Clinical trial NCT04944368: Phase II Clinical Trial of CinnaGen COVID-19 Vaccine (SpikoGen)
Official title: A Phase II, Randomized, Two-armed, Double-blind, Placebo-controlled Trial to Evaluate the Safety, Tolerability, and Immunogenicity of an Adjuvanted Recombinant SARS-CoV-2 Spike (S) Protein Subunit Vaccine Candidate (SpikoGen)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Covid19
Keywords: COVID-19
SARS-COV-2
Recombinant protein
Spike
Advax-SM
Advax
Vaccine
Adjuvant
Lead sponsor: Cinnagen
Sponsor class: INDUSTRY
Collaborators: name: Vaxine Pty Ltd
First posted: 2021-06-29
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This is a phase II, randomized, two-armed, double-blind, placebo-controlled trial designed to evaluate the safety, tolerability, and immunogenicity of a candidate adjuvanted recombinant SARS-CoV-2 spike (S) protein subunit vaccine (SpikoGen) produced by CinnaGen Co. 400 adult individuals receive either SARS-CoV-2 recombinant spike protein (25 µg) with Advax-SM adjuvant (15 mg) or saline placebo in a 3:1 ratio. The injection is given in two doses with a 21-day interval in the deltoid muscle of the non-dominant arm. The randomization was stratified by age (\<65 or ≥65) and health conditions of potential risk for severe COVID-19. Participants will be visited at two weeks and will be followed up for six months after the second dose of the study intervention.

Study hypotheses include:

1. The adjuvanted COVID-19 vaccine candidate is safe and tolerable in adult subjects.
2. The adjuvanted COVID-19 vaccine candidate induces strong immunogenicity against SARS-CoV-2 in adult subjects.


Eligibility criteria: Inclusion Criteria:

* Male or female ≥18 years
* Willing and able to comply with all study requirements, including scheduled visits, interventions, and laboratory tests
* Healthy adults or adults in a stable medical condition, defined as not being hospitalized within 3 months prior to the screening visit
* Females must not be pregnant or breastfeeding

Exclusion Criteria:

* Subjects with signs of active SARS-COV-2 infection at the screening visit.
* Subjects with body temperature of 38 degrees Celsius or greater at the screening visit or within 72 hours prior to the screening visit.
* Subjects with a history of any progressive or severe neurological disorders, seizure, or Guillain-Barre syndrome.
* Subjects who receive immunosuppressive or cytotoxic medications.
* Female Subjects who are pregnant or breastfeeding or have planned to become pregnant during the study period.
* Subjects who have a history of severe allergic reactions (e.g., anaphylaxis) to the study vaccine, any components of the study interventions, or any pharmaceutical products.
* Subjects who have received any other investigational products within 30 days prior to the screening visit or intend to participate in any other clinical studies during the period of this study.
* Subjects who have been vaccinated with any vaccine or vaccine candidate against SARS-CoV-2.
* Subjects who have received any vaccines within 28 days prior to the screening visit or intend to receive any vaccines up to 14 days after the second dose of the study injection.
* Subjects who have any known bleeding disorders or, in the investigator's opinion, have any contraindications for an intramuscular injection.
* Subjects who have received any blood, plasma, or immunoglobulin products from 90 days prior to the screening visit or intend to receive during the study period.
* Subjects with any condition that may increase the risk of participating in the study or may interfere with the evaluation of the primary endpoints of the study in the investigator's opinion.
* Subjects who have donated ≥450 mL of blood or blood products within 28 days prior to the screening visit.

