This is a randomized, placebo-controlled, two center, Phase I trial in healthy adult volunteer participants consisting of two phases, an unblinded dose escalation and a double blind treatment phase to investigate the safety, tolerability and immunogenicity of a novel measles-vector based vaccine candidate against SARS-CoV-2 infection (TMV-083/V-591).
This is a prospective, interventional, randomized, Phase I trial comparing two different dose levels and immunization regimen of a novel COVID-19 vaccine candidate (TMV-083/V-591) against SARS-CoV-2 infection, consisting of two phases, an unblinded dose escalation and a double-blind treatment phase, to assess the safety, tolerability and immunogenicity. 90 subjects will be enrolled, 30 per cohort in three cohorts, each cohort comprising 24 vaccinees and 6 placebo recipients. Subjects will either receive two immunizations with a low dosage vaccine (Cohort A), two immunization with a high dosage vaccine (Cohort B), a single immunization with the high dosage vaccine (Cohort C) or placebo (randomized to all three cohorts). As safety precaution, the study will begin with the enrolment of a small group of 6 sentinel subjects (2 Sentinel Groups, three subjects each of cohorts A and B) each of whom will receive the vaccine on days 0 and 28 in an unblinded and non-randomized manner. Thereafter, 84 remaining participants will be enrolled in a double-blinded, randomized manner into one of the three cohorts (A, B or C). Placebo will be applied to blind the different regimen. After the screening visit, participants will be expected to return to the investigational clinical site for 8 visits (9 for the sentinel groups) up to day 91 for immunogenicity sample collection and up to day 210 for safety assessments. Samples for measles shedding will be collected from subjects of the Sentinel Groups (unblinded regiment in cohort A and B). Body fluids including saliva, nasal swab, urine and whole blood will be collected from day 0 up to day 42. The investigator and site personnel assessing Adverse Events (AEs), all participants, as well as the sponsor's representatives involved in the monitoring and conduct of the study will be unblinded to which vaccine was administered within the unblinded treatment phase. Only the site personnel performing randomization, preparation and administration of Investigational Medicinal Product (IMP) will be unblinded within the randomized double-blinded treatment phase.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
90
Live-attenuated recombinant measles vaccine virus vector expressing a modified surface glycoprotein of the novel Coronavirus (SARS-CoV-2)
Live-attenuated recombinant measles vaccine virus vector expressing a modified surface glycoprotein of the novel Coronavirus (SARS-CoV-2)
SGS Life Sciences, Clinical Pharmacology Unit
Antwerp, Belgium
CIC Cochin - Pasteur
Paris, France
To assess the safety and tolerability of the COVID-19 vaccine following one or two consecutive intramuscular injections in healthy volunteers
Rate of solicited Adverse Event up to 14 days after each injection. Rate of unsolicited AE up to 28 days after the last injection. Rate of serious adverse events (SAEs), serious adverse reactions (SARs), suspected unexpected serious adverse reactions (SUSARs) and adverse events of special interest (AESI) all along the study period (up to Day 210).
Time frame: up to Day 210
To assess induction of SARS-CoV-2 spike protein-binding antibodies upon one or two administrations of the COVID-19 vaccine by means of ELISA up to study day 56
SARS-CoV-2 specific antibodies up to study day 56 as measured by spike protein-specific ELISA and serum neutralization assay
Time frame: Day 56
To assess induction of SARS-CoV-2 neutralizing antibodies upon one or two administrations of the COVID-19 vaccine by means of serum neutralization assay up to study day 91
SARS-CoV-2 specific antibodies up to study day 91 for each cohort as measured by spike protein-specific ELISA and serum neutralization assay
Time frame: Day 91
To assess SARS-CoV-2 spike protein-specific, cell-mediated immune responses up to study day 91, induced by one or two doses of vaccine, by means of intracellular staining and flow cytometry.
SARS-CoV-2 spike protein-specific cell-mediated immune response up to study day 91 induced by one or two doses as measured by intracellular staining and flow cytometry
Time frame: up to Day 91
To assess potential measles virus shedding by means of RT-qPCR of saliva, nasal swab, urine, or blood samples in sentinel groups on day 0 and up to day 42
Occurrence of measles virus shedding as evidenced by a positive RT-PCR for saliva, nasal swab, urine, or blood sample in sentinel groups.
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Live-attenuated recombinant measles vaccine virus vector expressing a modified surface glycoprotein of the novel Coronavirus (SARS-CoV-2) and placebo
Physiological saline solution (0.9% NaCl)
Time frame: up to Day 42