General information Section to complete general information about the trial: scientific and public title, protocol identifiers, sponsors and Source(s) of Monetary or Material Support. Scientific title: Adaptive phase I / II clinical trial, randomized, of parallel groups, to evaluate the safety and immunogenicity in adults of two vaccine candidates, based on recombinant RBD subunits for the prevention of COVID-19 in regimens that use the nasal route of administration. (COVID-19) Secondary indentifying numbers: IG/VPIN/CVD19/2001 Issuing authority of the secondary identifying numbers: Center for Genetic Engineering and Biotechnology (CIGB) Primary sponsor: Center for Genetic Engineering and Biotechnology (CIGB), in Havana Secondary sponsor: Not applicable Source(s) of monetary or material support: Center for Genetic Engineering and Biotechnology (CIGB), Havana.
Authorization for beginning Section to complete information about the regulatory approval of clinical trial: regulatory agency name, approval date and reference number in the agency. Regulatory instance to authorize the initiation of the study: Center for State Control of Drugs, Medical Devices and Equipment (CECMED) Reference number: In process
Principal investigator Section to complete information about Email address, telephone number and postal address of the Principal Investigator. First name: Carlos Midle name: Alberto Last name: Gonzalez Delgado Medical Specialty : 2nd degree specialist in Pharmacology; Master in Toxicology; Assistant Researcher. Affiliation: National Toxicology Center (CENATOX) Postal address: Ave 31 y 114, Marianao City: Havana Country: Cuba Zip Code: 11500 Email address: eclinicos@infomed.sld.cu
Clinical sites to participate Section to complete the data related to the clinical sites involved in the trial: site and responsible investigator for every site. Countries of recruitment: Cuba Clinical sites: Not applicable
Recruitment status Section to complete information about the recruitment status and the date of first enrolment subject Recruitment status: Pending Date of first enrollment: 07/12/2020
Health condition and Intervention Section to complete information about the primary medical condition(s) or problem(s) studied and, a characteristics of the intervention(s). Health condition(s) or Problem(s) studied: COVID-19 Health condition(s) code: Disease Prevention Coronavirus Infections SARS Virus Coronaviridae Infections Betacoronavirus Health condition keyword: COVID-19 SARS-CoV2 Intervention(s): Group 1: CIGB-669 (50 µg RBD + 40 µg AgnHB); In each administration (nasal spray) the dose of the product is 200 µL (100 µL for each nostril) corresponding to 50 µg of receptor-binding domain (RBD) recombinant protein and 40 µg of nucleocapsid antigen of the virus. hepatitis B (AgnHB), without adjuvant or preservation; short scheme: 0 (nasal) - 14 (nasal) - 28 (nasal) days. Group 2: CIGB-669 (RBD 50 µg + AgnHB 40 µg) intranasally (nasal spray) 200 µL (100 µL for each nostril); long scheme: 0 (nasal) - 28 (nasal) - 56 (nasal) days. Group 3: CIGB-66 (RBD 50 mcg + aluminum hydroxide 0.30 mg); 0.5 mL intramuscularly in the deltoid region in the 1st dose, followed by another two doses with CIGB-669 (RBD 50 µg + AgnHB 40 µg) intranasally (nasal spray) 200 µL (100 µL for each nostril) ; short scheme: 0 (intramuscular) - 14 (nasal) - 28 (nasal) days. Group 4: CIGB-66 (RBD 50 mcg + aluminum hydroxide 0.30 mg); 0.5 mL intramuscularly in the deltoid region in the 1st dose, followed by another two doses with CIGB-669 (RBD 50 µg + AgnHB 40 µg) intranasally (nasal spray) 200 µL (100 µL for each nostril) ; long scheme: 0 (intramuscular) - 28 (nasal) - 56 (nasal) days. These interventions will be carried out during the first stage (phase I). Subsequently, an intermediate analysis will be carried out where doses and immunization schedules for phase II will be defined. Intervention code: Immunogenicity, Vaccine Immunotherapy, Active Vaccination Nasal Sprays Injections, Intramuscular Administration, Intranasal Intervention keyword: CIGB-669, CIGB-66
Outcomes and Timepoint Section to complete information about primary and secondary outcomes including. It includes the metric or method of measurement used and, the time point for every outcome. Primary outcome(s): 1. Safety - Clinical Adverse Events-AE (They will be measured as: -Occurrence of AE (Yes, No), -Description of AE (name of event), -Intensity of AE (mild, moderate, severe), -Casuality relationship ( unrelated, doubtful, possible, probable, definitive), -Measures adopted (None, Administration of any pharmacological therapy, Addition of a non-pharmacological therapy, Study exit, Hospitalization / prolongation of hospitalization), -Result (Completely resolved, Resolved with sequelae, Conditions in improvement, Condition present and unchanged, Worsening, Death caused by this event)). Measurement time: within 28 days after the application of each dose. 2. Proportion of subjects with seroconversion of anti-RBD IgG antibodies to SARS-CoV-2 (seroconversion will be considered as that ≥ 4 times the initial determination of the antibody titer). Measurement time: on days 14, 28 and 42 (for the short scheme 0-14-28) and 14, 28, 56 and 70 (for the long scheme 0-28-56), with respect to the baseline time. Key secondary outcomes: 1. Specific anti-RBD IgG antibodies (geometric mean). Measurement time: on days 0, 14, 28 and 42 (for the short vaccination schedule: 0-14-28) and 0, 14, 28, 42, 56 and 70 (for the long schedule: 0-28- 56). 2. ACE2 inhibition (by ELISA - Enzyme-linked immunoadsorption assay). Measurement time: on days 0, 28 and 42 (for the short vaccination scheme) and 0, 28, 56 and 70 (for the long scheme). 3. Humoral response of specific anti-RBD IgM antibodies. Measurement time: on days 0, 28 and 42 (for the short vaccination scheme) and 0, 28, 56 and 70 (for the long scheme). 4. Humoral and mucosal response of anti-RBD Antibodies (IgA). Measurement time: at screening and at day 42 for short schedules and at screening and at day 70 for long vaccination schedules for mucosal response. The baseline value in the case of humoral IgA would be t = 0.
Selection criterias Section to complete information about the inclusion and exclusion criteria for participant selection, including age and gender. Gender: Male/Female Minimum age: 19 years Maximum age: 54 years Inclusion criteria: 1) Women and men, 19 to 54 years of age (Phase I) and 19 to 80 years of age (Phase II). 2) Physical examination without clinically significant alterations. 3) Laboratory tests within or outside the reference range, but not clinically significant. 4) Willingness of the subject to participate expressed through the delivery of signed informed consent. Exclusion criteria: 1) History of COVID-19 or current condition of COVID-19 +, confirmed by laboratory PCR and / or rapid test). 2) Contact or suspect of COVID-19 at the time of inclusion. 3) Presence of fever or cough or shortness of breath or anosmia / ageusia, or acute infection during the 15 days prior to the administration of the vaccine candidate or at the time of its application. 4) Decompensated chronic diseases. 5) Those who have been at high risk of exposure: close contacts of confirmed cases of SARS-CoV-2 infection, front-line healthcare professionals for COVID-19 patients working in the ER, ICU and other areas higher risk. 6) Any finding or medical condition in the nostrils that makes it difficult to properly administer the product and follow-up (eg, chronic obstructive allergic rhinitis, obstructive nasal septum deviation, benign and malignant nostril tumors such as polyposis and squamous cell carcinoma). 7) Tattoos in both deltoid regions that make it difficult to observe the injection site, taking into account the random nature of the allocation of treatment. 8) Findings in laboratory tests outside the reference values ??and that are clinically significant. 9) Obesity (BMI ≥ 35 Kg / m2) or underweight (BMI ≤18 Kg / m2) 10) Have previously received a licensed or investigational vaccine, specific for coronavirus. 11) Use of any investigational product (drug or vaccine) within 3 months prior to recruitment, or planned for during the study period. 12) Having been treated within the previous three months or the possibility of requiring treatment during the trial for any underlying condition with: immunomodulators (eg some type of Interferon, Transfer Factor, Biomodulin T, Immunoferon, Thymosin), or with steroids by any route of administration, or with cytostatics. 13) Have received blood, immunoglobulins and / or any blood product within the three months prior to inclusion. 14) Allergy to Thimerosal or any other component of the formulations under study (Allergy to Thimerosal in Phase II is not relevant if the group with CIGB 66 is not selected). 15) History or suspicion of alcoholism or drug dependence. 16) Pregnancy, breastfeeding or willingness to get pregnant during the study. Women of childbearing potential who do not agree to use effective contraception within 3 months after completing the third study dose. 17) Presence of mental and / or psychiatric disorders that make it impossible to sign the informed consent or follow-up of the volunteer. Type of population: Adults Type of participant: Healthy volunteers
Study design Section to complete information about the characteristics of the study design. Type study: Interventional Purpose: Prevention Allocation: Randomized trial Masking: Open Control group: Uncontrolled Study design: Parallel Phase: 1-2 Target sample size: 88
Contact for public queries Section to complete information about Email address, telephone number and postal address of the contact who will respond to general queries, including information about current recruitment status First Name: Zurina Last Name: Cinza Estevez Specialty: 1st degree specialist in Clinical Biochemistry; Master in Clinical Trials. Affiliation: Center for Genetic Engineering and Biotechnology (CIGB). Postal Address: Ave. 31 entre 158 y 190, Cubanacan, Playa. City: Havana Country: Cuba Zip Code: 11300 Telephone: +53-72716022 Email : zurina.cinza@cigb.edu.cu
Contact for scientific queries Section to complete information about Email address, telephone number and postal address of the contact who will respond to scientific queries. First Name: Zurina Last Name: Cinza Estevez Specialty: 1st degree specialist in Clinical Biochemistry; Master in Clinical Trials. Affiliation: Center for Genetic Engineering and Biotechnology (CIGB). Postal Address: Ave. 31 entre 158 y 190, Cubanacan, Playa. City: Havana Country: Cuba Zip Code: 11300 Telephone: +53-72716022 Email : zurina.cinza@cigb.edu.cu
Data Sharing Section to complete the data related to the data sharing plan. Data sharing plan: No
Research Ethics Committees Section to complete the data related to the review ethics committees. Name of Research Ethics Committees: National Toxicology Center (CENATOX) Status of evaluation: Approved Status of evaluation date of Ethic Committee: 20/11/2020 Postal address of Ethic Committee : Avenida 31 y 114, Marianao, Havana, ZC: 11500, Cuba Telephone: - Email: cenatox@infomed.sld.cu
About study completion Section to complete the data related to the study completion. Study completion date: 31/05/2021 Date of available results: 30/06/2021 Date of first publication: 30/07/2021
Registration and Update Section to complete information about the name of Primary Registry, date of registration and the unique ID number assigned by the registry (RPCEC). Primary registry: RPCEC Unique ID number: RPCEC00000345 Date of Registration in Primary Registry: 26/11/2020 Record Verification Date: 2020/11/27 Next update date: 2021/11/27 Link to the spanish version: Click here
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