ChulaCov19 Vaccine in Healthy Adults

NCT04566276 | Completed Phase 1 DMC

• 1 other identifier: ChulaVac 001
• Study Type: interventional
• Target: 192
• Locations: 1 country
• Sites: 2

Brief 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).

Conditions

COVID-19 Vaccine; Safety Issues

Keywords

tolerability; reactivity; immunogenicity; healthy adults; healthy elderlies; coronavirus disease 2019; SARS-CoV-2-specific serum neutralising antibody titer; SARS-CoV-2-surrogate viral neutralising antibody; SARS-Cov2 spike protein-binding IgG antibody titer; SARS-Cov2 spike protein-specific CD4+ and CD8+ T-cells responses; IFNγ enzyme-linked immune absorbent spot (ELISpot); SARS-Cov2 spike protein-specific Th1/Th2 polarisation; novel lipid nanoparticles (LNPs)-encapsulated mRNA-based vaccine

Outcome Measures

Primary Outcomes (14)

• Phase 1 and 2: Frequency of Adverse Events

  Frequency of Adverse Events

  up to Day 50

• Phase 1 and 2: Grade of Adverse Events

  Grade of Adverse Events

  up to Day 50

• 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

• 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

• 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

• 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

• Phase 1 and 2: Frequency of Serious Adverse Events

  Frequency of Serious Adverse Events

  up to Day 387

• Phase 1 and 2: Frequency of Medically-Attended Adverse Events

  Frequency of Medically-Attended Adverse Events

  up to Day 387

• Phase 1 and 2: Frequency of New-Onset Chronic Medical Conditions

  Frequency of New-Onset Chronic Medical Conditions

  up to Day 387

• 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

• 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

• 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

• Phase 1 and 2: Presence of injection site reactions

  Presence of injection site reactions

  up to Day 50

• 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 Outcomes (16)

• Phase 1: Geometric mean titers (GMT) in SARS-CoV-2-specific serum neutralising antibody levels

  at Day 29 (7 days after the second dose)

• 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

  At Day 29

• Phase 1 and Phase 2: Geometric mean fold rises (GMFR) in SARS-CoV-2-specific serum neutralising titers

  from baseline to Day 29

• Phase 1 and Phase 2: Geometric mean titers (GMT) in SARS-CoV-2 surrogate viral neutralising antibody levels

  at Day 29

• 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

  at Day 29

Study Arms (8)

Adult Cohort 1: 10 µg

EXPERIMENTAL

12 healthy adults aged 18-55 years will receive 10 µg of the vaccine IM

Biological: ChulaCov19 vaccine

Adult Cohort 2: 25 µg

EXPERIMENTAL

12 healthy adults aged 18-55 years will receive 25 µg of the vaccine IM

Biological: ChulaCov19 vaccine

Adult Cohort 3: 50 µg

EXPERIMENTAL

12 healthy adults aged 18-55 years will receive 50 µg of the vaccine IM

Biological: ChulaCov19 vaccine

Elderly Cohort 1 :10 µg

EXPERIMENTAL

12 elderlies aged 56-75 years will receive 10 µg of the vaccine IM

Biological: ChulaCov19 vaccine

Elderly Cohort 2: 25 µg

EXPERIMENTAL

12 elderlies aged 56-75 years will receive 25 µg of the vaccine IM

Biological: ChulaCov19 vaccine

Elderly Cohort 3: 50 µg

EXPERIMENTAL

12 elderlies aged 56-75 years will receive 50 µg of the vaccine IM

Biological: ChulaCov19 vaccine

Phase 2: ChulaCov19 vaccine Dose 50 ug

EXPERIMENTAL

adults between 18 and 59 years of age will receive 2 IM ChulaCov19 vaccine Dose 50 ug vaccinations; administered 21days apart (on Day 1 and Day 22 ±3)

Biological: ChulaCov19 vaccine

Phase 2: Placebo

OTHER

adults between 18 and 59 years of age will receive 2 IM saline vaccinations; administered 21days apart (on Day 1 and Day 22 ±3)

Other: Placebo

Interventions

ChulaCov19 vaccine BIOLOGICAL

SARS-Cov2 Wild-type S-spike mRNA/ lipid nanoparticle (LNP) vaccine

Adult Cohort 1: 10 µg; Adult Cohort 2: 25 µg; Adult Cohort 3: 50 µg; Elderly Cohort 1 :10 µg; Elderly Cohort 2: 25 µg; Elderly Cohort 3: 50 µg; Phase 2: ChulaCov19 vaccine Dose 50 ug

