Study to Assess Safety, Reactogenicity and Immunogenicity of the VACCINE RNA MCTI CIMATEC HDT (HDT-301) Vaccine Against COVID-19

NCT04844268 | Unknown Phase 1 DMC

• 1 other identifier: CIMATEC01
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase I, double-blind, placebo-controlled,dose-ranging clinical trial in healthy males and non-pregnant females, 18 to 55 years of age. The trial is designed to assess the safety, reactogenicity, and immunogenicity of VACCINE RNA MCTI CIMATEC HDT(HDT-301), which is a novel Lipid-Inorganic Nanoparticle (LION) formulated replicating RNA-based vaccine that encodes for a full-length spike (S) protein of the SARS-CoV-2 virus. As a replicating mRNA vaccine, VACCINE RNA MCTI CIMATEC HDT(HDT-301) has the potential to allow the advantages of dose sparing, and possibly administration as a single dose, compared with other mRNA platforms. Enrollment will occur at one domestic site. A total of 90 healthy subjects will receive multiple dosages of intramuscular (IM) injections of VACCINE RNA MCTI CIMATEC HDT(HDT-301). Participants will be enrolled sequentially in three dose cohorts (cohort 1 = 1 µg, cohort 2 = 5 µg, and cohort 3 = 25 µg), with each cohort consisting of a total of 30 subjects. Within each dose cohort, participants will be randomized (4:1 ratio for active vaccine:placebo) with equal probability of receiving a schedule of two doses, of the same concentration, on days 1 and 28 (group 1) or 1 and 56 (group 2), or a schedule of single dose administration (group 3) VACCINE RNA MCTI CIMATEC HDT(HDT-301). The main objective is to evaluate the safety and reactogenicity of 3 dose vaccination schedule of VACCINE RNA MCTI CIMATEC HDT(HDT-301) and 1 dose of placebo in healthy adults. Safety and tolerability will be the primary endpoint assessed by incidence of adverse events for each dose through 12 months after the vaccination. Scheduled interim immunogenicity evaluations will be conducted for pre-specified timepoints as secundary and exploratory endpoints.

Conditions

SARS-CoV-2

Outcome Measures

Primary Outcomes (2)

• Safety and tolerability of a schedule of 2 administrations and a schedule of one administration of VACCINE RNA MCTI CIMATEC HDT

  Incidence of adverse event, serious adverse event, adverse event of special interest and adverse event that requires medical evaluation

  day 1 and 28 days after the each vaccination until day 84

• Reactogenicity of a schedule of 2 administrations and a schedule of one administration of VACCINE RNA MCTI CIMATEC HDT .

  local and sistemic adverse events, laboratorial anormalities

  Day 2 and 7 after each vaccination

Secondary Outcomes (4)

• Immunogenicity of a schedule of 2 administrations and a schedule of one administration of VACCINE RNA MCTI CIMATEC HDT (IgG)

  During 12 months of follow up

• Immunogenicity of a schedule of 2 administrations and a schedule of one administration of VACCINE RNA MCTI CIMATEC HDT (neutralizing antibodies)

  During 12 months of follow up

• mmunogenicity of a schedule of 2 administrations and a schedule of one administration of VACCINE RNA MCTI CIMATEC HDT : proportion of IgG antibodies titers

  Day 1 (cohort 1, 2 and 3), day 29 (cohort 1), day 57 (cohort 2) and 28 days after the second vaccination ( cohort 1: day 57 and cohort 2: day 85)

• Immunogenicity of a schedule of 2 administrations and a schedule of one administration of VACCINE RNA MCTI CIMATEC HDT: proportion of specific neutralizing antibodies titers

  Day 1 (cohort 1, 2 and 3), day 29 (cohort 1), day 57 (cohort 2) and 28 days after the second vaccination ( cohort 1: day 57 and cohort 2: day 85)

Other Outcomes (3)

• Immunogenicity of a schedule of 2 administrations and a schedule of one administration of VACCINE RNA MCTI CIMATEC HDT (IgM, IgA and IgG subtipes)

  During 12 months of follow up

• Immunogenicity of a schedule of 2 administrations and a schedule of one administration of VACCINE RNA MCTI CIMATEC HDT (IgM, IgA and IgG subtipes): proportion

  Day 1, 8,29,57,85,114, 180 and 365 for all cohorts. Day 36 for cohort 1 and 64 for cohort 2

• Immunogenicity of a schedule of 2 administrations and a schedule of one administration of VACCINE RNA MCTI CIMATEC HDT : T cells response

  Day 1, 8,29,57,85,114, 180 and 365 for all cohorts. Day 36 for cohort 1 and 64 for cohort 2

Study Arms (4)

Cohort 1

EXPERIMENTAL

Intramuscular (IM) injection of VACCINE RNA MCTI CIMATEC HDT(HDT-301) at a dose of 1 µg. Participants will be randomized (4:1 ratio for active vaccine:placebo) with equal probability of receiving a schedule of two doses, of the same concentration, on days 1 and 28 (group 1) or 1 and 56 (group 2), or a schedule of single-dose administration (group 3).

