Study on Immunogenicity, Reactogenicity and Safety of the VACΔ6 Vaccine in Volunteers Aged 18-60 Years

NCT05846243 | Completed Phase 2

• 1 other identifier: VAC∆6-01/20
• Study Type: interventional
• Target: 334
• Locations: 1 country
• Sites: 2

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:

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

Conditions

Smallpox; Monkeypox; Cowpox; Vaccinia Virus Infection

Keywords

VAC∆6 vaccine; Оrthopoxviruses; Smallpox; Сlinical study

Outcome Measures

Primary Outcomes (1)

• Changes in the percentage of vaccinees with a titer of virus-neutralizing antibodies to vaccinia virus ≥1:40, at specified time intervals.

  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.

  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.

Secondary Outcomes (7)

• 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 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.

• 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 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.

Other Outcomes (41)

• Body temperature monitoring at specified time intervals.

  Group 1: at days 0-14, 21, 30, 60-74, 80, 89. Group 2: at days 0-14, 21, 28-41, 48, 57, 87-100, 107, 116. Groups 3, 4: at days 0-14, 21, 28-41, 48, 57, 87, 117. Groups 5, 6, 7, 8: at days 1-14, 21, 30.

• Arterial blood pressure monitoring at specified time intervals.

  Group 1: at days 0-14, 21, 30, 60-74, 80, 89. Group 2: at days 0-14, 21, 28-41, 48, 57, 87-100, 107, 116. Groups 3, 4: at days 0-14, 21, 28-41, 48, 57, 87, 117. Groups 5, 6, 7, 8: at days 1-14, 21, 30.

• Heart rate monitoring at specified time intervals.

  Group 1: at days 0-14, 21, 30, 60-74, 80, 89. Group 2: at days 0-14, 21, 28-41, 48, 57, 87-100, 107, 116. Groups 3, 4: at days 0-14, 21, 28-41, 48, 57, 87, 117. Groups 5, 6, 7, 8: at days 1-14, 21, 30.

Study Arms (8)

Group 1 (The first stage): VAC∆6 (10⁷ PFU), Live Smallpox Vaccine (2 months after the vaccination)

EXPERIMENTAL

15 volunteers aged 18 to 60 who met the inclusion criteria and who received a single intradermal VAC∆6 dose of 1x10⁷ PFU/0.2ml. Live smallpox vaccine was administered by scarification 2 months after the vaccination. (The first stage is an open comparative study of the safety, reactogenicity, immunological activity and protective efficacy of VAC∆6 vaccine in two parallel groups).

Biological: VAC∆6 vaccine (10⁷ PFU); Biological: Live Smallpox Vaccine

Group 2 (The first stage): VAC∆6 (10⁶ PFU), Live Smallpox Vaccine (1 month after the vaccination)

EXPERIMENTAL

15 volunteers aged 18 to 60 who met the inclusion criteria and who received two intradermal VAC∆6 doses of 10⁶ PFU/0.2ml (given 28 days apart). Live smallpox vaccine was administered by scarification one month after the full vaccination series. (The first stage is an open comparative study of the safety, reactogenicity, immunological activity and protective efficacy of VAC∆6 vaccine in two parallel groups).

Biological: VAC∆6 vaccine (10⁶ PFU); Biological: Live Smallpox Vaccine

Group 3 (The second stage): two intradermal VAC∆6 (10⁶ PFU/0.2 ml) given 28 days apart.

EXPERIMENTAL

76 volunteers aged 18 to 60 who met the inclusion criteria and who received two intradermal VAC∆6 doses of 10⁶ PFU/0.2 ml (given 28 days apart). (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).

Biological: VAC∆6 vaccine (10⁶ PFU)

Group 4 (The second stage): two intradermal placebo doses of 0.2 ml (given 28 days apart).

PLACEBO COMPARATOR

76 volunteers aged 18 to 60 who met the inclusion criteria and who received two intradermal placebo doses of 0.2 ml (given 28 days apart). (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).

Other: Placebo (Sodium chloride bufus, 0.9%)

Group 5 (The second stage) in the FGBUZ MSCH-163: a single intradermal VAC∆6 (10⁷ PFU/0.2 ml).

EXPERIMENTAL

60 volunteers aged 18 to 60 who met the inclusion criteria and who received a single intradermal VAC∆6 dose of 10⁷ PFU/0.2 ml. (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).

