A Study on the Safety, Tolerability and Immune Response of SARS-CoV-2 Sclamp (COVID-19) Vaccine in Healthy Adults

NCT04495933 | Completed Phase 1

• 2 other identifiers: UQ-1-SARS-CoV-2-SclampACTRN12620000674932p
• Study Type: interventional
• Target: 216
• Locations: 1 country
• Sites: 1

Brief Summary

This study is being conducted to look at the safety and immune response (how the immune system of the human body reacts) to a vaccine for SARS-CoV-2 (the virus responsible for COVID-19 infection) when administered as an intramuscular injection (an injection directly into the muscle) to the upper arm of healthy participants, on two occasions at least 28 days apart.

Conditions

SARS-CoV2; Covid19

Keywords

SARS-CoV-2 infection

Outcome Measures

Primary Outcomes (8)

• Frequency of Solicited local reactogenicity adverse events (AEs)

  \- the frequency of solicited local reactogenicity adverse events (AEs)

  7 days following each vaccination (at Days 1 and 29)

• Frequency of Solicited systemic reactogenicity adverse events (AEs)

  \- the frequency of solicited systemic reactogenicity AEs

  7 days following each vaccination (at Days 1 and 29)

• Grading of Solicited local reactogenicity adverse events (AEs)

  \- the grading of solicited local reactogenicity adverse events (AEs)

  7 days following each vaccination (at Days 1 and 29)

• Grading of Solicited systemic reactogenicity adverse events (AEs)

  \- the grading of solicited systemic reactogenicity AEs

  7 days following each vaccination (at Days 1 and 29)

• Unsolicited adverse events (AEs)

  \- the frequency, duration, intensity and relationship to vaccination of unsolicited local adverse events (AEs)

  28 days following each vaccination (at Days 1 and 29)

• Serious adverse events (SAEs), Medically attended adverse events (MAAEs) and any Adverse events (AEs) leading to study withdrawal at any time during the study

  \- the frequency, duration, intensity and relationship to vaccination of Serious adverse events (SAEs), Medically attended adverse events (MAAEs) and any Adverse events (AEs) leading to study withdrawal at any time during the study (including decision by the Principal Investigator \[PI\] not to proceed with the second dose) at any time during the study

  through study completion (394 days)

• Geometric Mean Titer (GMT) of the serum antibody response

  \- Geometric mean titre (GMT) of the serum antibody response compared to placebo

  28 days following each vaccination (Days 29 and 57)

• Geometric Mean Titer (GMT) of the serum neutralizing antibody (NAb) response to SARS-CoV-2 virus

  GMT of the serum NAb titres to SARS-CoV-2 virus compared to placebo

  28 days following each vaccination (Days 29 and 57)

Secondary Outcomes (3)

• Total serum antibody immune responses

  through study completion (394 days)

• proportion of participants with ≥ 4 fold increase in titer above baseline

  through study completion (394 days)

• GMT of the serum neutralizing antibody (NAb) titres

  through study completion (394 days)

Study Arms (3)

MF59 adjuvanted SARS-CoV-2 Sclamp vaccine 5mcg

EXPERIMENTAL

SARS-CoV-2 Sclamp antigen 5 mcg mixed with MF59 adjuvant in 0.5 mL suspension, administered in a two dose regimen, at least 28 days apart.(Cohorts 1 \& 4)

Biological: MF59 adjuvanted SARS-CoV-2 Sclamp vaccine 5mcg; Other: Placebo

MF59 adjuvanted SARS-CoV-2 Sclamp vaccine 15mcg

EXPERIMENTAL

SARS-CoV-2 Sclamp antigen 15 mcg mixed with MF59 adjuvant in 0.5 mL suspension, administered in a two dose regimen, at least 28 days apart. (Cohorts 2 \& 5)

Biological: MF59 adjuvanted SARS-CoV-2 Sclamp vaccine 15mcg; Other: Placebo

MF59 adjuvanted SARS-CoV-2 Sclamp vaccine 45mcg

EXPERIMENTAL

SARS-CoV-2 Sclamp antigen 45 mcg mixed with MF59 adjuvant in 0.5 mL suspension, administered in a two dose regimen, at least 28 days apart. (Cohorts 3 \& 6)

Biological: MF59 adjuvanted SARS-CoV-2 Sclamp vaccine 45mcg; Other: Placebo

Interventions

MF59 adjuvanted SARS-CoV-2 Sclamp vaccine 5mcg BIOLOGICAL

MF59 adjuvanted SARS-CoV-2 Sclamp vaccine 5mcg

MF59 adjuvanted SARS-CoV-2 Sclamp vaccine 5mcg

MF59 adjuvanted SARS-CoV-2 Sclamp vaccine 15mcg BIOLOGICAL

MF59 adjuvanted SARS-CoV-2 Sclamp vaccine 15mcg

MF59 adjuvanted SARS-CoV-2 Sclamp vaccine 15mcg

MF59 adjuvanted SARS-CoV-2 Sclamp vaccine 45mcg BIOLOGICAL

MF59 adjuvanted SARS-CoV-2 Sclamp vaccine 45mcg

MF59 adjuvanted SARS-CoV-2 Sclamp vaccine 45mcg

Placebo OTHER

sterile saline

MF59 adjuvanted SARS-CoV-2 Sclamp vaccine 15mcg; MF59 adjuvanted SARS-CoV-2 Sclamp vaccine 45mcg; MF59 adjuvanted SARS-CoV-2 Sclamp vaccine 5mcg

