Safety and Tolerability Study of the VAC∆6 Vaccine in Volunteers Aged 18-40 Years

NCT05762523 | Completed Phase 1

• 1 other identifier: VAC∆6-01/18
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of the clinical study is to study the safety and tolerability of the live cell-based vaccine against smallpox and other orthopoxvirus infections (VAC∆6 vaccine) based on vaccinia virus, in intracutaneous administration. The research tasks are to:

• evaluate the safety of various schemes for the use of the VAC∆6 vaccine using a set of clinical and laboratory-instrumental methods (thermometry, blood pressure registration, auscultation of the heart and lungs, electrocardiography (ECG), complete blood count and common urine test, biochemical, immunological, and virological studies);
• evaluate the reactogenicity of various schemes for the use of the VAC∆6 vaccine (taking into account the number of local and systemic reactions, the percentage of those vaccinated with various degrees of manifestation of systemic and local reactions);
• evaluate the possibility of virus shedding into the environment by volunteers;
• evaluate the immunological efficacy of various vaccine administration schemes;
• identify the development of undesirable reactions to the administration of the vaccine;
• evaluate the cellular immune response to the introduction of various schemes for the use of the vaccine;
• evaluate preliminary efficacy data in order to select an optimal scheme for the administration of the vaccine to make a decision on conducting Phase II clinical trials in an extended group of volunteers.

Conditions

Smallpox; Monkeypox; Cowpox; Vaccinia Virus Infection

Keywords

VAC∆6 vaccine; Smallpox; Оrthopoxviruses; Сlinical study

Outcome Measures

Primary Outcomes (2)

• 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.

  Groups 1, 2, 3: at days 0, 21, 30, 60, 90, 180. Group 4: at days 0, 5, 12, 21, 28, 37, 67, 97, 187.

• Recording the number of local reactions.

  On control days, the sum of local reactions is recorded: formation of inoculation elements (redness, swelling and papulo-nodules, pustules, vesicles, erythema, induration). Value changes of this indicator between time points are assessed. Evaluation criteria for local reactions: 1. The intensity or severity of adverse reactions should be assessed on a 4-point scale: 0 - none (no symptoms); 1 - mild (presence of mild symptoms); 2 - medium (symptoms that noticeably impair normal daily activities); 3 - severe (symptoms that interfere with normal daily activities). 2. The severity of local reactions was assessed according to the following criteria: * Hyperemia \< 50.0 mm (⌀) or an infiltrate \< 25.0 mm (⌀) - weak; * Hyperemia ≤ 50.0 mm (⌀) or an infiltrate 26.0-50.0 mm (⌀) - medium; * Infiltrate \> 50.0 mm (⌀) - strong.

  Groups 1, 2: at days 0 - 14, 21. Group 3: at days 0 - 14, 21, 28 - 42, 49. Group 4: at days 0 - 22, 29.

Secondary Outcomes (5)

• Changes in the activity of delayed-type hypersensitivity (DTH) effectors to vaccinia virus at specified time intervals.

  Groups 1, 2: at days 1, 30, 90. Groups 3, 4: at days 1, 30, 60, 90.

• Changes in the content of Class A, M, G, and E immunoglobulins.

  Groups 1, 2, 3: at days 0, 5, 14, 21, 30, 60, 90, 180. Group 4: at days 0, 5, 12, 21, 28, 37, 67, 97, 187.

• Changes in the content of T cells and their subpopulations: cluster of differentiation 3 (CD3+), cluster of differentiation 4 (CD4+), cluster of differentiation 8 (CD8+), CD4+/CD8+.

  Groups 1, 2, 3: at days 0, 5, 14, 21, 30, 60, 90, 180. Group 4: at days 0, 5, 12, 21, 28, 37, 67, 97, 187.

• Recording the number of systemic reactions.

  Groups 1, 2: at days 0 - 14, 21. Group 3: at days 0 - 14, 21, 28 - 42, 49. Group 4: at days 0 - 22, 29.

• Recording of the percentage of the vaccinated with various degrees of manifestation of systemic and local reactions.

  Groups 1, 2: at days 0 - 14, 21. Group 3: at days 0 - 14, 21, 28 - 42, 49. Group 4: at days 0 - 22, 29.

Other Outcomes (38)

• Body temperature monitoring at specified time intervals.

  Groups 1, 2, 3: at days 0, 5, 14, 21, 30, 60, 90, 180. Group 4: at days 0, 5, 12, 21, 28, 37, 67, 97, 187.

• Arterial blood pressure monitoring at specified time intervals.

  roups 1, 2, 3: at days 0, 5, 14, 21, 30, 60, 90, 180. Group 4: at days 0, 5, 12, 21, 28, 37, 67, 97, 187.

• Heart rate monitoring at specified time intervals.

  Groups 1, 2, 3: days 0, 5, 14, 21, 30, 60, 90, 180. Group 4: days 0, 5, 12, 21, 28, 37, 67, 97, 187.