Primary outcomes:
measure: Incidence of solicited adverse events
timeFrame: For 7 days after each dose
measure: Incidence of unsolicited adverse events
timeFrame: For 28 days after each dose
measure: Percentage of participants with seroconversion for S1 binding IgG antibodies after the first injection
timeFrame: 21 days after the first dose (on the day of the second dose)
measure: Percentage of participants with seroconversion for S1 binding IgG antibodies after the second injection
timeFrame: 14 days after the second dose
measure: Change in geometric mean concentration (GMC) for S1 binding IgG antibodies from baseline to 21 days after the first injection
timeFrame: On the day of the first dose and 21 days after the first dose (on the day of the second dose)
measure: Change in geometric mean concentration (GMC) for S1 binding IgG antibodies from baseline to 14 days after the second injection
timeFrame: On the day of the first dose and 14 days after the second dose
Secondary outcomes:
measure: Percentage of participants with seroconversion for SARS-CoV-2 neutralizing antibodies after the first injection
timeFrame: 21 days after the first dose (on the day of the second dose)
measure: Percentage of participants with seroconversion for SARS-CoV-2 neutralizing antibodies after the first injection
timeFrame: 21 days after the first dose (on the day of the second dose)
measure: Percentage of participants with seroconversion for SARS-CoV-2 neutralizing antibodies after the second injection
timeFrame: 14 days after the second dose
measure: Percentage of participants with seroconversion for SARS-CoV-2 neutralizing antibodies after the second injection
timeFrame: 14 days after the second dose
measure: Percentage of participants with seroconversion for receptor-binding domain (RBD) binding IgA antibodies after the first injection
timeFrame: 21 days after the first dose (on the day of the second dose)
measure: Percentage of participants with seroconversion for receptor-binding domain (RBD) binding IgA antibodies after the second injection
timeFrame: 14 days after the second dose
measure: Percentage of participants with seroconversion for S1 binding IgA antibodies after the first injection
timeFrame: 21 days after the first dose (on the day of the second dose)
measure: Percentage of participants with seroconversion for S1 binding IgA antibodies after the second injection
timeFrame: 14 days after the second dose
measure: Percentage of participants with seroconversion for receptor-binding domain (RBD) binding IgG antibodies after the first injection
timeFrame: 21 days after the first dose (on the day of the second dose)
measure: Percentage of participants with seroconversion for receptor-binding domain (RBD) binding IgG antibodies after the second injection
timeFrame: 14 days after the second dose
measure: Change in geometric mean concentration (GMC) for receptor-binding domain (RBD) binding IgG antibodies from baseline to 21 days after the first injection
timeFrame: On the day of the first dose and 21 days after the first dose (on the day of the second dose)
measure: Change in geometric mean concentration (GMC) for receptor-binding domain (RBD) binding IgG antibodies from baseline to 14 days after the second injection
timeFrame: On the day of the first dose and 14 days after the second dose
measure: Geometric mean fold rise (GMFR) for S1 binding IgG antibodies after the first injection
timeFrame: 21 days after the first dose (on the day of the second dose)
measure: Geometric mean fold rise (GMFR) for S1 binding IgG antibodies after the second injection
timeFrame: 14 days after the second dose
measure: Geometric mean fold rise (GMFR) for receptor-binding domain (RBD) binding IgG antibodies after the first injection
timeFrame: 21 days after the first dose (on the day of the second dose)
measure: Geometric mean fold rise (GMFR) for receptor-binding domain (RBD) binding IgG antibodies after the second injection
timeFrame: 14 days after the second dose
measure: Geometric mean fold rise (GMFR) for SARS-CoV-2 neutralizing antibodies after the first injection
timeFrame: 21 days after the first dose (on the day of the second dose)
measure: Geometric mean fold rise (GMFR) for SARS-CoV-2 neutralizing antibodies after the second injection
timeFrame: 14 days after the second dose
measure: Change in geometric mean concentration (GMC) for SARS-CoV-2 neutralizing antibodies from baseline to 21 days after the first injection
timeFrame: On the day of the first dose and 21 days after the first dose (on the day of the second dose)
measure: Change in geometric mean concentration (GMC) for SARS-CoV-2 neutralizing antibodies from baseline to 14 days after the second injection
timeFrame: On the day of the first dose and 14 days after the second dose
measure: Change in geometric mean concentration (GMC) for S1 binding IgA antibodies from baseline to 21 days after the first injection
timeFrame: On the day of the first dose and 21 days after the first dose (on the day of the second dose)
measure: Change in geometric mean concentration (GMC) for S1 binding IgA antibodies from baseline to 14 days after the second injection
timeFrame: On the day of the first dose and 14 days after the second dose
measure: Geometric mean fold rise (GMFR) for S1 binding IgA antibodies after the first injection
timeFrame: 21 days after the first dose (on the day of the second dose)
measure: Geometric mean fold rise (GMFR) for S1 binding IgA antibodies after the second injection
timeFrame: 14 days after the second dose
measure: Incidence of serious adverse events (SAEs) and suspected unexpected serious adverse reaction (SUSARs)
timeFrame: For 6 months after the second dose
measure: Change in T-cell proliferation responses from baseline to 21 days after the first injection
timeFrame: On the day of the first dose and 21 days after the first dose (on the day of the second dose)
measure: Change in T-cell proliferation responses from baseline to 14 days after the second injection
timeFrame: On the day of the first dose and 14 days after the second dose
measure: Change in T-cell IFN-γ secretion from baseline to 21 days after the first injection
timeFrame: On the day of the first dose and 21 days after the first dose (on the day of the second dose)
measure: Change in T-cell IFN-γ secretion from baseline to 14 days after the second injection
timeFrame: On the day of the first dose and 14 days after the second dose
Other outcomes:
Locations:
city: Tehran
country: Iran, Islamic Republic of
facility: Espinas Palace Hotel
Study officials:
affiliation: Shahid Beheshti University of Medical Sciences
name: Payam Tabarsi, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tabarsi P, Anjidani N, Shahpari R, Mardani M, Sabzvari A, Yazdani B, Roshanzamir K, Bayatani B, Taheri A, Petrovsky N, Li L, Barati S. Safety and immunogenicity of SpikoGen(R), an Advax-CpG55.2-adjuvanted SARS-CoV-2 spike protein vaccine: a phase 2 randomized placebo-controlled trial in both seropositive and seronegative populations. Clin Microbiol Infect. 2022 Sep;28(9):1263-1271. doi: 10.1016/j.cmi.2022.04.004. Epub 2022 Apr 15.