SpiN-Tec MCTI UFMG will be used as a vaccine booster against COVID-19 and will beevaluated using the active comparator, a vaccine approved by ANVISA (Brazilian HealthRegulatory Agency). The study will consist of two parts: Part A) a Phase 1dose-escalation clinical trial to assess safety and reactogenicity; followed by Part B) aPhase 2 clinical trial to assess the safety and immunogenicity of SpiN-Tec. The studywill include healthy participants of both sexes, aged 18 to 85, who have already receivedthe full COVID-19 vaccination schedule with CoronaVac® (Butantan) or Covishield®(AstraZeneca) and who have received one or two booster doses of Covishield® or Comirnaty®(Pfizer's RNA-based vaccine) at least 6 months ago. Participants may or may not have hadnatural SARS-CoV-2 infection.
SpiN-Tec-001 is a multicenter, double-blind, randomized, controlled with active
comparator (Covishield®), escalating dose study to verify the safety and immunogenicity
of the investigational product, SpiN-Tec MCTI UFMG. SpiN-Tec MCTI UFMG is a heterologous
vaccine booster and will be evaluated using the active comparator, Covishield®
(AstraZeneca), as a reference, which will be the homologous or heterologous booster to
the primary vaccination. The study will consist of two parts: Part A) a phase 1
dose-escalation clinical trial to verify the safety and reactogenicity of the
investigational product, followed by Part B) a phase 2 clinical trial to study the safety
and immunogenicity of SpiN-Tec. The study intends to evaluate a booster dose with the
SpiN-Tec MCTI UFMG vaccine in healthy participants of both sexes who have already
received the complete vaccination schedule for COVID-19 with the CoronaVac® (Butantan) or
Covishield® ( AstraZeneca) and who have received one or two booster doses of Covishield®
or Comirnaty® (Pfizer's RNA-based vaccine) for at least 6 months. Participants may or may
not have had a natural infection with SARS-CoV-2. The participants' last antigenic
stimulation (boost or infection) must have occurred at least 6 months before
randomization in the study. Part A (Phase 1): double-blind, randomized (within the same
arm) clinical trial in an escalating dose and controlled with an active comparator to
verify the safety of SpiN-Tec MCTI UFMG. For this part, participants who have completed
the vaccination schedule with CoronaVac® and have received a single booster dose with
Comirnaty® (Pfizer) between 9 and 15 months of inclusion and who have no history of
COVID-19. The study includes 24 participants in each of the 3 arms, based on the doses of
SpiN-Tec MCTI UFMG, and each arm consists of two age groups. Furthermore, this is a
sentinel group within each arm: Arm 1 - 20 µg of SpiN-Tec MCTI UFMG (N=18) or active
comparator (N=6): 18 participants (9 participants aged 18 to 54 years and 9 participants
in the age group of 55 to 85 years) receiving 1 dose of the SpiN-Tec MCTI UFMG vaccine
with 20 micrograms and 6 participants (3 participants in the age group of 18 to 54 years
and 3 participants in the age group of 55 to 85 years ) will receive 1 dose of the active
comparator. The sentinel group is the first three individuals recruited from the youngest
age group. Two of these individuals received SpiN-Tec MCTI UFMG, and the other
individual, the active comparator, was randomized blindly and observed for at least 7
days before continuing vaccination in the corresponding age group. Arm 2 - 60 µg of
SpiN-Tec MCTI UFMG (N=18) or active comparator (N=6): 18 participants (9 participants
aged 18 to 54 years and 9 participants aged 55 to 85 years) receive 1 dose of the
SpiN-Tec MCTI UFMG vaccine with 60 micrograms and 6 participants (3 participants aged 18
to 54 years and 3 participants in the age group 55 to 85 years) will receive 1 dose of
the active comparator. The sentinel group is the first three individuals recruited from
the youngest age group. Two of these individuals receive SpiN-Tec MCTI UFMG, and the
other individual, the active comparator, is blindly randomized and observed for at least
7 days before continuing vaccination in the corresponding age group. Arm 3 - 100 µg
SpiN-Tec MCTI UFMG (N=18) or active comparator (N=6): 18 participants (9 participants