Placebo OTHER

Saline

Phase 2: Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must be able to communicate effectively with study personnel and considered reliable, willing, and cooperative in terms of compliance with the protocol requirements.
• Participants must sign the written informed consent form prior to undertaking any protocol related procedures.
• 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.
• 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.
• 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.
• 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.
• Women of child-bearing potential must have a negative serum pregnancy test (beta human chorionic gonadotropin \[β-HCG\]) at Screening and a negative urine-based test within 24 hours prior to each investigational vaccine administration.
• Women of non-child-bearing potential must:
• be classified as being postmenopausal (defined as having a history of amenorrhea of at least one year), or
• 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
• have a documented status of being surgically sterile (hysterectomy, bilateral oophorectomy, or tubal ligation/salpingectomy).
• Participants must be in general good health based on medical history and physical examination, as determined by the PI, at Screening.
• Body temperature must be less than 37.8ºC, at Screening.
• Pulse must be no greater than 100 beats per minute, at Screening.

You may not qualify if:

• 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.
• Presence of self-reported or medically documented significant medical or psychiatric condition(s).
• 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.
• 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.
• Inadequate venous access to allow collection of blood samples.
• 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 β-HCG pregnancy test at Screening or positive urine pregnancy test at subsequent clinic visits at timepoints as delineated in the schedule of assessments.
• 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.
• Participant has previously participated in an investigational study involving LNPs (a component of the investigational vaccine assessed in this trial).
• 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.
• History of ever had an anaphylaxis reaction to food, medication or vaccination.
• Participant is immunosuppressed as caused by disease (such as HIV).
• 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.
• History of hepatitis B or hepatitis C infection.
• Receipt of immunoglobulins or blood products within 3 months of first vaccination.
• Requirement for antipyretic or analgesic medication on a daily or every other day basis from enrolment through 72 hours after vaccination.

Sponsors & Collaborators

• Chulalongkorn University: lead
• Chula Vaccine Research Center (ChulaVRC), Bangkok, Thailand: collaborator
• Center of Excellence in Vaccine Research and Development, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand: collaborator
• Chula Clinical Research Center (Chula CRC), King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand: collaborator
• King Chulalongkorn Memorial Hospital (KCMH), Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand: collaborator
• Mahidol University: collaborator
• National Vaccine Institute, Thailand: collaborator

Study Sites (2)

Chula Vaccine Research Center (ChulaCRC) Faculty of Medicine Chulalongkorn University

Bangkok, 10330, Thailand

Location

Center of Excellence for Vaccine Trial (Vaccine Trial Centre), Faculty of Tropical Medicine Mahidol University

Bangkok, Thailand

Location

Related Publications (1)

• Puthanakit T, Prompetchara E, Gatechompol S, Ketloy C, Thitithanyanont A, Jongkaewwattana A, Buranapraditkun S, Ubolyam S, Kerr SJ, Sophonphan J, Apornpong T, Kittanamongkolchai W, Siwamogsatham S, Sriplienchan S, Patarakul K, Theerawit T, Promsena P, Nantanee R, Manomaisantiphap S, Chokyakorn S, Hong L, Samija M, Montefiori DC, Gao H, Eaton A, Wijagkanalan W, Alameh MG, Weissman D, Ruxrungtham K; ChulaVac001-Phase 2 study team. Phase II prefusion non-stabilised Covid-19 mRNA vaccine randomised study. Sci Rep. 2024 Jan 29;14(1):2373. doi: 10.1038/s41598-023-49653-6.

  PMID: 38287068 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

ChulaCov19 vaccine

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

• Kiat Ruxrungtham, MD

  Center of Excellence in Vaccine Research and Development, Faculty of Medicine, Chulalongkorn University

  STUDY DIRECTOR

Study Design

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

Model Details: Phase 1: Group 1 (healthy adults aged 18 to 55 years) and Group 2 (elderlies aged 56 to 75 years) will be enrolled sequentially in an ascending dose fashion (10 µg, 25 µg, 50 µg). Up to 36 eligible healthy volunteers for each of the 2 age groups will be enrolled into 1 of 3 treatment cohorts (12 participants/ cohort). For each cohort, if only 1 participant withdraws prior to the second vaccination, no replacement is deemed necessary. For each cohort, if more than 1 participant withdraws prior to the second vaccination all withdrawn participants will be replaced. Phase 2: The Phase 2 adult cohorts will include adults between 18 and 59 years of age (inclusive). Participants in the Phase 2 will be enrolled into at least 1 dose level cohort with a vaccination dose of 50 ug which was determined by DSMB and SRPT review and approval of the applicable Phase 1 data. Phase 2 treatment group will consist of participants randomly assigned to active treatment versus placebo in a ratio of 4:1.

Study Record Dates

• First Submitted: September 15, 2020
• First Posted: September 28, 2020
• Study Start: May 3, 2021
• Primary Completion: October 1, 2022
• Study Completion: December 6, 2022
• Last Updated: February 9, 2023

Record last verified: 2023-02

Locations

TH (2)