ChulaCov19 Vaccine in Healthy Adults

Safety Issues Clinical Trial

Official title:

A Phase 1/2, Dose-finding Study to Evaluate Safety, Tolerability, and Immunogenicity of the ChulaCov19 Vaccine in Healthy Adults

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04566276
• Other study ID #: ChulaVac 001
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: May 3, 2021
• Est. completion date: December 6, 2022

Study information

• Verified date: February 2023
• Source: Chulalongkorn University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will be conducted in 2 phases. Phase 1 of this study will be a single-centre, open label, dose escalation first in human (FIH) study conducted in 2 groups of healthy participants. Group 1 will enrol adults aged 18-55 years (inclusive); Group 2 will enroll elderly adults (elderly) aged 56-75 years (inclusive).

Phase 2 of this study will be a single centre, the proposed design will be observer-blind, placebo-controlled study to assess the safety, reactogenicity, and immunogenicity of ChulaCov19 vaccine in healthy adults (18-75 years of age inclusive).

Description:

This study will be conducted as a combined phase 1/2 study in healthy participants.

The first phase of the study will evaluate the safety, tolerability, and reactogenicity of escalating doses (10 µg, 25 µg, and 50 µg) of the ChulaCov19 vaccine, administered intramuscularly (IM) according to a repeat vaccination schedule (given 21 days apart) in healthy adults aged 18-55 years and in elderly adults aged 56-75 years, up to Visit 10 (Day 50 ±3).

The second phase of the study will evaluate the safety, tolerability, and reactogenicity of escalating doses of the ChulaCov19 vaccine, administered intramuscularly (IM) according to a repeat vaccination schedule (given 21 days apart) in healthy adults aged 18--75 years, up to Visit 10 (Day 50 ±3). The study will also evaluate the immunogenicity measured as neutralising antibody titre (measured by Micro-viral neutralising test [MicroVNT]) following repeat vaccination of escalating doses of the ChulaCov19 vaccine, administered IM according to a repeat vaccination schedule (given 21 days apart) in healthy adults aged 18-75 years, at Visit 9 (Day 29 +3).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 192
• Est. completion date: December 6, 2022
• Est. primary completion date: October 1, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Participants who meet all the following criteria at Screening are eligible to participate in the study:

Inclusion criteria:

1. Participants must be able to communicate effectively with study personnel and considered reliable, willing, and cooperative in terms of compliance with the protocol requirements.

2. Participants must sign the written informed consent form prior to undertaking any protocol related procedures.

3. Participants must have a body mass index (BMI) at Screening, calculated as the body mass divided (in kilograms [kg]) by the square of the body height (in metres [m]) of 18.0-30.0 kg/m2, inclusive.

4. Participants must have haematology, clinical chemistry, coagulation (for all participants in Phase 1, and, only if applicable, for participants in Phase 2), and urinalysis test results that are not deviating from the normal reference range by age and gender to a clinically relevant extent at Screening.

5. Males must be surgically sterile (>30 days since vasectomy with no viable sperm), practice true abstinence or, if engaged in sexual relations with a female of child-bearing potential, the participants and their partner must use an acceptable, highly effective, double-barrier contraceptive method* from Screening and for a period of at least 60 days after the last dose of investigational vaccine.

6. Women of child-bearing potential must practice true abstinence or, if engaged in sexual relations with a male, they must agree to use highly effective (failure rate of < 1% per year when used consistently and correctly), double-barrier contraceptive measures* throughout the study and intend to continue use of contraception for at least 60 days following the last vaccination.

• The PI is to assess the adequacy of methods of contraception on a case-by-case basis. These criteria do not apply if the participants are in a same-sex relationship.

7. Women of child-bearing potential must have a negative serum pregnancy test (beta human chorionic gonadotropin [ß-HCG]) at Screening and a negative urine-based test within 24 hours prior to each investigational vaccine administration.

8. Women of non-child-bearing potential must:

1. be classified as being postmenopausal (defined as having a history of amenorrhea of at least one year), or

2. where history of amenorrhea is less than one year, female participants must have a follicle stimulating hormone (FSH) level > 40 milli-international units per milliliter (mIU/mL), or

3. have a documented status of being surgically sterile (hysterectomy, bilateral oophorectomy, or tubal ligation/salpingectomy).

9. Participants must be in general good health based on medical history and physical examination, as determined by the PI, at Screening.