aged 18 to 54 years and 9 participants aged 55 to 85 years) receive 1 dose of the
SpiN-Tec MCTI UFMG vaccine with 100 micrograms and 6 participants (3 participants aged 18
to 54 years and 3 participants aged 55 to 85 years) will receive 1 dose of the active
comparator. The sentinel group is the first three individuals recruited from the youngest
age group. Two of these individuals receive SpiN-Tec MCTI UFMG, and the other individual,
the active comparator, is blindly randomized and observed for at least 7 days before
continuing vaccination in the corresponding age group. All participants in the sentinel
cohorts in Part A are under observation at the Research Center for at least 60 minutes
after vaccine administration. The remaining participants are under observation for at
least 30 minutes. All participants in Part A are monitored for 360 days with regular
clinical assessments through Telephone contact on days 1, 3, 10, and 21 and then monthly
until the end of the study, except when there is an in-person visit. The sentinel cohort
has additional contact on day 5. In-person return on days 7, 14, 28, 90, 180, 270 and 360
after vaccination. Participants are recruited and allocated sequentially to arms 1, 2,
and 3 of the study, respectively receiving doses of 20 ug, 60 ug, and 100 ug of the
investigational product, and, in each age group of each arm, 9 participants receive the
SpiN-Tec MCTI UFMG vaccine and 3 active comparator, totaling 12 participants for the
younger age group (18-54 years) and 12 participants for the older age group (55-85
years). Of these, 18 participants received reinforcement with SpiN-Tec MCTI UFMG, and 6
received reinforcement with the active comparator. The first group recruited volunteers
aged 18 and 54 to administer the lowest dose (20 µg) of SpiN-Tec MCTI UFMG. The first
three randomized subjects in this age group are the sentinel group and observed for at
least 7 days before continuing vaccination in that arm.
Adverse events (AEs) of the sentinel cohort are evaluated by the protocol and safety
review team (TRPS) within 7 days of vaccination, and if no study suspension criteria are
met, vaccination for the remainder of the arm is proceeded. After the first 14 days of
follow-up for all individuals in this age group, a new blinded safety analysis will be
carried out by TRPS for the dose and age group escalation decision. If no criteria for
suspension of the study are found, the TRPS must recommend continuing the study. If any
criterion for stopping the study is observed, or if a member of the TRPS deems it
necessary, a meeting with an independent safety monitoring committee (CIMS) must be
requested. If consulted, CIMS will receive the safety data and must recommend continuing
the study as planned, suggesting changes to the protocol, or recommending stopping the
study. This procedure must be repeated for each dose escalation or age group. If the TRPS
recommendation is to continue the study, volunteers from the same arm aged between 55 and
85 years will be randomized. Likewise, individuals between 18 and 54 in Arm 2 (60 ug of
SpiN-Tec MCTI UFMG) will be vaccinated, with the first three individuals in Arm 2 making
up the sentinel cohort and will be observed for 7 days before continuing randomization of
that same arm. After completion of the first 14 days of follow-up in the youngest age
group of Arm 2, a safety analysis by TRPS will be performed to decide on dose escalation
(Arm 3) and age group 55-85 years (Arm 2). Likewise, the first three subjects in Arm 3
will be from the sentinel cohort and observed for 7 days before continuing vaccinations
in that arm. Before lane escalation for Arm 3, a TRPS safety analysis must be carried
out, as occurred in the other arms. At the end of the V28 visit of the last randomized
participant in Part A, a blinded interim analysis of safety data and preliminary
immunogenicity data (neutralizing antibodies against the ancestral strain and relevant
VoCs at the time of the study, binding antibodies and IFNg production) should be
performed and carried out before the study continued. CIMS will receive safety and
preliminary immunogenicity data for analysis.
