Official Title
A Phase 2/3, Randomized, Double-blinded , Parallel Controlled Trial to Evaluate the Immunogenicity, Safety and Efficacy of A Heterologous Booster Dose With COVID-19 mRNA Vaccines (Bivalent) , in Previously Vaccinated Subjects Against COVID-19 With 2/3 Doses COVID-19 Vaccine Compared to a Booster Dose With mRNA COVID-19 Vaccine(Pfizer Bivalent Vaccine)in Adults.
Brief Summary

Primary Immunogenicity Objective:Cohort 1: GMTs of SARS-CoV-2 Omicron and related strainneutralizing antibody levels for SWIM816.Cohort 2: To demonstrate the non- inferiority ofneutralizing antibody response in terms of geometric mean titers (GMT) of COVID-19 mRNAvaccine(SWIM816) compare with mRNA COVID-19 vaccine(Pfizer Bivalent vaccine) 14 days postdose.Primary Safety Objective:To assess the reactogenicity and safety of a booster dose in aheterologous vaccination regimen in subjects previously immunized with 2/3 doses ofCOVID-19 vaccine with or without previously diagnosed with COVID-19.Secondary Immunogenicity Objectives:To describe the neutralizing antibody response atD29, D91 and D181.To describe binding antibody profile at D01, D15, D29, D91 and D181 ofeach study group.Secondary Safety Objective:To assess the reactogenicity and safety of third or fourthbooster dose in a heterologous vaccination regimen in subjects previously immunized with2/3 COVID-19 vaccine doses.Exploratory Objective:1.Documented confirmed SARS-CoV-2 symptomaticinfection;2.Todemonstrate the cellular immune response profile at study group (30subjects per each group for cellular immune testing).

Detailed Description

Endpoints:

Cohorts 1: GMT of SARS-CoV-2 Omicron (such as BA.5, BQ.1,XBB) and reference strain
neutralizing antibody(Delta and other circulating strain) levels for SWIM816 on D15 after
study vaccination.

Cohorts 1: GMFR of SARS-CoV-2 Omicron (such as BA.5, BQ.1, XBB) and reference strain
neutralizing.

antibody (other circulating strain) levels for SWIM816 on D15 after study vaccination.

Cohorts 1: % of participants with seroresponse to SWIM816 for GMTs of SARS-CoV-2
Omicron(such as BA.5, BQ.1, XBB) and reference strain neutralizing antibody (other
circulating strain) levels on D15 after study vaccination.

Cohorts 2 (≥18 years ) Non-inferiority analysis: Geometric Mean Ratio (GMR) of SARS-CoV-2
Omicron (such as BA.5, BQ.1,XBB)-neutralizing antibody (other circulating strain) levels
for SWIM816 to Pfizer Bivalent vaccine on D15 after study vaccination.

Endpoints:

Occurrence of local and systemic AEs reported within 7 days after study vaccination.

Occurrence of unsolicited AEs reported within 28 days after vaccination. Frequency,
severity and relatedness of adverse events within 28 days after vaccination booster dose.

Endpoints:

Cohorts 1+2 : GMTs of Pseudovirus SARS-CoV-2 Omicron (such as BA.5, BQ.1,XBB) and
reference strain neutralizing antibody levels for SWIM816 before and on D29, D91, D181
after study vaccination.

Cohorts 1+2 : GMFR of SARS-CoV-2 Omicron (such as BA.5, BQ.1,XBB) and reference
strainneutralizingantibody levels for SWIM816 before and on D29, D91, D181 after study
vaccination.

Cohorts 1: % of participants with seroresponse to SWIM816 for GMTs of SARS-CoV-2
Omicron(such as BA.5, BQ.1, XBB) and reference strain neutralizing antibody (other
circulating strain) levels on D29, D91, D181 after study vaccination.

Cohorts 1 : GMTs and GMI of IgG profile at D01, D15, D29 , D91and D181 of each study
group.