10. Body temperature must be less than 37.8ºC, at Screening.

11. Pulse must be no greater than 100 beats per minute, at Screening.

12. Systolic blood pressure (SBP) must be between 85 to 150 millimetres of mercury (mm Hg), inclusive, at Screening.

13. Participants must agree to refrain from donating blood, plasma, ovules, sperm, or organs during the whole study.

Adult Participants (Group 1 of Phase 1) only

14. Must be a male or female aged 18-55 years (inclusive) at the time of enrolment.

Elderly Participants (Group 2 of Phase 1) only

15. Must be a male or female aged 56-75 years (inclusive) at the time of enrolment.

Participants for Phase 2 only

16. Must be a male or female aged 18 -59 years (inclusive) at the time of enrolment.

Exclusion Criteria

The presence of any of the following criteria will constitute cause for the exclusion of the participant:

1. Presence of clinically significant medical history, unstable chronic or acute disease, or physical, or laboratory findings that, in the opinion of the PI may potentially increase the expected risk of exposure to the investigational vaccine, compromise the safety of the participant, or interfere with any aspect of study conduct or interpretation of results. This will include asthma and any thrombocytopenia or bleeding disorder contraindicating IM vaccination.

2. Presence of self-reported or medically documented significant medical or psychiatric condition(s).

3. Presence of an acute illness, as determined by the participating site PI or appropriate sub-PI, with or without fever (temperature = 38.0 ºC) within 72 hours prior to each vaccination.

4. Presence of birthmarks, tattoos, wound, or other skin conditions over the deltoid region of both arms that, in the PI's opinion, could reasonably obscure and interfere with evaluation of local ISRs.

5. Inadequate venous access to allow collection of blood samples.

6. Breastfeeding or planning to breastfeed from the time of the first vaccination through 60 days after the last vaccination, or pregnant as confirmed by a positive serum ß-HCG pregnancy test at Screening or positive urine pregnancy test at subsequent clinic visits at timepoints as delineated in the schedule of assessments.

7. Received any prophylactic or therapeutic vaccine, or licensed or unlicensed vaccine, drug, biologic, device, blood product, or medication, within 4 weeks of first vaccination or 5 half-lives (whichever is longer), or anticipate to do so in the follow-up period defined for this study.

8. Participant has previously participated in an investigational study involving LNPs (a component of the investigational vaccine assessed in this trial).

9. History of severe allergy (requiring hospital care), severe reaction to any drug or prior vaccination, or any known or suspected allergies or sensitivities to any component of the investigational vaccine or placebo.

10. History of ever had an anaphylaxis reaction to food, medication or vaccination.

11. Participant is immunosuppressed as caused by disease (such as HIV).

12. Chronic use (more than 14 continuous days) of or anticipated need to use, within the next 6 months, of any medications that may be associated with impaired immune responsiveness or with immunosuppression.

13. History of hepatitis B or hepatitis C infection.

14. Receipt of immunoglobulins or blood products within 3 months of first vaccination.

15. Requirement for antipyretic or analgesic medication on a daily or every other day basis from enrolment through 72 hours after vaccination.

16. Current use of any prescription or over-the-counter medications within 7 days prior to vaccination, unless approved by the PI.

17. History of alcohol or drug abuse that in the opinion of the PI could affect the participant's safety or compliance with study.

18. Participant unwilling to abstain from blood donation during the course of the study, and/or participation in any research study involving blood sampling (more than 450 mL /unit of blood), or blood donation to any blood bank during the 2 months prior to the Screening visit.

19. Close contact with anyone known to have SARS-CoV-2 infection within 30 days prior to vaccine administration.

20. Positive for SAR-CoV-2 by antibody IgG/IgM and anti spike IgG at screening

21. History of COVID-19 diagnosis (the criteria for COVID-19 diagnosis will follow the local guidelines).

22. On current treatment with investigational agents for prophylaxis of COVID-19.

23. Planning to travel outside Thailand from enrolment through 28 days after the second vaccination.

24. Residing in a nursing home or other skilled nursing facility or having a requirement for skilled nursing care.

25. Is a participant at high risk of SARS-CoV2 exposure in the opinion of the PI (e.g., healthcare workers, active health care workers with direct patient contact, emergency response personnel).