The Sponsor will suggest a dose for Part 2 of the study based on safety data and
preliminary immunogenicity data that the study Scientific Committee and CIMS must
previously approve. The dose with the best preliminary immunogenicity performance
associated with the lowest intensities and frequencies of AEs will be chosen. Part B:
after the interim analysis of the results obtained in Part A and approval by ethical
regulatory bodies, the chosen dose of SpiN-Tec MCTI UFMG will be used as a vaccine
booster for participants in the experimental arm of Part B of the study. The vaccination
booster is very advanced in Brazil, reaching more than 80% of the population vaccinated
so far (September 2022), and could be at even higher levels when the study begins.
Therefore, recruitment will seek to include individuals who have received a booster
(either one or two doses). Thus, in this study phase, an additional 180 participants who
will receive the SpiN-Tec MCTI UFMG vaccine will be recruited, and another 180
participants will receive the active comparator. At least 30% of Part B participants must
be between 55 and 85. Therefore, the study arms in Part B will be: Arm 1: reinforcement
with SpiN-Tec MCTI UFMG, 180 individuals, 30% of whom are between 55 and 85 years old.
Arm 2: reinforcement with Covishield®, 180 individuals, 30% from the age group between 55
and 85 years old. All participants in Part B will be under observation at the Research
Center for at least 30 minutes after vaccine administration and will be monitored for 360
days with regular clinical assessments through Telephone contact on days 1, 3, 10, 21,
and then monthly until the end of the study, except in the months when there will be an
in-person visit. In-person return on days 7, 14, 28, 90, 180, 270 and 360 after
vaccination. Therefore, the study will recruit a total of 432 participants, with 72
participants in Part A and 360 participants in Part B. After all participants in Part B
complete 70 days of follow-up after the vaccine, after contact C70, there will be a break
in the blinding and analysis of safety and immunogenicity data to verify the primary
outcome of Part B. From that point on, the study is no longer double-masked, and
participants continue to be monitored for safety purposes.
Biological: SpiN-Tec MCTI UFMG
Chimeric recombinant protein (SpiN) adjuvanted with CTVad1
Other: Active Comparator: Covishield® vaccine
active comparator using vaccine approved by ANVISA (Brazilian Health Regulatory Agency)
Other: Active Comparator: Comirnaty® vaccine
active comparator using vaccine approved by ANVISA (Brazilian Health Regulatory Agency)
Inclusion Criteria:
Part A: Healthy individuals aged 18 to 54 with completed primary vaccination schedule for
COVID-19 with CoronaVac®. Have received a booster dose with Comirnaty® between 9 and 15
months before inclusion in the study.
Part A2: Healthy individuals aged 55 to 85 with a completed vaccination schedule for
COVID-19 with CoronaVac® or Covishield® for at least six months from inclusion in the
study. Have received at least one booster dose with Comirnaty® or Covishield® at least
six months ago.
Part B: Healthy individuals aged 18 to 85 who completed the vaccination schedule for
COVID-19 with CoronaVac® or Covishield® for at least six months from inclusion in the
study. Have received at least one booster dose with Comirnaty® or Covishield® at least
six months ago.
All Parties: Consent to the study and its procedures, documented by signing the Free and
Informed Consent Form (TCLE). Present good general health as determined by medical
examination. Women of childbearing potential must agree to use acceptable contraception*
for at least 30 days before initiation of vaccination and at least 90 days following the
use of the investigational product or active comparator. Agree not to donate blood while
participating in the study.
Acceptable contraceptive methods: Barrier methods, including condoms or cervical caps.
Surgically sterile partner/participant (including those undergoing vasectomy,
hysterectomy, bilateral oophorectomy, and or tubal ligation) who is the only partner.