Biological: Cohort 1 VACCINE RNA MCTI CIMATEC HDT (HDT-301) vaccine; Biological: Placebo

Cohort 2

EXPERIMENTAL

Intramuscular (IM) injection of VACCINE RNA MCTI CIMATEC HDT(HDT-301) at a dose of 5 µg. Participants will be randomized (4:1 ratio for active vaccine:placebo) with equal probability of receiving a schedule of two doses, of the same concentration, on days 1 and 28 (group 1) or 1 and 56 (group 2), or a schedule of single-dose administration (group 3).

Biological: Cohort 2 RNA VACCINE MCTI CIMATEC HDT(HDT-301) vaccine; Biological: Placebo

Cohort 3

EXPERIMENTAL

Intramuscular (IM) injection of VACCINE RNA MCTI CIMATEC HDT(HDT-301) at a dose of 25 µg. Participants will be randomized (4:1 ratio for active vaccine:placebo) with equal probability of receiving a schedule of two doses, of the same concentration, on days 1 and 28 (group 1) or 1 and 56 (group 2), or a schedule of single-dose administration (group 3).

Biological: Cohort 3 VACCINE RNA MCTI CIMATEC HDT(HDT-301) vaccine; Biological: Placebo

Placebo

PLACEBO COMPARATOR

Intramuscular (IM) injection of saline (0.9% sodium chloride). Participants will be randomized (4:1 ratio for active vaccine:placebo) with equal probability of receiving a schedule of two doses, of the same concentration, on days 1 and 28 (group 1) or 1 and 56 (group 2), or a schedule of single-dose administration (group 3).

Biological: Placebo

Interventions

Cohort 1 VACCINE RNA MCTI CIMATEC HDT (HDT-301) vaccine BIOLOGICAL

Intramuscular injections of 1 µg of novel Lipid-Inorganic Nanoparticle (LION) formulated replicating RNA-based vaccine (VACCINE RNA MCTI CIMATEC HDT (HDT-301)) at a dose of 1 µg on days 1 and 28 (group 1) or 1 and 56 (group 2), or a schedule of single dose administration (group 3).

Cohort 1

Cohort 2 RNA VACCINE MCTI CIMATEC HDT(HDT-301) vaccine BIOLOGICAL

Intramuscular injections of 5 µg of novel Lipid-Inorganic Nanoparticle (LION) formulated replicating RNA-based vaccine (VACCINE RNA MCTI CIMATEC HDT(HDT-301)) at a dose of 5 µg on days 1 and 28 (group 1) or 1 and 56 (group 2), or a schedule of single dose administration (group 3).

Cohort 2

Cohort 3 VACCINE RNA MCTI CIMATEC HDT(HDT-301) vaccine BIOLOGICAL

Intramuscular injections of 25 µg of novel Lipid-Inorganic Nanoparticle (LION) formulated replicating RNA-based vaccine (VACCINE RNA MCTI CIMATEC HDT(HDT-301)) at a dose of 25 µg on days 1 and 28 (group 1) or 1 and 56 (group 2), or a schedule of single dose administration (group 3).

Cohort 3

Placebo BIOLOGICAL

Intramuscular (IM) injection of saline (0.9% sodium chloride) on days 1 and 28 (group 1) or 1 and 56 (group 2), or a schedule of single dose administration (group 3), in each cohort.

Cohort 1; Cohort 2; Cohort 3; Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• i. Men and women ≥ 18 years to ≤ 55 years of age; ii. Must be generally healthy as confirmed by a medical history and physical examination for study entry; iii. Subjects who have not been previously immunized with any SARS-CoV-2 vaccine OR subjects who have been immunized with SARS-CoV-2 vaccine based inactivated virus technology at least 3 months from the administration of the second dose and have neutralizing antibody titers less than or equal to 40% in plasma samples tested at 1:40 dilution; iv. Women of childbearing age and of childbearing potential must present during the screening period and on the day of each vaccination the result of a pregnancy test (serum test) with a negative result, as well as not be breastfeeding; in addition, to enroll in the study as volunteers, women who have sex with men must necessarily use one of the contraceptive methods listed below at the time of enrollment and up to 60 days after the last injection of the vaccine (this 60-day interval has been defined as a safety criterion): hormonal (e.g., oral, transdermal, intravaginal, implant, or injection); double barrier (i.e., condom, diaphragm, or cervical cap with spermicide); intrauterine device (IUD) or intrauterine system (IUS); vasectomized (6 months minimum) or abstinent partner; bilateral tubal ligation (if no conception post-procedure); tubal occlusion or bilateral salpingectomy. These precautions are necessary because of unknown effects that Vaccine RNA MCTI CIMATEC HDT may cause in a fetus or newborn. Women will be considered out of the potential to become pregnant if they are postmenopausal (defined as spontaneous amenorrhea of at least 12 months and confirmed with follicle-stimulating hormone concentrations \>40 mUI/ml) or have documented hysterectomy and/or oophorectomy; and, non-sterile men who agree to use adequate contraception with their partner during and up to 60 days after the last injection of the study vaccine; v. The following laboratory test values for screening must be within normal limits or not clinically significant, as determined by the Researcher and approved by the Medical Monitor: sodium, potassium, Glutamic-Oxalacetic Transaminase (GOT), Glutamic-Pyruvic Transaminase (GPT), total bilirubin, alkaline phosphatase, creatinine, fasting glucose, total WBC, hemoglobin, and platelet count. Abnormal results may be repeated once for confirmation at the discretion of the Researcher; vi. The following serological tests must be negative: HIV 1/2 antibody, hepatitis B surface antigen (HBsAg) and hepatitis C virus (HCV) antibody; vii. Negative test for recreational drugs and alcohol according to the standards of the Clinical Research Unit; viii. Normal or not clinically significant urine test as determined by the clinician or designee. Abnormal results may be repeated at the discretion of the Researcher; ix. Must present blood count within normal limits up to 10 days prior to administration of the first dose of the Vaccine RNA MCTI CIMATEC HDT; x. Must present negative RT-PCR test for SARS-CoV-2 24 to 48 h before administration of the study vaccine and absence of signs and symptoms compatible with COVID-19 (e.g. fever, cough, shortness of breath, chills, etc.); xi. Must be able to complete the Mnemonic Adverse Event Questionnaire (MMEA) (Appendix 1); xii. Must give informed consent, be able and willing to make all evaluation visits, be accessible by phone or personal contact by the local study team, and have a permanent address.