Elderly Participants (Group 2 of Phase 1) only

26. Chronically smoking (defined as =10 Pack years [packs/day × years smoked]) within the 12 months prior to enrolment.

27. Presence of co-morbidities that can be associated with an increased risk of severe COVID-19 Cancer, Chronic kidney diseases, COPD, cardiovascular disease, solid organ transplantation, DM type 2, HT, cerebrovascular disease, Obesity (BMI> 30 kg/m2)

Participants for Phase 2 only

28. Presence of co-morbidities that can be associated with an increased risk of severe COVID-19 Cancer, Chronic kidney diseases, COPD, cardiovascular disease, solid organ transplantation, DM type 2, uncontrolled HT, cerebrovascular disease

Related Conditions & MeSH terms

• COVID-19 Vaccine
• Safety Issues

Intervention

Biological:
• ChulaCov19 vaccine
SARS-Cov2 Wild-type S-spike mRNA/ lipid nanoparticle (LNP) vaccine

Other:
• Placebo
Saline

Locations

Country	Name	City	State
Thailand	Center of Excellence for Vaccine Trial (Vaccine Trial Centre), Faculty of Tropical Medicine Mahidol University	Bangkok
Thailand	Chula Vaccine Research Center (ChulaCRC) Faculty of Medicine Chulalongkorn University	Bangkok

Sponsors (7)

Lead Sponsor

Collaborator

Chulalongkorn University

Center of Excellence for Vaccine Trial (Vaccine Trial Centre), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand, Center of Excellence in Vaccine Research and Development, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, Chula Clinical Research Center (Chula CRC), King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, Chula Vaccine Research Center (ChulaVRC), Bangkok, Thailand, King Chulalongkorn Memorial Hospital (KCMH), Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, National Vaccine Institute, Thailand

