Clinical trial NCT06205524: A Study to Evealuate Safety and Immunogenicity of TI-0010 SARS-CoV-2 Vaccine in Healthy Adults
Official title: An Exploratory, Randomized, Double-Blind, Dose-Ranging Study to Evaluate the Safety and Immunogenicity of TI-0010 Vaccine to Prevent COVID-19 Caused by SARS-CoV-2 in Healthy Adults Aged 18-59 Years
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: COVID-19
COVID-19 Immunisation
Lead sponsor: National Drug Clinical Trial Institute of the Second Affiliated Hospital of Bengbu Medical College
Sponsor class: OTHER
Collaborators: name: Therorna
First posted: 2024-01-16
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study is a randomized, double-blind, placebo controlled clinical exploratory study to evaluate the safety, tolerability and immunogenicity of TI-0010 vaccine in healthy adults aged 18-59. TI-0010 was manufactured by Therorna Inc. TI-0010 is a novel lipid nanoparticles (LNP) -encapsulated circRNA-based vaccine targeting RBD of SARS-CoV-2. Up to one hundred subjects will be enrolled into one of 4 cohorts. Low-dose(Dose Level 1) is for Cohort 1 and Cohort 2 , and the high dose (Dose Level 2) for Cohort 3 and Cohort 4. Cohort 1 and Cohort 3 receive 2 doses (with a 28 day interval) via intramuscular injection respectively, and Cohort 2 and Cohort 4 receive 1 dose via intramuscular injection respectively. Participants are randomized to receive TI-0010 or placebo in a 4:1 ratio.

Detailed description: This study is a randomized, double-blind, placebo controlled clinical exploratory study to evaluate the safety, tolerability and immunogenicity of TI-0010 vaccine in healthy adults aged 18-59. TI-0010 was manufactured by Therorna Inc. TI-0010 is a novel lipid nanoparticles (LNP) -encapsulated circRNA-based vaccine targeting RBD of SARS-CoV-2. Up to one hundred subjects will be enrolled into one of 4 cohorts. Low-dose(Dose Level 1) is for Cohort 1 and Cohort 2 , and the high dose(Dose Level 2) for Cohort 3 and Cohort 4. Cohort 1 and Cohort 3 receive 2 doses (with a 28 day interval) via intramuscular injection respectively, and Cohort 2 and Cohort 4 receive 1 dose via intramuscular injection respectively. Participants are randomized to receive TI-0010 or placebo in a 4:1 ratio. Follow-up visits will occur Days 3,7,14 and 28 post each vaccination, as well as 3, 6, 9 and 12 months for the single dose recipients after vaccination and for those who receive two doses post the second vaccination. The primary objective is to evaluate the safety and tolerability of the TI-0010 vaccine in adults within 28 days post each vaccination. The secondary objective is to evaluate the humoral and cellular immune responses of the TI-0010 vaccine in adults after a single dose or two doses of vaccination, to evaluate the safety of the TI-0010 vaccine within 1 year after vaccination in the adult population and to evaluate the immune persistence of TI-0010 vaccine after a single dose and two doses of administration.

Eligibility criteria: Inclusion Criteria:

* Understands and agrees to comply with the study procedures and provides written informed consent.
* Participant shall be in good general health within the age range of 18 to 59 years old when signing ICF, and can comply with study procedures
* For participant of childbearing potential: negative pregnancy test, adequate contraception or has abstained from all activities that could result in pregnancy after signing ICF, agreement to continue adequate contraception through 3 months following vaccine administration, and not currently breastfeeding.
* Participants have not received any SARS-CoV-2 vaccine before screening; Or if participants have previously received SARS-CoV-2 vaccination, who vaccinated at least 6 months from the last vaccination date.
* Participant has tested positive or had COVID-infection related symptoms at least 4 months prior to screening.

