Clinical trial NCT05016934: Evaluation of Safety and Immunogenicity of a Novel Vaccine for Prevention of Covid-19 in Adults Previously Immunized
Official title: Randomized Controlled-trial to Evaluate Safety, Immunogenicity and Efficacy of a Vaccine Composed of a Recombinant S1 Antigen for Prevention of Covid-19 in Adults Previously Fully Immunized With Other Vaccines
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Covid19
Lead sponsor: Hospital do Coracao
Sponsor class: OTHER
Collaborators: name: Farmacore Biotecnologia Ltda
First posted: 2021-08-23
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Randomized controlled trial to evaluate safety, immunogenicity and efficacy of three different doses (10, 25 and 50 mcg) of a novel vaccine compared with placebo in adult volunteers previously immunized against Covid-19 with other vaccines \[Corona Vac (Sinovac), ChAdOx1 (AZ 1222, Astra Zeneca) or Ad26.Co2.S (Janssen)\].

Detailed description: This is a double-blind, randomized controlled trial to evaluate the safety, immunogenicity and efficacy of an investigational vaccine against Covid-19 in adult volunteers previously fully immunized against Covid-19 with other vaccines \[Corona Vac (Sinovac), ChAdOx1 (AZ 1222, Astra Zeneca) or Ad26.Co2.S (Janssen)\].

Three different antigen doses of a vaccine composed of a recombinant S1 antigen, a subunit of SARS-CoV-2 virus S protein, will be compared against placebo to evaluate its efficacy, immunogenicity and preliminary efficacy. The study will consist of three cohorts and a total of 360 participants. Each cohort will be consisted of 120 individuals, who will be randomized in a 2:1 fashion for a vaccine composed of a recombinant S1 antigen or placebo. In the first cohort, participants will be randomized to two applications of 10mcg of a vaccine composed of a recombinant S1 antigenor placebo 28 days apart. In the first week of the study, only three volunteers will be enrolled in order to assess the safety of the vaccine after 7 days by an independent Data and Safety Monitoring Board (DSMB). The other 117 participants will be randomized only if there were no safety concerns on these three first enrolled volunteers. After the enrollment of the first 60 participants, 7-day safety data will be reviewed by the DSMB, who will decide on trial continuation sequence. If there were no safety concerns, the second cohort will start. In the second cohort, participants will be randomized to two applications of 25mcg of a vaccine composed of a recombinant S1 antigen or placebo 28 days apart. This cohort will have the same design and evaluation of safety performed on the first cohort. Again, after the enrollment of the first 60 participants, 7-day safety data will be reviewed by the DSMB, who will decide on trial continuation sequence. If there were no safety concerns, the third cohort will start. In the second cohort, participants will be randomized to two applications of 50mcg of a vaccine composed of a recombinant S1 antigen or placebo 28 days apart.

The primary endpoint of safety will be evaluated on day 7 after the first and second application of the vaccine. Therefore, all participants will have this endpoint assessed 36 days after the enrollment. The secondary endpoints will be immunogenicity, evaluated at days 29 (I.e., 28 days after the first dose) and 43 (I.e., 14 days after the second dose), and efficacy, evaluated as the incidence of symptomatic laboratory confirmed cases of Covid-19 from 14 days after the second dose until 12 months after enrollment.

A sample size was calculated based on the probability of adverse events. Assuming a 2.5% incidence of adverse events, a study with 240 participants receiving the active drug would have a probability higher than 99% to recognize at least one adverse event. Assuming a 5% incidence of adverse events, a study with 80 participants receiving the different doses (10, 25 and 50mcg) of the active drug would have a probability of 98% to recognize at least one adverse event.

As mentioned before, an independent DSMB will review safety after the enrollment of the first three participants in each cohort and again after the enrollment of the first 60 participants in each cohort. Pre-specified guidelines will be established to recommend early stopping of the trial for evidence of harm.

Eligibility criteria: Inclusion Criteria:

* Signed informed consent
* Previously totally immunized, I.e., two doses for Corona Vac (Sinovac) or ChAdOx1 (AZ 1222, Astra Zeneca, and one dose for Ad26.Co2.S (Janssen) vaccines at least three months before enrollment
* Negative RT-PCR for SARS-CoV-2 at the moment of triage
* No previous history of laboratory confirmed Covid-19

Exclusion Criteria:

* Pregnancy
* Participation in other vaccine trial
* Active decompensated chronic condition, namely, cardiovascular, respiratory, neurological, metabolic or hepatic diseases
* Any immunocompromise condition (primary immunodeficiencies, auto-immune diseases, long-term use of corticosteroids, solid organ transplant recipients, hematopoietic stem-cell transplant recipients, human-immunodeficiency virus active infection)
* Active cancer
* Hepatitis B or C
* History of allergic reactions to any vaccine component, including excipients and preservatives (neomycin, streptomycin, polymyxin B, eggs
* Blood donation in the past 4 weeks before screening
* Received blood product in the past 3 months before screening

Primary outcomes:
measure: Frequency and severity of local and systemic adverse events
timeFrame: From day 1 until day 7 after each vaccine or placebo administration
measure: Frequency and severity of adverse events of special interest
timeFrame: From day 1 until day 43
Secondary outcomes:
measure: Quantification of interferon gamma producing T lymphocytes (INF-γ) in specific response
timeFrame: At days 29, 43, 91, 181 and 366
measure: Total quantification of CD4 and CD8 T lymphocytes specific to the S1 peptide library
timeFrame: At days 29, 43, 91, 181 and 366
measure: Quantification of CD4 and CD8 T lymphocytes producing specific Th1 (INF-γ, tumor necrosis factor (TNF-α) and IL-2) and Th2 (IL-4, IL-10 and IL-13) intracellular cytokines to the S1 peptide library
timeFrame: At days 29, 43, 91, 181 and 366
measure: Geometric mean titer (GMT) of IgG antibody to protein S1 compared to placebo
timeFrame: At days 29, 43, 91, 181 and 366
measure: Percentage of subjects with virus neutralizing antibody (NAb) in all vaccinated cases compared to placebo
timeFrame: At days 29, 43, 91, 181 and 366
measure: Incidence of new cases of symptomatic laboratory confirmed by RT-PCR for SARS-CoV-2
timeFrame: From day 43 to day 366
Other outcomes:
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