Biological: VAC∆6 vaccine (10⁷ PFU)

Group 6 (The second stage) in the FGBUZ MSCH-163: a single intradermal placebo dose of 0.2 ml.

PLACEBO COMPARATOR

60 volunteers aged 18 to 60 who met the inclusion criteria and who received a single intradermal placebo dose of 0.2 ml. (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).

Other: Placebo (Sodium chloride bufus, 0.9%)

Group 7 (The second stage) in the Hospital No. 1: a single intradermal VAC∆6 (10⁷ PFU/0.2 ml).

EXPERIMENTAL

16 volunteers aged 18 to 60 who met the inclusion criteria and who received a single intradermal VAC∆6 dose of 10⁷ PFU/0.2 ml. (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).

Biological: VAC∆6 vaccine (10⁷ PFU)

Group 8 (The second stage): in the Hospital No. 1: a single intradermal placebo dose of 0.2 ml.

PLACEBO COMPARATOR

16 volunteers aged 18 to 60 who met the inclusion criteria and who received a single intradermal placebo dose of 0.2 ml. (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).

Other: Placebo (Sodium chloride bufus, 0.9%)

Interventions

VAC∆6 vaccine (10⁷ PFU) BIOLOGICAL

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.

Group 1 (The first stage): VAC∆6 (10⁷ PFU), Live Smallpox Vaccine (2 months after the vaccination); Group 5 (The second stage) in the FGBUZ MSCH-163: a single intradermal VAC∆6 (10⁷ PFU/0.2 ml).; Group 7 (The second stage) in the Hospital No. 1: a single intradermal VAC∆6 (10⁷ PFU/0.2 ml).

VAC∆6 vaccine (10⁶ PFU) BIOLOGICAL

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).

Group 2 (The first stage): VAC∆6 (10⁶ PFU), Live Smallpox Vaccine (1 month after the vaccination); Group 3 (The second stage): two intradermal VAC∆6 (10⁶ PFU/0.2 ml) given 28 days apart.

Live Smallpox Vaccine BIOLOGICAL

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.

Group 1 (The first stage): VAC∆6 (10⁷ PFU), Live Smallpox Vaccine (2 months after the vaccination); Group 2 (The first stage): VAC∆6 (10⁶ PFU), Live Smallpox Vaccine (1 month after the vaccination)

Placebo (Sodium chloride bufus, 0.9%) OTHER

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).

Group 4 (The second stage): two intradermal placebo doses of 0.2 ml (given 28 days apart).; Group 6 (The second stage) in the FGBUZ MSCH-163: a single intradermal placebo dose of 0.2 ml.; Group 8 (The second stage): in the Hospital No. 1: a single intradermal placebo dose of 0.2 ml.

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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/m3.
• 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.

You may not qualify if:

• 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 18.
• 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.
• Regular medication intake less than 2 weeks before the start of the study.
• Taking immunoglobulin drugs or blood products within the last 3 months before the start of the study.
• Donation (450 ml of blood or plasma or more) less than 2 months before the start of the study.
• Cardiovascular diseases: decompensated heart defects, subacute bacterial endocarditis, myocarditis, pericarditis, stage 2-3 hypertension, angina pectoris, myocardial infarction; other forms of pathology: stage 1 hypertension, well-controlled heart defects, angina pectoris (mild forms).
• Diseases of the kidneys and urinary tract: diffuse glomerulonephritis, congenital nephropathy, chronic renal failure, pyelonephritis, toxic nephropathy (transient).

Sponsors & Collaborators

• Federal Budgetary Research Institution State Research Center of Virology and Biotechnology "Vector": lead

Study Sites (2)

Federal State Budgetary Institution of Healthcare "Medical and Sanitary Unit No. 163 of the Federal Medical and Biological Agency" (FGBUZ MSCH-163, FMBA of Russia)

Kol'tsovo, Novosibirsk Oblast, 630559, Russia

Location

State Budgetary Health Institution of the Novosibirsk Region "Municipal Infectious Disease Clinical Hospital No. 1"

Novosibirsk, 630099, Russia

Location

Related Publications (11)

• Yakubitskiy SN, Kolosova IV, Maksyutov RA, Shchelkunov SN. Attenuation of Vaccinia Virus. Acta Naturae. 2015 Oct-Dec;7(4):113-21.