Country where clinical trial is conducted

Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1 and 2: Frequency of Adverse Events	Frequency of Adverse Events	up to Day 50
Primary	Phase 1 and 2: Grade of Adverse Events	Grade of Adverse Events	up to Day 50
Primary	Phase 1 and 2: Frequency of solicited reportable local Adverse Events	Frequency of solicited reportable local Adverse Events (i.e., pain, tenderness, erythema/redness, induration/swelling, ulceration, scabs, ecchymosis, oedema, itching, paraesthesia, and hypersensitivity)	during a 7-day follow-up period post each vaccination
Primary	Phase 1 and 2: Grade of solicited reportable local Adverse Events	Grade of solicited reportable local Adverse Events: (i.e., pain, tenderness, erythema/redness, induration/swelling, ulceration, scabs, ecchymosis, oedema, itching, paraesthesia, and hypersensitivity)	during a 7-day follow-up period post each vaccination
Primary	Phase 1 and 2: Frequency of solicited reportable systemic reactogenicity Adverse Events	Frequency of solicited reportable systemic Adverse Events: (i.e., headache, fatigue, myalgia, malaise, fever, rigors, arthralgia, nausea/vomiting, diarrhea, light headedness, dizziness, or any other symptoms)	during a 7-day follow-up period post each vaccination
Primary	Phase 1 and 2: Grade of of solicited reportable systemic Adverse Events	Grade of solicited reportable systemic Adverse Events: (i.e., headache, fatigue, myalgia, malaise, fever, rigors, arthralgia, nausea/vomiting, diarrhea, light headedness, dizziness, or any other symptoms)	during a 7-day follow-up period post each vaccination
Primary	Phase 1 and 2: Frequency of Serious Adverse Events	Frequency of Serious Adverse Events	up to Day 387
Primary	Phase 1 and 2: Frequency of Medically-Attended Adverse Events	Frequency of Medically-Attended Adverse Events	up to Day 387
Primary	Phase 1 and 2: Frequency of New-Onset Chronic Medical Conditions	Frequency of New-Onset Chronic Medical Conditions	up to Day 387
Primary	Phase 1 and 2: Changes in vital signs	Changes in vital signs: (i.e., body temperature, respiratory rate, pulse rate, systolic blood pressure (SBP), and diastolic blood pressure (DBP))	up to Day 50
Primary	Phase 1 and 2: Changes in physical examinations	Changes in physical examinations: (i.e., head, ears, nose, throat, lungs, lymph nodes, heart, abdomen and skin)	up to Day 50
Primary	Phase 1 and 2: Changes in laboratory measurements	Changes in laboratory measurements: (i.e., haemoglobin (Hb), haematocrit (HCT), white blood cells (WBC), neutrophil, lymphocytes, eosinophil, basophil, monocytes, platelet, sodium, potassium, chloride, bicarbonate, blood urea nitrogen (BUN), creatinine, total protein, albumin, lipase, phosphorus, gamma-glutamyl transferase (GGT), glucose, creatinine phosphokinase (CPK), calcium, uric acid, C-reactive protein (CRP), alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), total bilirubin, estimated glomerular filtration rate (eGFR), prothrombin time (PR), partial thromboplastin time (PTT) and international normalized ratio (INR))	up to Day 50
Primary	Phase 1 and 2: Presence of injection site reactions	Presence of injection site reactions	up to Day 50
Primary	Phase 2: Geometric mean titers (GMT) in SARS-CoV-2-specific serum neutralising antibody levels	Geometric mean titers (GMT) in SARS-CoV-2-specific serum neutralising antibody levels	at Day 29 (7 days after the second dose)
Secondary	Phase 1: Geometric mean titers (GMT) in SARS-CoV-2-specific serum neutralising antibody levels	Geometric mean titers (GMT) in SARS-CoV-2-specific serum neutralising antibody levels	at Day 29 (7 days after the second dose)
Secondary	Phase 1 and Phase 2: Proportion of participants who achieved a greater than or equal to 4-fold rise from before vaccination in SARS-CoV-2-specific serum neutralising antibody levels	Proportion of participants who achieved a greater than or equal to 4-fold rise from before vaccination in SARS-CoV-2-specific serum neutralising antibody levels	At Day 29
Secondary	Phase 1 and Phase 2: Geometric mean fold rises (GMFR) in SARS-CoV-2-specific serum neutralising titers	Geometric mean fold rises (GMFR) in SARS-CoV-2-specific serum neutralising titers	from baseline to Day 29
Secondary	Phase 1 and Phase 2: Geometric mean titers (GMT) in SARS-CoV-2 surrogate viral neutralising antibody levels	Geometric mean titers (GMT) in SARS-CoV-2 surrogate viral neutralising antibody levels	at Day 29
Secondary	Phase 1 and Phase 2: Proportion of participants who achieved a greater than or equal to 4-fold rise from before vaccination in SARS-CoV-2 surrogate viral neutralising antibody levels	Proportion of participants who achieved a greater than or equal to 4-fold rise from before vaccination in SARS-CoV-2 surrogate viral neutralising antibody levels	at Day 29
Secondary	Phase 1 and Phase 2: Geometric mean fold rises (GMFR) in SARS-CoV-2 surrogate viral neutralising antibody titers	Geometric mean fold rises (GMFR) in SARS-CoV-2 surrogate viral neutralising antibody titers	from baseline to Day 29
Secondary	Phase 1 and Phase 2: Geometric mean titers (GMT) of SARS-Cov2-spike protein-binding IgG antibody	Geometric mean titers (GMT) of SARS-Cov2-spike protein-binding IgG antibody	at Day 29
Secondary	Phase 1 and Phase 2: Proportion of participants who seroconverted: achieving a greater than or equal to 4-fold rise in SARS-Cov2-spike protein-binding IgG antibody	Proportion of participants who seroconverted: achieving a greater than or equal to 4-fold rise in SARS-Cov2-spike protein-binding IgG antibody	from baseline to Day 29
Secondary	Phase 1 and Phase 2: Geometric mean fold rises (GMFR) in SARS-Cov2-spike protein-binding IgG antibody	Geometric mean fold rises (GMFR) in SARS-Cov2-spike protein-binding IgG antibody	from baseline to Day 29
Secondary	Phase 1 and Phase 2: Percentage of participants who have positive specific CD4 T-cell IFN? ELISpot responses	Percentage of participants who have positive specific CD4 T-cell IFN? ELISpot responses	Day 29
Secondary	Phase 1 and Phase 2: Percentage of participants who have positive specific CD8 T-cell IFN? ELISpot responses	Percentage of participants who have positive specific CD8 T-cell IFN? ELISpot responses	Day 29
Secondary	Phase 1 and Phase 2: Median number of spot-forming cells (SFC) per 1 million PBMCs	Median number of spot-forming cells (SFC) per 1 million PBMCs	Day 29
Secondary	Phase 1 and Phase 2: Percentage of participants who shows positive specific Th1 responses	Percentage of participants who shows positive specific Th1 responses	Day 29
Secondary	Phase 1 and Phase 2: Percentage of participants who shows positive specific Th2 responses	Percentage of participants who shows positive specific Th2 responses	Day 29
Secondary	Phase 1 and Phase 2: Median percentage specific Th1 responses	Median percentage specific Th1 responses	Day 29
Secondary	Phase 1 and Phase 2: Median percentage specific Th2 responses	Median percentage specific Th2 responses	Day 29