SARS-CoV-2 DNA vaccine, which is delivered intramuscularly followed by electroporation to enhance vaccine penetration, as a potential prophylactic vaccine for current pandemic disease COVID-19.

Conditions

Covid19

Outcome Measures

Primary Outcomes (2)

• Reactogenicity

  Occurrence of solicited local events (pain, tenderness, redness, warmth, itch, swelling, induration) and solicited systemic events (fever, headache, malaise, myalgia, joint pain, nausea, vomiting, diarrhea, abdominal pain, chills and sweating) for a 14-day period after each vaccination

  Days 1 to 15 and Days 22 to 36

• Adverse Events

  Occurrence of unsolicited AEs, Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)

  Days 1 to 50(±3)

Secondary Outcomes (2)

• Binding Antibodies in Serum against SARS-CoV-2 RBD Measured by ELISA

  Day 1(pre-dose), 8(+1), 15(+1), 22(pre-dose), 29(+1), 36(+1) and 50(±3) visits

• Neutralizing Antibodies in Serum against Live SARS-CoV-2 Measured by Neutralization Assay

  Day 1(pre-dose), 8(+1), 15(+1), 22(pre-dose), 29(+1), 36(+1) and 50(±3) visits

Study Arms (2)

Test Product

EXPERIMENTAL

SARS-CoV-2 DNA Vaccine at 1mg and 2mg, 2 doses 3 weeks apart, intramuscular injection followed by electroporation

Biological: SARS-CoV-2 DNA Vaccine

Reference Product

PLACEBO COMPARATOR

Matching placebo, 2 doses 3 weeks apart, intramuscular injection followed by electroporation

Biological: Matching placebo

Interventions

SARS-CoV-2 DNA Vaccine BIOLOGICAL

A novel vaccine developed for prophylaxis of COVID-19 based on HKU's PD-1-based DNA vaccine platform. It encodes a recombinant antigen comprising a soluble human PD-1 domain (i.e. programmed cell death protein, a member of the Cluster of Differentiation 28 (CD28) family) and the receptor binding domain (RBD) of SARS-CoV-2 (i.e. the key viral entry element).

Test Product

Matching placebo BIOLOGICAL

Solution for intramuscular injection

Reference Product

Eligibility Criteria

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

You may qualify if:

• Informed Consent: The subject (or the subject's legally acceptable representative, if applicable) must be capable of giving written informed consent and, prior to the commencement of any study-specific procedure, must sign an ICF indicating the consent on the subject's voluntary participation in the study and compliance with the requirements and restrictions listed on the ICF.
• Gender and Age: Male or female, at the age of ≥ 18 and ≤ 55 on the day of signing the ICF.
• Body Weight and BMI: Body weight ≥ 50 kg and BMI ≥ 18.5 kg/m2 and \< 25 kg/m2 at screening and baseline.
• Medical Conditions or Diagnoses: Existence of all of the following medical conditions or diagnoses:
• Generally in good health with no clinically significant abnormality, as determined by medical history, physical examination, 12-lead ECG and clinical laboratory tests at screening and baseline;
• Normal vital signs at screening and baseline, as defined by:
• Body (tympanic) temperature ≤ 37.5oC;
• Resting pulse rate ≥ 50 and ≤ 100 bpm; and
• DBP ≥ 50 and ≤ 90 mmHg and SBP ≥ 90 and ≤ 140 mmHg.
• Contraception: Willingness and agreement to undertake measures to avoid pregnancy of the subject or the subject's sexual partner(s) as detailed below:
• A female subject who is a woman of childbearing potential (WOCBP) must be willing and agree to remain abstinent or practise at least one effective contraceptive method from at least 30 days prior to the first vaccination until 60 days after the second vaccination;
• A male subject (i) who is sexually active with a WOCBP (except who is permanently sterile by bilateral orchiectomy or vasectomy) must be willing and agree to remain abstinent or practise at least one effective contraceptive method from the first vaccination until 60 days after the second vaccination; and (ii) must be willing and agree to refrain from sperm donation during the aforesaid period.
• Breastfeeding: A female subject must be willing and agree to avoid engagement in breastfeeding at any time from the first vaccination until 60 days after the second vaccination.
• Blood Donation: Willingness and agreement to avoid blood donation from screening to the end of the period of participation in this study.