  PMID: 26798498 BACKGROUND

• Maksyutov RA, Yakubitskyi SN, Kolosova IV, Shchelkunov SN. Comparing New-Generation Candidate Vaccines against Human Orthopoxvirus Infections. Acta Naturae. 2017 Apr-Jun;9(2):88-93.

  PMID: 28740731 BACKGROUND

• Olson VA, Shchelkunov SN. Are We Prepared in Case of a Possible Smallpox-Like Disease Emergence? Viruses. 2017 Aug 27;9(9):242. doi: 10.3390/v9090242.

  PMID: 32962316 BACKGROUND

• Shchelkunova GA, Shchelkunov SN. Smallpox, Monkeypox and Other Human Orthopoxvirus Infections. Viruses. 2022 Dec 29;15(1):103. doi: 10.3390/v15010103.

  PMID: 36680142 BACKGROUND

• Shchelkunova GA, Shchelkunov SN. 40 Years without Smallpox. Acta Naturae. 2017 Oct-Dec;9(4):4-12.

  PMID: 29340212 BACKGROUND

• Shchelkunov SN, Shchelkunova GA. Genes that Control Vaccinia Virus Immunogenicity. Acta Naturae. 2020 Jan-Mar;12(1):33-41. doi: 10.32607/actanaturae.10935.

  PMID: 32477596 BACKGROUND

• Shchelkunov SN, Shchelkunova GA. [We should be prepared to smallpox re-emergence.]. Vopr Virusol. 2019;64(5):206-214. doi: 10.36233/0507-4088-2019-64-5-206-214. Russian.

  PMID: 32167685 BACKGROUND

• Maksyutov RA, Yakubitskiy SN, Kolosova IV, Tregubchak TV, Shvalov AN, Gavrilova EV, Shchelkunov SN. Genome stability of the vaccine strain VACDelta6. Vavilovskii Zhurnal Genet Selektsii. 2022 Jul;26(4):394-401. doi: 10.18699/VJGB-22-48.

  PMID: 35903306 BACKGROUND

• Marennikova S.S., Shchelkunov S.N. Orthopoxviruses pathogenic for humans (monograph) // KMK Scientific Press Ltd., M. - 1998, - 386 p (in Russian).

  BACKGROUND

• Kolosova I.V., Babkina I.N., Yakubitsky S.N., Maksyutov R.A., Safronov P.F., Shchelkunov S.N. Recombinant strain L-IVP 1421ABJCN of vaccinia virus with deleted virulence genes A56R, B8R, J2R, C3L, N1L to obtain a live cell-based attenuated vaccine against smallpox and other orthopoxviruses pathogenic to humans // RF Patent No. 2588388, priority 20.04.2015 (in Russian).

  BACKGROUND

• Yakubitsky S.N., Kolosova I.V., Maksyutov R.A., Shchelkunov S.N. Recombinant strain VACΔ6 of vaccinia virus with deleted virulence genes C3L, N1L, J2R, A35R, A56R, B8R for obtaining a live cell-based attenuated vaccine against smallpox and other human orthopoxvirus infections // RF Patent No. 2621868, priority 24.06.2016 (in Russian).

  BACKGROUND

MeSH Terms

Conditions

Smallpox; Mpox, Monkeypox; Cowpox

Condition Hierarchy (Ancestors)

Poxviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Primate Diseases; Animal Diseases; Rodent Diseases

Study Officials

• Vladimir I. Kuzubov, PhD

  Medical and Sanitary Unit No. 163 (FGBUZ MSCH-163, FMBA Russia) (Novosibirsk)

  PRINCIPAL INVESTIGATOR

• Irina V Krasil'nikova, PhD

  Municipal Infectious Disease Clinical Hospital No. 1 (Novosibirsk)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double-blind Study
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: This was a clinical study of VAC∆6 vaccine designed to induce specific immunity to human-pathogenic orthopoxviruses (VARV, MPXV, CPXV, VACV)

Study Record Dates

• First Submitted: March 23, 2023
• First Posted: May 6, 2023
• Study Start: October 1, 2021
• Primary Completion: December 31, 2021
• Study Completion: April 1, 2022
• Last Updated: May 6, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

RU (2)