You may not qualify if:

• Individuals who meet ANY of the following criteria below will be excluded from the study (ineligible).
• i. Participation in another experimental protocol and/or receipt of any investigational product within the last 3 months prior to screening; ii. Individuals infected with SARS-CoV-2 confirmed by RT-PCR; iii. Treatment with immunosuppressive drugs (e.g., oral or injectable steroidal anti-inflammatory drugs, such as prednisone, or high-dose inhalation) or cytotoxic therapies (e.g., chemotherapeutic drugs or radiation) within the last 6 months prior to screening; iv. Individuals who have received transfusion of blood, plasma, or immunoglobulins in the last 3 months prior to screening; v. Donation of blood products (platelets, whole blood, plasma, etc.) in the last month before screening (1 month before screening); vi. Received any vaccinations in the last month before screening or have any immunizations planned during the study, with the exception of seasonal influenza vaccine, which can be given after 30 days after the second injection of the study; vii. Individuals who have been immunized with any vaccine for SARS-CoV-2 at any time who have neutralizing antibody titers greater than 40% in plasma samples tested at 1:40 dilution; viii. History of autoimmune disease or other causes of immunosuppressive states; ix. History of any other acute or chronic disease (including cardiovascular, pulmonary, neurological, hepatic, rheumatic, hematological, metabolic or renal disorders, uncontrolled hypertension) or use of medications that, in the opinion of the Principal Investigator, may interfere with the safety or immunogenicity evaluation of the vaccine; x. Skin rash, tattoos or any other dermatological condition that may adversely affect the vaccine injection site or interfere with its evaluation; xi. BMI ≥ 32; xii. Hypertension (systolic \> 150 or diastolic \> 95); xiii. History of significant psychiatric illness with current medication use; xiv. Known or suspected alcohol or drug abuse in the last 6 months prior to screening; xv. Chronic tobacco user (\> 20 packs/year); xvi. Individuals with a history of prior anaphylaxis or severe allergic reaction to unknown vaccines or allergens; xvii. Individuals unlikely to cooperate with the requirements of the study protocol.

Sponsors & Collaborators

• SENAI CIMATEC: lead

Study Sites (1)

Hospital da Bahia

Salvador, Estado de Bahia, 41810011, Brazil

RECRUITING

MeSH Terms

Interventions

repRNA-CoV2S vaccine; Vaccines

Intervention Hierarchy (Ancestors)

Biological Products; Complex Mixtures

Study Officials

• Roberto Badaró, PhD

  Principal Investigator

  PRINCIPAL INVESTIGATOR

• Steven Reed, PhD

  Study collaborator

  STUDY CHAIR

Central Study Contacts

Bruna Machado, PhD

CONTACT

55 (71) 3879.5624 / 5267; brunam@fieb.org.br

Carolina Macedo, PhD

CONTACT

55 (71) 3879.5624 / 5267; carolthemacedo@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Blinding was done to all cohorts. Subjects, clinical study staff, statisticians, and investigators were masked to treatment assignment. Laboratory staff that manipulates the vaccine and the placebo were not blinded. Subjects received injections of either vaccine or placebo, delivered in the deltoid muscle in accordance with the study protocol. In order to internal contents were not differentiated, the injections were applied with opaque syringes.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2021
• First Posted: April 14, 2021
• Study Start: January 13, 2022
• Primary Completion: September 1, 2022
• Study Completion: October 1, 2022
• Last Updated: April 4, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)