Eligibility Criteria

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

You may qualify if:

• Healthy male or non-pregnant female, ≥18 and ≤55 years of age, with BMI \>18 and \<34.0 kg/m2 and body weight ≥50.0 kg for males and ≥45.0 kg for females (Part 1); Healthy male or non-pregnant female, ≥56 years of age, with BMI \>18 and \<34.0 kg/m2 and body weight ≥50.0 kg for males and ≥45.0 kg for females (Part 2)
• Healthy as defined by:
• The absence of clinically significant history of neurological, endocrine, cardiovascular, respiratory, haematological, immunological, psychiatric, gastrointestinal, renal, hepatic, and metabolic disease (Part 1); b. The absence of clinically significant history of a pre-existing medical condition that is not stable (neurological, endocrine, cardiovascular, respiratory, haematological, immunological, psychiatric, gastrointestinal, renal, hepatic, and metabolic disease). A stable medical condition is defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 3 months before enrolment (Part 2)
• Non-smokers or social smokers (defined as the equivalent of fewer than 10 cigarettes per week). Ex-heavy smokers (heavy smoking defined as the equivalent of 25 or more cigarettes per day) may be admitted if they have quit, or reduced their cigarette intake to the defined level of social smoking, for a period of at least 12 months.
• Women of childbearing potential (WOCBP) or men whose sexual partners are WOCBP must be able and willing to use at least 2 highly effective methods of contraception commencing at enrolment, during the study and for 3 months after last treatment administration. A female subject is considered to be a WOCBP following menarche and until she is in a postmenopausal state for 12 consecutive months (without an alternative medical cause) or otherwise permanently sterile (for which acceptable methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy). A follicle-stimulating hormone (FSH) test may be used to confirm post-menopausal state. Examples of acceptable methods of contraceptive methods (for female subjects) to be used throughout the study include:
• Simultaneous use of hormonal contraceptives, started at least 28 days prior to first study treatment administration and must agree to use the same hormonal contraceptive throughout the study, and condom for the male partner;
• Simultaneous use of intra-uterine contraceptive device, placed at least 28 days prior to first study treatment administration, and condom for the male partner;
• Simultaneous use of diaphragm or cervical cap and male condom for the male partner, started at least 28 days prior to first study treatment administration;
• Sterile male partner (vasectomized since at least 6 months prior to first study treatment administration);
• True abstinence, defined as no sexual intercourse with a male partner, (for heterosexual couples) for at least 28 days prior to first study treatment administration and for at least the duration of the study. Periodic abstinence and withdrawal are not acceptable methods.
• WOCBP must have a negative urine pregnancy test prior to receiving each dose.
• Male subjects (including men who have had a vasectomy) with a pregnant partner, a female partner not of childbearing potential, or a same sex partner, must agree to use a condom from the first study treatment administration until at least 90 days after the last study treatment administration.
• Male subjects must be willing not to donate sperm until 90 days following the last study treatment administration.
• Must be able to attend all visits for the duration of the study and to comply with all study procedures according to the study schedule.
• Capable of, and have given, written informed consent.

You may not qualify if:

