A Randomized, Placebo-controlled Trial, to Evaluate the Safety and Immunogenicity of the COVID-19 Vaccine, a Measles Vector-based Vaccine Candidate Against COVID-19 in Healthy Volunteers Consisting of an Unblinded Dose Escalation and a Blinded Treatment Phase
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- COVID-19
- Sponsor
- Institut Pasteur
- Enrollment
- 90
- Locations
- 2
- Primary Endpoint
- To assess the safety and tolerability of the COVID-19 vaccine following one or two consecutive intramuscular injections in healthy volunteers
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
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).
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Males and females between the ages of 18 and 55 years (at the time of consent).
- •Healthy participant, according to the investigator's clinical judgment, as established by medical history, vital signs, physical examination, and laboratory assessments
- •Participant with a body mass index (BMI) \<30.0 kg/m2
- •Provide written informed consent before initiation of any study procedures.
- •A female participant is eligible for this study if she is not pregnant, given by a negative serum pregnancy test at screening and a negative urine pregnancy test at V1 (1st injection), or breast feeding and 1 of the following:
- •Of non-childbearing potential (i.e., women who have had a hysterectomy or tubal ligation or are postmenopausal, as defined by no menses in greater than or equal to 1 year).
- •Of childbearing potential but has been and agrees to continue practicing highly effective contraception or abstinence (if this is the preferred and usual lifestyle of the participant) from 30 days prior to vaccination up to 6 months after the last injection (D210).
- •Highly effective methods of contraception include 1 or more of the following:
- •male partner who is sterile (vasectomised) prior to the female participants entry into the study and is the sole sexual partner for the female participant;
- •hormonal (oral, intravaginal, transdermal, implantable or injectable);
Exclusion Criteria
- •Subjects actively or previously infected by SARS-CoV-2, as determined by a positive RT-PCR and positive serology test.
- •Subject currently working with high risk of exposure to SARS-CoV-2 (e.g. health care worker, emergency response personnel, etc.) or considered at the investigator's discretion to be at increased risk to acquire SARS-CoV-2 for any other reason.
- •Previous vaccination with an investigational COVID-19 vaccine.
- •History of presence of pulmonary disorders (e.g. COPD, etc.) or asthma.
- •History or present of thrombocytopenia and/or bleeding disorders.
- •A positive serum pregnancy test at screening or urine pregnancy test prior to study injection, women who are planning to become pregnant during the study, or women who are breastfeeding.
- •Clinically relevant history of or current renal, hepatic, gastrointestinal, cardiovascular, respiratory, skin, hematological, endocrine, inflammatory, autoimmune, central nervous system or neurological diseases or clinically relevant abnormal laboratory values.
- •Use of immunosuppressive drugs like e.g. corticosteroids (excluding topical preparations and inhalers) within 3 months prior to the first vaccination or 6 months for chemotherapies and all along the study.
- •A diagnosis of schizophrenia, bipolar disease, or history of hospitalization for a psychiatric condition or previous suicide attempt.
- •A history of treatment for any other psychiatric disorder in the past 3 years that increases the risk to the subject in the opinion of the investigator.
Outcomes
Primary Outcomes
To assess the safety and tolerability of the COVID-19 vaccine following one or two consecutive intramuscular injections in healthy volunteers
Time Frame: up to Day 210
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).
Secondary Outcomes
- 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(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(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.(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(up to Day 42)