Cohorts 1: GMTs of Pseudovirus SARS-CoV-2 Omicron (such as BA.5, BQ.1,XBB) and reference
strain neutralizing antibody levels for SWIM516 before and on D15, D29, D91, D181 after
study vaccination.

Cohorts 1: GMFR of SARS-CoV-2 Omicron (such as BA.5, BQ.1,XBB) and reference strain
neutralizing antibody levels for SW-BIC-213 before and on D15, D181 after study
vaccination.

Endpoints:

Serious AEs (SAEs), AEs leading to withdrawal and AEs of special interest (AESIs) within
180 days.

Endpoints:

Occurrence of confirmed symptomatic cases during the study period. Number of confirmed
SARS-CoV-2 symptomatic cases; Severity of confirmed cases of SARS-CoV-2 infection(WHO
scale). Number of IFN-γ positive (characterizing Th1) and IL-4 positive (characterizing
Th2) T cell subsets on D8 and Day 15 [ Time Frame: Day 8 and Day 15 after the study
vaccination .]

Not yet recruiting
Immunogenicity
Safety

Biological: Phase II:SWIM816;SARS-Cov-2;

The study will be performed in people who were previously vaccinated with 2/3 doses of
COVID-19 vaccine, with or without previously diagnosed with COVID-19. The interval
between the date of last dose and the date of this study vaccination should be 6 to 24
months.

There are 2 groups in phase 2 stage, total number 200 subjects who are ≥18 years old.
Details as below:

Group 1: (N=100) - SWIM816 25 μg; Group 2: (N=100) - SW-BIC-213 25 μg;

Biological: Phase II:SW-BIC-213;SARS-Cov-2;

The study will be performed in people who were previously vaccinated with 2/3 doses of
COVID-19 vaccine, with or without previously diagnosed with COVID-19. The interval
between the date of last dose and the date of this study vaccination should be 6 to 24
months.

There are 2 groups in phase 2 stage, total number 200 subjects who are ≥18 years old.
Details as below:

Group 1: (N=100) - SWIM816 25 μg; Group 2: (N=100) - SW-BIC-213 25 μg;

Biological: PhaseIII:SWIM816;SARS-Cov-2;

The study will be performed in people who were previously vaccinated with 2/3 doses of
COVID-19 vaccine, with or without previously diagnosed with COVID-19. The interval
between the date of last dose and the date of this study vaccination should be 6 to 24
months.

There are two groups in phase 3 stage., total number 600 subjects who are ≥18 years old.
Details as below:

Group 1: (N=300) - SWIM816 (≥18 years old ) Group 2: (N=300) -Pfizer Bivalent vaccine
(≥18 years old)

Biological: PhaseIII:Pfizer(Pfizer Bivalent vaccine);SARS-Cov-2;

The study will be performed in people who were previously vaccinated with 2/3 doses of
COVID-19 vaccine, with or without previously diagnosed with COVID-19. The interval
between the date of last dose and the date of this study vaccination should be 6 to 24
months.

There are two groups in phase 3 stage., total number 600 subjects who are ≥18 years old.
Details as below:

Group 1: (N=300) - SWIM816 (≥18 years old ) Group 2: (N=300) -Pfizer Bivalent vaccine
(≥18 years old)

Eligibility Criteria

Inclusion Criteria:

1. Male or female aged ≥18 years old when signing ICF.

2. Participants who were previously vaccinated with 2/3 doses of COVID-19 vaccine, with
or without previously diagnosed with COVID-19. The interval between the date of last
dose and the date of this study vaccination should be 6 to 24 months.

3. Those who have not been infected with the novel coronavirus or have been infected
for more than 3 months.

4. The participant and/or his legally acceptable representative can sign written ICF,
and can fully understand the trial procedure, the risk of participating in the
trial, and other interventions that can be selected if they do not participate in
the trial.