• Any clinically significant abnormality or vital sign abnormality at physical examination (including baseline high blood pressure \[140/90\] after 3 repeated measurements or high random blood sugar \[non-fasting\]), clinically significant abnormal laboratory test results or positive test for HIV, hepatitis B, or hepatitis C found during medical screening (Part 1); Any clinically significant abnormality or vital sign abnormality at physical examination, or uncontrolled hypertension in adults aged ≥ 56 years and older ,or high random blood sugar \[non-fasting\]), clinically significant abnormal laboratory test results or positive test for HIV, hepatitis B, or hepatitis C found during medical screening (Part 2).
• Any acute or chronic ongoing illness which, in the judgement of the investigator, may preclude the subject's participation.
• Any subject that has an active COVID-19 infection (positive COVID-19 test: nasal/oropharyngeal swab and/or positive serum antibody response) at screening, or Day 1, or has been in close contact with someone who has an active COVID-19 infection, or has recovered from a previous COVID-19, SARS-CoV-1, or MERS infection.
• Positive pregnancy, urine drug screen, or alcohol breath test at screening.
• Known history of allergic reactions or hypersensitivity to vaccines, or to any excipient in the formulation (including the adjuvant, MF59C.1).
• Presence of a known, or suspected, impairment of the immune system including, but not limited to, HIV, autoimmune disorders, immunosuppressant therapy, and diabetes mellitus.
• History of a known, or suspected, respiratory system disorder including, but not limited to, cystic fibrosis, reactive airway disease, emphysema, chronic bronchitis, chronic obstructive pulmonary disease (COPD), or asthma, excluding childhood asthma (Part 1); History of a known, or suspected, or currently unstable medical condition that may expose the participant to an increased risk for severe SARS-CoV-2 disease, such as a respiratory system disorder including, but not limited to, cystic fibrosis, reactive airway disease, emphysema, chronic bronchitis, chronic obstructive pulmonary disease (COPD), or asthma, excluding childhood asthma, uncontrolled hypertension, ischemic or structural heart disease, chronic kidney disease, chronic liver disease, endocrine disorder and neurological illness (Part 2).
• History of significant alcohol abuse within 12 months prior to screening.
• Positive test for drugs of abuse (such as marijuana/tetrahydrocannabinol \[THC\] products, amphetamine, methamphetamine, methadone, barbiturates, benzodiazepines, cocaine, opiates, methylenedioxymethamphetamine \[MDMA\], or phencyclidine \[PCP\]) at screening, prior to dosing, or a history of drug abuse within 12 months prior to screening.
• Participation in a clinical research study involving the administration of an investigational, or marketed, drug or device within 30 days prior to receiving the first treatment administration, or administration of a biological product in the context of a clinical research study within 90 days prior to the first dosing, or concomitant participation in an investigational study involving no drug, vaccine, or device administration, or intent to participate in another clinical study at any time during the conduct of the study.
• Use of medications for the timeframes specified below, with the exception of hormonal contraceptives and medications exempted by the Investigator on a case-by-case basis because they are judged to interfere with subject safety e.g., topical drug products without significant systemic absorption are permissible:
• Prescription medication within 14 days prior to the first dosing (Part 1); Prescription medication within 14 days prior to the first dosing that in the opinion of the Investigator could impact the subjects safe participation in the study (Part 2)
• Any medication, or treatments, that may affect the immune system such as allergy injections, immunoglobulin, interferon, immunomodulators, cytotoxic drugs, or other drugs known to be frequently associated with significant major organ toxicity within 90 days prior to enrolment;
• Any registered vaccine administered within 30 days prior to enrolment in the study, or who plan to receive any non-study vaccines within 28 days of the second dose of the study vaccine
• Any other investigational coronavirus vaccine i.e. SARS-CoV-1, SARS-CoV-2, MERS etc. at any time prior to, or during, the study.

Sponsors & Collaborators

• The University of Queensland: lead
• Syneos Health: collaborator
• Coalition for Epidemic Preparedness Innovations: collaborator

Study Sites (1)

Nucleus Network Brisbane (Q-Pharm Pty Ltd)

Herston, Queensland, 4007, Australia

Location

Related Publications (2)

• Chappell KJ, Mordant FL, Amarilla AA, Modhiran N, Liang B, Li Z, Wijesundara DK, Lackenby JA, Griffin P, Bennet JK, Hensen L, Zhang W, Nguyen THO, Tran MH, Tapley P, Barnes J, Reading PC, Kedzierska K, Ranasinghe C, Subbarao K, Watterson D, Young PR, Munro TP. Long-term safety and immunogenicity of an MF59-adjuvanted spike glycoprotein-clamp vaccine for SARS-CoV-2 in adults aged 18-55 years or >/=56 years: 12-month results from a randomised, double-blind, placebo-controlled, phase 1 trial. EBioMedicine. 2023 Nov;97:104842. doi: 10.1016/j.ebiom.2023.104842. Epub 2023 Oct 20.

  PMID: 37865043 DERIVED

• Chappell KJ, Mordant FL, Li Z, Wijesundara DK, Ellenberg P, Lackenby JA, Cheung STM, Modhiran N, Avumegah MS, Henderson CL, Hoger K, Griffin P, Bennet J, Hensen L, Zhang W, Nguyen THO, Marrero-Hernandez S, Selva KJ, Chung AW, Tran MH, Tapley P, Barnes J, Reading PC, Nicholson S, Corby S, Holgate T, Wines BD, Hogarth PM, Kedzierska K, Purcell DFJ, Ranasinghe C, Subbarao K, Watterson D, Young PR, Munro TP. Safety and immunogenicity of an MF59-adjuvanted spike glycoprotein-clamp vaccine for SARS-CoV-2: a randomised, double-blind, placebo-controlled, phase 1 trial. Lancet Infect Dis. 2021 Oct;21(10):1383-1394. doi: 10.1016/S1473-3099(21)00200-0. Epub 2021 Apr 19.

  PMID: 33887208 DERIVED

MeSH Terms

Conditions

COVID-19

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

• Paul Griffin, Dr

  Nucleus Network Brisbane

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: Cohort 1: SARS-CoV-2 Sclamp vaccine 5 mcg, or placebo Cohort 2: SARS-CoV-2 Sclamp vaccine 15 mcg, or placebo Cohort 3: SARS-CoV-2 Sclamp vaccine 45 mcg, or placebo

Study Record Dates

• First Submitted: July 13, 2020
• First Posted: August 3, 2020
• Study Start: July 13, 2020
• Primary Completion: April 30, 2024
• Study Completion: April 30, 2024
• Last Updated: May 2, 2024

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: Immediately following publication, no end date
• Access Criteria: Available only to achieve the aims in the approved proposal

Locations

AU (1)