Intrauterine device (with or without hormones) implanted. Birth control medications
(oral, topical, injectable, or implantable). True sexual abstinence is in line with the
patient's preferred and usual lifestyle. Note: periodic abstinence, such as calendar,
ovulation, symptothermal, post-ovulation, or coitus interruptus methods, will not be
considered a valid method.
Exclusion Criteria:
Part A: No previous history or acute infection with SARS-CoV-2. Previous records will be
considered self-declaration by the participant. Vaccination booster for COVID-19 less
than nine months ago and more than 15 months after inclusion in the study. The presence
of comorbidities or any condition that, in the study investigator's assessment, could put
the participant at risk or create a confounding factor in the study, including clinically
stable chronic diseases.
Part A2: Acute SARS-CoV-2 infection or less than six months from the date of inclusion in
the study. Vaccination booster for COVID-19 less than six months ago. The presence of
comorbidities or any condition that, in the study investigator's assessment, could put
the participant at risk or create a confounding factor in the study, including clinically
stable chronic diseases.
Part B: Acute or SARS-CoV-2 infection or less than six months from the date of inclusion.
Vaccination booster for COVID-19 less than six months ago. Any condition that, in the
assessment of the study investigator, could put the participant at risk or create a
confounding factor in the study. Diseases such as diabetes, hypertension, and clinically
stable neuralgia may not constitute an exclusion criterion as determined by the medical
investigator.
All Parties: Have received primary vaccination with Janssen or Comirnaty® vaccine. Have
received a booster vaccine with the Janssen or CoronaVac® vaccine. History of SAE after
administration of a COVID-19 vaccine. History of thrombophilia. Being on anticoagulant
therapy or having a bleeding disorder that contraindicates intramuscular injection.
Positive serology for HIV, HBV (HBsAg) or HCV. Laboratory abnormality in blood count,
biochemistry, or urine tests. Exception will be defined by the clinical investigator when
evaluated together with the participant's medical history. Women who are pregnant,
breastfeeding, or intend to become pregnant/breastfeed within three months of inclusion
in the study. Evidence of clinically active disease such as, but not limited to:
neurological, renal, cardiovascular, endocrine, pulmonary, hepatic, hematological,
immunological (including autoimmunities and immunodeficiencies), neoplastic or infectious
disease. Psychiatric illness or cognitive impairment that, in the investigator's
judgment, may affect the participant's ability to engage in the clinical trial following
the established agenda. Alcohol abuse or use of illicit drugs in the last 12 months
before recruitment has caused any family, medical, or professional problems. History of
severe allergic reaction or anaphylaxis to any component of the vaccine. History of
asplenia. Have participated in any other experimental clinical trial in the 12 months
before inclusion or intend to participate in any experimental clinical trial in the 12
months following participation. Plans to participate in other clinical studies
concurrently with this one. Use of some immunosuppressive therapy three months before
recruitment or planning its use within three months after vaccination, including use of
corticosteroids or other immunosuppressive medication (note: the immunosuppressive dose
of corticosteroids is equivalent to 20 mg/day of prednisone per more than a week (topical
or nasal corticosteroids are not considered immunosuppressive). Use of blood products
(blood or immunoglobulins) within three months before inclusion or indication of their
use during the study. Suspected active infection or confirmed fever (axillary temperature
≥ 38.0 oC) within 72 hours before inclusion. Recruitment should be delayed until the
participant remains fever-free for 72 hours. Have received any live attenuated or
inactivated vaccine within 28 days or 14 days, respectively, before use of the
investigational product or active comparator or planning immunization within 28 days of
study inclusion. History of use of medication authorized by ANVISA intended to prevent or
treat COVID-19 less than six months before the study's inclusion date.
Faculdade de Medicina da UFMG - Unidade de Pesquisa Clínica em Vacinas (UPqVac)
Belo Horizonte 3470127, Minas Gerais 3457153, Brazil
Ricardo T Gazzinelli, DVM, PhD, Study Chair
Vaccine Technology Center (CT Vacinas)