5. The participant and/or his legally acceptable representative have the ability to
read, understand, and fill in record cards.

6. Healthy participants or participants with pre-existing medical conditions who are in
stable condition. The "pre-existing medical conditions" include but not limited to
hypertension, diabetes, chronic cholecystitis and cholelithiasis, chronic gastritis
that meet the described criteria. A stable medical condition is defined as disease
not requiring significant change in therapy or no need for hospitalization as a
consequence of worsening disease state for at least 3 months prior to enrollment.

7. Fertile men and women of childbearing potential voluntarily agree to take effective
contraceptive measures from signing ICF to 6 months after the study vaccination; the
pregnancy test results of women of childbearing potential are negative on screening.

Exclusion Criteria:

1. Presence of fever within 3 days before the study vaccination;

2. A history of infection or disease related to severe acute respiratory syndrome
(SARS), Middle East respiratory syndrome (MERS), or other disease corresponding use
of immunosuppressants;

3. A history of allergic reactions to any vaccine or drug, such as allergy, urticaria,
severe skin eczema, dyspnea, laryngeal edema, and angioneurotic edema;

4. A medical or family history of seizure, epilepsy, encephalopathy and psychosis;

5. Immunocompromised patients suffering from immunodeficiency diseases, important organ
diseases, immune diseases (including Guillain-Barre Syndrome [GBS], systemic lupus
erythematosus, rheumatoid arthritis, asplenia or splenectomy caused by any
circumstances, and other immune diseases that may have an impact on immune response
in the investigator's opinion), etc.

6. Long-term use of immunosuppressant therapy or immunomodulatory drugs for ≥14 days
within the first six months prior to enrollment. Whereas short-term (≤14 days) use
of oral, inhaled and topical steroids are allowed;

7. Those who are tested positive for HIV in terms of serology.

8. Patients on antituberculosis therapy;

9. Presence of severe or uncontrollable cardiovascular diseases, or severe or
uncontrollable disorders related to endocrine system, blood and lymphatic system,
liver and kidney, respiratory system, metabolic and skeletal systems, or
malignancies (skin basal cell carcinoma and carcinoma in-situ of cervix are
exceptions and will not be excluded), such as severe heart failure, severe pulmonary
heart disease, unstable angina, liver failure, or uremia;

10. Contraindications for intramuscular injection or intravenous blood sampling,
including thrombocytopenia and other blood coagulation disorders;

11. Participants who received any immunoglobulin or blood products in the previous 3
months before enrollment, or plan to receive similar products during the study;

12. Participants who received other investigational drugs or vaccines within 1 month
before the study vaccination;

13. Participants who is at the acute state of disease, such as acute onset of chronic
heart f ailure, acute sore throat,hypertensive encephalopathy, acute pneumonia,
acute renal insufficiency, acute cholecystitis;

14. Participants vaccinated with influenza vaccine within 14 days or with other vaccines
within 28 days before the study vaccination;

15. Those who donated blood or had blood loss (≥450 mL) within 3 months before the
vaccination or plan to donate blood during the study period;

16. Those who are pregnant or breast-feeding or plan to be pregnant during the study
period;

17. Those who plan to donate ovum or sperms during the study period;

18. Those who cannot follow the trial procedures, or cannot cooperate to complete the
study due to planned relocation or long-term outing;

19. Those unsuitable for participating in the clinical trial as determined by the
investigator because of other abnormalities that are likely to confuse the study
results, or non-conformance with the maximal benefits of the participants.

Eligibility Gender
All
Eligibility Age
Minimum: 18 Years ~ Maximum: N/A
Locations

Not Provided

Contacts

yang li, doctor
+856 02095779465
yang.li@stemirna.com

bin luo, bachelor
+856 02095779465
bin.luo@stemirna.com

Mayfong Mayxay, doctor, Principal Investigator
National Ethics Committee for Health Research(NECHR)

Stemirna Therapeutics
NCT Number