Study on Immunogenicity, Reactogenicity and Safety of the VACΔ6 Vaccine in Volunteers Aged 18-60 Years
Condition: Smallpox; Monkeypox; Cowpox; Vaccinia Virus Infection
MeSH terms: Infections; Vaccinia; Smallpox; Monkeypox
Study type: Interventional
Phase: Phase 2/Phase 3

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:

        1. To study the immunological activity of a single VAC∆6 vaccine dose of 1x10⁷
           plaque-forming units (PFU).

        2. To study the immunological activity of two VAC∆6 vaccine doses (given 28 days apart) of
           1x10⁶ PFU.

        3. 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).

        4. 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).

        5. To identify VAC∆6 vaccine-associated adverse events.

        6. Study cell-mediated immunity induced by different VAC∆6 vaccination schedules.

        7. Determine the presence of the virus in specific skin formations (crusts, pustules),
           saliva, blood and urine.

        8. 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.
    

Intervention name(s): VAC∆6 vaccine (10⁷ PFU); VAC∆6 vaccine (10⁶ PFU); Live Smallpox Vaccine; Placebo (Sodium chloride bufus, 0.9%)
Intervention type(s): Biological; Biological; Biological; Other
Intervention description(s): Live cell-based vaccine against smallpox and other orthopoxvirus infections (VAC∆6 vaccine) based on vaccinia virus (manufactured by FBRI SRC VB "Vector", Rospotrebnadzor).
Batch: 08-10.19 (expiry date: 13.10.2021). Dosage: single intradermal dose of 10⁷ PFU/0.2 ml of vaccinia virus.; Live cell-based vaccine against smallpox and other orthopoxvirus infections (VAC∆6 vaccine) based on vaccinia virus (manufactured by FBRI SRC VB "Vector", Rospotrebnadzor).
Batch: 08-10.19 (expiry date: 13.10.2021). Dosage: two intradermal doses of 10⁶ PFU/0.2 ml of vaccinia virus (given 28 days apart).; Live smallpox vaccine (Smallpox vaccine) (manufactured by the Federal State Unitary Enterprise NPO Microgen of the Ministry of Health of Russia).
Batch No. Т30 (expiry date: March, 2021). Dosage: Single 1x10⁶ PFU dose administered by multiple-pricking technique on the 30th/60th day after full series of vaccination with VAC∆6.; Sodium chloride bufus, a 0.9% solvent for the preparation of a dosage form for injections (manufactured by JSC Pharmaceutical manufacturing company "Obnovlenie", Russia).
Batch: 391219 (expiry date: January, 2025).
Intervention MeSH terms: Vaccines
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This was a clinical study of VAC∆6 vaccine designed to induce specific immunity to human-pathogenic orthopoxviruses (VARV, MPXV, CPXV, VACV)
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: VAC∆6 vaccine; Оrthopoxviruses; Smallpox; Сlinical study