You may not qualify if:

• Medical History: History of any of the following diseases or conditions:
• COVID-19;
• SARS;
• Any significant respiratory diseases (e.g. COPD, asthma);
• Any significant cardiovascular disease (e.g. angina, cardiac arrhythmias);
• Blood dyscrasias or any significant disorder of coagulation;
• Any chronic liver disease (e.g. autoimmune hepatitis and cirrhosis);
• Any chronic infection (e.g. hepatitis B, hepatitis C and HIV);
• Any malignant neoplastic disease;
• Encephalopathy, neuropathy or unstable central nervous system (CNS) pathology;
• Any psychiatric disorder, psychotic disorder, major affective disorder or suicidal ideation;
• Any immunodeficiency or autoimmune disease;
• Any severe allergic reaction (e.g. anaphylaxis) to any vaccine or substance, which requires hospitalization or emergency medical care;
• History of alcohol or illicit drug abuse, or used any illicit drug within 6 months prior to screening.
• Medical Conditions or Diagnoses: Existence of any of the following medical conditions or diagnoses:

Sponsors & Collaborators

• The University of Hong Kong: lead
• Immuno Cure 3 Limited: collaborator

Study Sites (1)

HKU Phase 1 Clinical Trials Centre

Hong Kong, Hong Kong

RECRUITING

Related Publications (19)

• SARS-CoV-2 DNA Vaccine - Investigator's Brochure (Version 1.0, Dated 24-Sep-2021).

  BACKGROUND

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• Gallagher, K., Leick, M. B., Larson, R. C., Berger, T. R., Katsis, K., Yam, J. Y., Brini, G., Grauwet, K., MGH COVID-19 Collection & Processing Team, & Maus, M. V. (2021) 'SARS -CoV-2 T-cell immunity to variants of concern following vaccination', bioRxiv 2021.05.03.442455, Advance online publication. doi:10.1101/2021.05.03.442455.

  BACKGROUND

• Liu C, Lu Z, Xie Y, Guo Q, Geng F, Sun B, Wu H, Yu B, Wu J, Zhang H, Yu X, Kong W. Soluble PD-1-based vaccine targeting MUC1 VNTR and survivin improves anti-tumor effect. Immunol Lett. 2018 Aug;200:33-42. doi: 10.1016/j.imlet.2018.06.004. Epub 2018 Jun 9.

  PMID: 29894719 BACKGROUND

• Martin JE, Sullivan NJ, Enama ME, Gordon IJ, Roederer M, Koup RA, Bailer RT, Chakrabarti BK, Bailey MA, Gomez PL, Andrews CA, Moodie Z, Gu L, Stein JA, Nabel GJ, Graham BS. A DNA vaccine for Ebola virus is safe and immunogenic in a phase I clinical trial. Clin Vaccine Immunol. 2006 Nov;13(11):1267-77. doi: 10.1128/CVI.00162-06. Epub 2006 Sep 20.

  PMID: 16988008 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

• Poland GA, Ovsyannikova IG, Kennedy RB. SARS-CoV-2 immunity: review and applications to phase 3 vaccine candidates. Lancet. 2020 Nov 14;396(10262):1595-1606. doi: 10.1016/S0140-6736(20)32137-1. Epub 2020 Oct 13.

  PMID: 33065034 BACKGROUND

• Sallberg M, Frelin L, Ahlen G, Sallberg-Chen M. Electroporation for therapeutic DNA vaccination in patients. Med Microbiol Immunol. 2015 Feb;204(1):131-5. doi: 10.1007/s00430-014-0384-8. Epub 2014 Dec 23.

  PMID: 25535102 BACKGROUND

• Tan Z, Chiu MS, Yan CW, Wong YC, Huang H, Man K, Chen Z. Antimesothelioma Immunotherapy by CTLA-4 Blockade Depends on Active PD1-Based TWIST1 Vaccination. Mol Ther Oncolytics. 2020 Feb 8;16:302-317. doi: 10.1016/j.omto.2020.01.009. eCollection 2020 Mar 27.

  PMID: 32195318 BACKGROUND

• Tan Z, Zhou J, Cheung AK, Yu Z, Cheung KW, Liang J, Wang H, Lee BK, Man K, Liu L, Yuen KY, Chen Z. Vaccine-elicited CD8+ T cells cure mesothelioma by overcoming tumor-induced immunosuppressive environment. Cancer Res. 2014 Nov 1;74(21):6010-21. doi: 10.1158/0008-5472.CAN-14-0473. Epub 2014 Aug 14.

  PMID: 25125656 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.