Exclusion Criteria:

* Arm 2/4 only: Individuals haven't completed full vaccination schedule with any approved or investigational COVID-19 vaccines.
* Individuals with clinically significant laboratory or ECG abnormalities at Screening.
* BMI \>30 kg/m2 or \<18 kg/m2
* Positive RT-PCR test for SARS-CoV-2 at the screening site
* Known exposure to someone with SARS-CoV-2 infection or COVID-19 in the past 5 days
* Postive test for HBsAg or HCV
* Participant is acutely ill 4 weeks prior to Day1, or feberile (body temperature no less than 37.3 Celcius 72 hours prior to or at Day 1
* Has received systemic immunosuppressants or immune-modifying drugs for \>14 days in total within 6 months prior to Screenin or is anticipating the need for immunosuppressive treatment at any time during participation in the study
* Participation in a study of investigational drug/device 30 days prior to Screening
* Individuals with a history of autoimmune disease or an active autoimmune disease requiring therapeutic intervention
* History of sever adverse reaction associated with a vaccine and/or severe allergic reaction to any component of the study intervention(s)
* Previous vaccination with any vaccine 28 days prior Screening
* Receipt of blood/plasma products or immunoglobulin 3 months prior Screening
* Other medical or psychiatric condition that may increase the risk of study participation or, in the investigator's judgment, make the individual inappropriate for the study

Primary outcomes:
measure: solicited adverse events (AEs)
timeFrame: Up to 14 days following each injection among all participants.
measure: The incidence of abnormal changes in laboratory indicators (including blood routine, blood biochemistry, thyroid function, coagulation function, and urine routine. )
timeFrame: Up to 3 days following each injection among all participants.
Secondary outcomes:
measure: Geometric mean titer(GMT) of SARS-CoV-2 neutralizing antibodies
timeFrame: Baseline, 7 days, 14 days, 28 days after Dose 1； 7 days, 14 days, 28 days after Dose 2（only for Cohort 1/3）； 3 months, 6 months, 9 months and 12 months
measure: Geometric mean titer fold increase(GMI) of SARS-CoV-2 neutralizing antibodies compared to baseline
timeFrame: Baseline, 7 days, 14 days, 28 days after Dose 1； 7 days, 14 days, 28 days after Dose 2（only for Cohort 1/3）； 3 months, 6 months, 9 months and 12 months
measure: Seroconversion rates(SCRs) of SARS-CoV-2 neutralizing antibodies
timeFrame: Baseline, 7 days, 14 days, 28 days after Dose 1； 7 days, 14 days, 28 days after Dose 2（only for Cohort 1/3）； 3 months, 6 months, 9 months and 12 months
measure: Geometric mean titer(GMT) of SARS-CoV-2 RBD-binding IgG
timeFrame: Baseline, 7 days, 14 days, 28 days after Dose 1； 7 days, 14 days, 28 days after Dose 2（only for Cohort 1/3）； 3 months, 6 months, 9 months and 12 months
measure: Geometric mean titer fold increase(GMI) of SARS-CoV-2 RBD-binding IgG compared to baseline
timeFrame: Baseline, 7 days, 14 days, 28 days after Dose 1； 7 days, 14 days, 28 days after Dose 2（only for Cohort 1/3）； 3 months, 6 months, 9 months and 12 months
measure: Seroconversion rates(SCRs) of SARS-CoV-2 RBD-binding IgG
timeFrame: Baseline, 7 days, 14 days, 28 days after Dose 1； 7 days, 14 days, 28 days after Dose 2（only for Cohort 1/3）； 3 months, 6 months, 9 months and 12 months
measure: The ratio of IL-2, IL-4, IFN- γ and TNF- α in T lymphocyte subsets (CD4+，CD8+) and memory T cell subsets (CD4+，CD8+).
timeFrame: Baseline, 7 days, 14 days, 28 days after Dose 1； 7 days, 14 days, 28 days after Dose 2（only for Cohort 1/3）； 3 months, 6 months, 9 months and 12 months
measure: Incidence of unsolicited Adverse Events (AEs)
timeFrame: From the time of first dose vaccination to day 28 after Dose 2 for Cohort 1/3; Up to day 28 after vaccination for Cohort 2/4.
measure: Incidence of Serious Adverse Events (SAEs), AE of Special Interest (AESIs), and Medically-attended Aes (MAAEs)
timeFrame: Day 0 to 12 months after Dose 2 for Cohort 1/3； Up to 12 months after vaccination for Cohort 2/4.
Other outcomes:
Locations:
city: Bengbu
country: China
facility: The Second Affiliated Hospital Of BengBu Medical College
state: Anhui
Study officials:
affiliation: The Second Affiliated Hospital of Bengbu Medical College
name: Xiaoli Li, Master
role: PRINCIPAL_INVESTIGATOR
References: