Double-blind, Comparative, Randomized, Placebo-controlled Study on Immunogenicity, Reactogenicity and Safety of Live Cell-based Vaccine Against Smallpox and Other Orthopoxvirus Infections (VACΔ6 Vaccine) in Volunteers Aged 18-60 Years
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Smallpox
- Sponsor
- Federal Budgetary Research Institution State Research Center of Virology and Biotechnology "Vector"
- Enrollment
- 334
- Locations
- 2
- Primary Endpoint
- Changes in the percentage of vaccinees with a titer of virus-neutralizing antibodies to vaccinia virus ≥1:40, at specified time intervals.
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
The Aim:
Study immunogenicity, confirm the safety and tolerability of different schedules of vaccination with "live cell-based vaccine against smallpox and other orthopoxvirus infections (VAC∆6 vaccine) based on vaccinia virus" using a complex of clinical and laboratory-instrumental techniques.
The research tasks are to:
- To study the immunological activity of a single VAC∆6 vaccine dose of 1x10⁷ plaque-forming units (PFU).
- To study the immunological activity of two VAC∆6 vaccine doses (given 28 days apart) of 1x10⁶ PFU.
- Assess the safety of different VAC∆6 vaccination schedules using a set of clinical and laboratory-instrumental techniques (thermometry, measurement of blood pressure, heart and lung auscultation, ECG, common blood and urine tests, biochemical, immunological and virological studies).
- Assess the reactogenicity of different VAC∆6 vaccination schedules (number of local and systemic reactions, the percentage of those vaccinated with systemic and local reactions of various severity degrees).
- To identify VAC∆6 vaccine-associated adverse events.
- Study cell-mediated immunity induced by different VAC∆6 vaccination schedules.
- Determine the presence of the virus in specific skin formations (crusts, pustules), saliva, blood and urine.
- Evaluate the protective efficacy of one and two doses of the studied VAC∆6 vaccine.
Detailed Description
This is a Double-blind, Comparative, Randomized, Placebo-controlled Study on Immunogenicity, Reactogenicity and Safety of Live Cell-Based Vaccine Against Smallpox and Other Orthopoxvirus Infections (VAC∆6 Vaccine) Based on Vaccinia Virus in 18-60-year-old Volunteers. The study included 334 healthy volunteers of both sexes aged 18-60 years who met the inclusion criteria and had no exclusion criteria. The study was carried out in two stages: The first stage is an open comparative study of the safety, reactogenicity, immunological activity and protective efficacy of VAC∆6 vaccine in parallel groups of 30 volunteers aged 18 to 60 who met the inclusion criteria. Volunteers were divided into two groups: * Group 1: 15 volunteers who received a single intradermal VAC∆6 dose of 1x10⁷ PFU. Live smallpox vaccine was administered by scarification 2 months after the vaccination. * Group 2: 15 volunteers who received two intradermal VAC∆6 doses of 1x10⁶ PFU (given 28 days apart). Live smallpox vaccine was administered by scarification one month after the full vaccination series. The second stage is a Double-blind, Comparative, Randomized, Placebo-controlled study on Immunogenicity, Reactogenicity, and Safety of the VAC∆6 Vaccine in Parallel Groups. Randomization was carried out using the envelope method. The sealed opaque envelopes included in the Investigator's File were distributed to the clinical sites in the required quantity prior to the start of the study. Substances were submitted for testing in encrypted form. The encryption technique was chosen and implemented by the sponsor - FBRI SRC VB "Vector", Rospotrebnadzor. Decryption was carried out after study report submission to the Federal Budgetary Research Institution, State Research Center of Virology and Biotechnology "Vector", Rospotrebnadzor. A total of 304 volunteers aged 18-60 took part in the second stage of the clinical study, of which 158 were men and 146 were women, who met the inclusion criteria and had no exclusion criteria. The volunteers were assigned to study sites as follows: 1. FGBUZ MSCH-163, FMBA Russia - 272 volunteers randomized into four groups: * Group 3: 76 volunteers who received two intradermal VAC∆6 doses of 10⁶ PFU/0.2 ml (given 28 days apart); * Group 4: 76 volunteers who received two intradermal placebo doses of 0.2 ml (given 28 days apart); * Group 5: 60 volunteers who received a single intradermal VAC∆6 dose of 10⁷ PFU/0.2 ml; * Group 6: 60 volunteers who received a single intradermal placebo dose of 0.2 ml. 2. State Budgetary Health Institution of the Novosibirsk Region "Municipal Infectious Disease Clinical Hospital No. 1" - 32 volunteers randomized into two groups: * Group 7: 16 volunteers who received a single intradermal VAC∆6 dose of 10⁷ PFU/0.2 ml; * Group 8: 16 volunteers who received a single intradermal placebo dose of 0.2 ml. * Before applying for a state license to the Ministry of the Russian Federation on May 4, 2022, the VACΔ6 vaccine was renamed to OrthopoxVac.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Signed and dated informed consent of a volunteer to participate in a clinical trial obtained prior to any of the study procedures.
- •A verified diagnosis of "healthy" according to standard clinical, laboratory and instrumental methods of examination.
- •Age from 18 to 60 inclusive.
- •Body mass index from 18.5 to 30 kg/m
- •Ability to attend all scheduled visits and all scheduled procedures and examinations.
- •Consent of volunteers to use effective methods of contraception throughout the study, including the period of observation for possible post-vaccination reactions.
Exclusion Criteria
- •Hypersensitivity to any component of the product, allergy to vaccine components.
- •Pregnancy or breastfeeding.
- •The military.
- •Persons in custody in detention facilities and those serving sentences in correctional facilities.
- •Children under
- •Acute infectious or non-infectious diseases, exacerbation of chronic diseases less than 4 weeks prior to the study.
- •Tuberculosis (pulmonary and extrapulmonary).
- •Skin diseases: a) common dermatoses (pemphigus, psoriasis, eczema, atopic dermatitis), including the history of dermatoses; other acute and chronic diseases or impaired skin cover (burns, impetigo, herpes, herpes zoster/chicken pox, pustular diseases).
- •Immunosuppressive conditions: congenital or acquired immunodeficiency syndrome (including HIV infection), leukemia, malignant neoplasms, organ transplantation, cellular and humoral immunodeficiencies.
- •Immunosuppressive therapy: treatment with antimetabolites, high doses of corticosteroids for 14 days or more, radio and x-ray therapy, etc.
Outcomes
Primary Outcomes
Changes in the percentage of vaccinees with a titer of virus-neutralizing antibodies to vaccinia virus ≥1:40, at specified time intervals.
Time Frame: Group 1: at days 1, 30, 60, 89. Groups 2, 3, 4: at days 1, 28, 57, 87, 117. Groups 5, 6, 7, 8: at days 1, 30, 60, 90.
On control days, the percentage of the vaccinees with a titer of virus-neutralizing antibodies to vaccinia virus ≥1:40 is recorded in the neutralization test in embryonated chicken eggs. Value changes of this indicator between time points are assessed.
Secondary Outcomes
- Change in antibody titers.(Group 1: at days 0, 1, 30, 60, 89. Groups 2, 3, 4: at days 0, 1, 28, 57, 87, 117. Groups 5, 6, 7, 8: at days 0, 1, 30, 60, 90.)
- Determination of the lymphocyte migration index (MI)(Group 1: at days 30, 89. Groups 2, 3, 4: at days 1, 28, 57, 117. Groups 5, 6, 7, 8: at days 1, 30, 90.)
- Determination of the integral indicator of the effector functions (IEF)(Group 1: at days 30, 89. Groups 2, 3, 4: at days 1, 28, 57, 117. Groups 5, 6, 7, 8: at days 1, 30, 90.)
- Recording of the percentage of the vaccinated with various degrees of manifestation of systemic and local reactions.(Group 1: at days 1-14, 21, 30, 60-74, 80, 89. Group 2: at days 1-14, 21, 28-41, 48, 57, 87-100, 107, 116. Groups 3, 4: at days 1-14, 21, 28-41, 48, 57, 87, 117. Groups 5, 6, 7, 8: at days 1-14, 21, 30.)
- Recording the number of local reactions.(Group 1: at days 1-14, 21, 30, 60-74, 80, 89. Group 2: at days 1-14, 21, 28-41, 48, 57, 87-100, 107, 116. Groups 3, 4: at days 1-14, 21, 28-41, 48, 57, 87, 117. Groups 5, 6, 7, 8: at days 1-14, 21, 30.)
- Determination of the lymphocyte migration inhibition index (MII)(Group 1: at days 30, 89. Groups 2, 3, 4: at days 1, 28, 57, 117. Groups 5, 6, 7, 8: at days 1, 30, 90.)
- Recording the number of systemic reactions.(Group 1: at days 1-14, 21, 30, 60-74, 80, 89. Group 2: at days 1-14, 21, 28-41, 48, 57, 87-100, 107, 116. Groups 3, 4: at days 1-14, 21, 28-41, 48, 57, 87, 117. Groups 5, 6, 7, 8: at days 1-14, 21, 30.)