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• Tebas P, Yang S, Boyer JD, Reuschel EL, Patel A, Christensen-Quick A, Andrade VM, Morrow MP, Kraynyak K, Agnes J, Purwar M, Sylvester A, Pawlicki J, Gillespie E, Maricic I, Zaidi FI, Kim KY, Dia Y, Frase D, Pezzoli P, Schultheis K, Smith TRF, Ramos SJ, McMullan T, Buttigieg K, Carroll MW, Ervin J, Diehl MC, Blackwood E, Mammen MP, Lee J, Dallas MJ, Brown AS, Shea JE, Kim JJ, Weiner DB, Broderick KE, Humeau LM. Safety and immunogenicity of INO-4800 DNA vaccine against SARS-CoV-2: A preliminary report of an open-label, Phase 1 clinical trial. EClinicalMedicine. 2021 Jan;31:100689. doi: 10.1016/j.eclinm.2020.100689. Epub 2020 Dec 24.

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• Wang P, Zheng M, Lau SY, Chen P, Mok BW, Liu S, Liu H, Huang X, Cremin CJ, Song W, Chen Y, Wong YC, Huang H, To KK, Chen Z, Xia N, Yuen KY, Chen H. Generation of DelNS1 Influenza Viruses: a Strategy for Optimizing Live Attenuated Influenza Vaccines. mBio. 2019 Sep 17;10(5):e02180-19. doi: 10.1128/mBio.02180-19.

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• Wong YC, Liu W, Yim LY, Li X, Wang H, Yue M, Niu M, Cheng L, Ling L, Du Y, Chen SMY, Cheung KW, Wang H, Tang X, Tang J, Zhang H, Song Y, Chakrabarti LA, Chen Z. Sustained viremia suppression by SHIVSF162P3CN-recalled effector-memory CD8+ T cells after PD1-based vaccination. PLoS Pathog. 2021 Jun 14;17(6):e1009647. doi: 10.1371/journal.ppat.1009647. eCollection 2021 Jun.

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• Vasan S, Hurley A, Schlesinger SJ, Hannaman D, Gardiner DF, Dugin DP, Boente-Carrera M, Vittorino R, Caskey M, Andersen J, Huang Y, Cox JH, Tarragona-Fiol T, Gill DK, Cheeseman H, Clark L, Dally L, Smith C, Schmidt C, Park HH, Kopycinski JT, Gilmour J, Fast P, Bernard R, Ho DD. In vivo electroporation enhances the immunogenicity of an HIV-1 DNA vaccine candidate in healthy volunteers. PLoS One. 2011;6(5):e19252. doi: 10.1371/journal.pone.0019252. Epub 2011 May 16.

  PMID: 21603651 BACKGROUND

• Vivarelli S, Falzone L, Torino F, Scandurra G, Russo G, Bordonaro R, Pappalardo F, Spandidos DA, Raciti G, Libra M. Immune-checkpoint inhibitors from cancer to COVID-19: A promising avenue for the treatment of patients with COVID-19 (Review). Int J Oncol. 2021 Feb;58(2):145-157. doi: 10.3892/ijo.2020.5159. Epub 2020 Dec 14.

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• Yu Z, Tan Z, Lee BK, Tang J, Wu X, Cheung KW, Lo NT, Man K, Liu L, Chen Z. Antigen spreading-induced CD8+T cells confer protection against the lethal challenge of wild-type malignant mesothelioma by eliminating myeloid-derived suppressor cells. Oncotarget. 2015 Oct 20;6(32):32426-38. doi: 10.18632/oncotarget.5856.

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• Zhou J, Cheung AK, Tan Z, Wang H, Yu W, Du Y, Kang Y, Lu X, Liu L, Yuen KY, Chen Z. PD1-based DNA vaccine amplifies HIV-1 GAG-specific CD8+ T cells in mice. J Clin Invest. 2013 Jun;123(6):2629-42. doi: 10.1172/JCI64704. Epub 2013 May 1.

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• Development and Licensure of Vaccines to Prevent COVID-19 Guidance for Industry. U.S. Department of Health and Human Services Food and Drug Administration Center for Biologics Evaluation and Research, June 2020

  BACKGROUND

Related Links

• Accessed on 07 January 2021
• Accessed on 28 July 2021
• Accessed on 28 July 2021

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

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

Study Officials

• Ivan Fan-ngai Hung

  The University of Hong Kong

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Volunteer Resource Centre

CONTACT

85296812309; ctcvrc@hku.hk

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Subjects will be enrolled into 2 cohorts and each subject will receive 2 vaccinations at one of the 2 dose levels or matching placebo. Each subject will only participate in one cohort. A Safety Review Committee (SRC) will be set up to review safety data and make decision on dose escalation.

Study Record Dates

• First Submitted: October 29, 2021
• First Posted: November 1, 2021
• Study Start: November 18, 2021
• Primary Completion: June 1, 2022
• Study Completion: December 1, 2022
• Last Updated: January 27, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)