Study Arms (4)

Group 1 "VAC∆6: оnce at a dose of 10⁶ PFU (plaque-forming units)"

EXPERIMENTAL

15 healthy volunteers of both sexes aged 18-40 years who had not been vaccinated against smallpox, had no vaccine marks and anti-smallpox virus neutralizing antibodies in their sera as well as those who met the inclusion criteria and did not have any exclusion criteria

Biological: VAC∆6 vaccine - оnce at a dose of 10⁶ PFU

Group 2 "VAC∆6: once at a dose of 10⁷ PFU"

EXPERIMENTAL

15 healthy volunteers of both sexes aged 18-40 years who had not been vaccinated against smallpox, had no vaccine marks and anti-smallpox virus neutralizing antibodies in their sera as well as those who met the inclusion criteria and did not have any exclusion criteria

Biological: VAC∆6 vaccine - once at a dose of 10⁷ PFU

Group 3 "VAC∆6: twice at a dose of 10⁶ PFU"

EXPERIMENTAL

15 healthy volunteers of both sexes aged 18-40 years who had not been vaccinated against smallpox, had no vaccine marks and anti-smallpox virus neutralizing antibodies in their sera as well as those who met the inclusion criteria and did not have any exclusion criteria

Biological: VAC∆6 vaccine - twice at a dose of 10⁶ PFU

Group 4 "OspaVir® + live smallpox vaccine"

EXPERIMENTAL

15 healthy volunteers of both sexes aged 18-40 years who had not been vaccinated against smallpox, had no vaccine marks and anti-smallpox virus neutralizing antibodies in their sera as well as those who met the inclusion criteria and did not have any exclusion criteria

Biological: Live smallpox vaccine (Smallpox vaccine) + The OspaVir® inactivated smallpox vaccine

Interventions

VAC∆6 vaccine - оnce at a dose of 10⁶ PFU BIOLOGICAL

15 volunteers vaccinated once intradermally at a dose of 10⁶ PFU (0.2 ml) of the VAC∆6 vaccine in the outer surface of the shoulder 8-10 cm below the shoulder joint

Group 1 "VAC∆6: оnce at a dose of 10⁶ PFU (plaque-forming units)"

VAC∆6 vaccine - once at a dose of 10⁷ PFU BIOLOGICAL

15 volunteers vaccinated once intradermally at a dose of 10⁷ PFU (0.2 ml) of the VAC∆6 vaccine in the outer surface of the shoulder 8-10 cm below the shoulder joint

Group 2 "VAC∆6: once at a dose of 10⁷ PFU"

VAC∆6 vaccine - twice at a dose of 10⁶ PFU BIOLOGICAL

15 volunteers vaccinated twice spaced 28 days apart, intradermally at a dose of 10⁶ PFU (0.2 ml) of the VAC∆6 vaccine in the outer surface of the shoulder 8-10 cm below the shoulder joint

Group 3 "VAC∆6: twice at a dose of 10⁶ PFU"

Live smallpox vaccine (Smallpox vaccine) + The OspaVir® inactivated smallpox vaccine BIOLOGICAL

15 volunteers vaccinated by the two-step vaccination method: Step 1 - the first vaccination once subcutaneously with 1 dose (0.5 ml) of the inactivated smallpox vaccine OspaVir® in the area of the left shoulder 8-10 cm below the shoulder joint; Step 2 - the second vaccination once by the method of multiple puncture into the outer surface of the shoulder 8-10 cm below the shoulder joint with a live smallpox vaccine at a dose of 1x 106 PFU 7 days following the first vaccination with OspaVir®.

Group 4 "OspaVir® + live smallpox vaccine"

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Consent to participate in the study after written informing.
• Healthy volunteers (men and women) aged 18 to 40:
• absence of somatic or infectious diseases during the last 6 months;
• body weight of volunteers should not go beyond 20% of the ideal body weight for a given sex, age, and height;
• absence during the last 6 months of antiviral therapy, the use of steroids (except for the local use of steroids in the form of ointments, eye drops, sprays or inhalations), immunomodulatory dugs;
• persons not infected with HIV, viral hepatitis B and C, lues;
• clinical and laboratory parameters within the range as follows: leukocytes: from 4,000 to 10,000 cells/mm³; platelets: 180,000 to 320,000 per mm³.

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 the age of 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 those in the past; 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.
• Cardiovascular diseases: decompensated heart defects, subacute bacterial endocarditis, myocarditis, pericarditis, hypertension of II-III degrees, angina pectoris, myocardial infarction; other forms of pathology: hypertension of the 1st degree, 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).
• Diseases of the digestive system: cirrhosis of the liver, chronic hepatitis, hepatocerebral dystrophy, acute and chronic pancreatitis, diseases of the biliary tract, gastric ulcer and duodenal ulcer, ulcerative colitis.
• Diseases of the endocrine system: diabetes mellitus, severe forms of thyrotoxicosis and adrenal insufficiency or dysfunction, thymomegaly, congenital enzymopathy.
• Systemic connective tissue diseases: systemic lupus erythematosus, discoid lupus, rheumatism, rheumatoid arthritis, systemic vasculitis, systemic scleroderma.

Sponsors & Collaborators

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

Study Sites (1)

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

Novosibirsk, Koltsovo, Novosibirsk Region, 630559, 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

• Yakubitskyi SN, Kolosova IV, Maksyutov RA, Shchelkunov SN. Highly immunogenic variant of attenuated vaccinia virus. Dokl Biochem Biophys. 2016;466:35-8. doi: 10.1134/S1607672916010105. Epub 2016 Mar 31.

  PMID: 27025484 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. 40 Years without Smallpox. Acta Naturae. 2017 Oct-Dec;9(4):4-12.

  PMID: 29340212 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

• 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

• Marennikova SS, Shchelkunov SN. Orthopoxviruses pathogenic for humans (monograph). KMK Scientific Press Ltd.1998; 386 p. (in Russian).

  BACKGROUND

• Kolosova IV, Babkina IN, Yakubitsky SN, Maksyutov RA, Safronov PF, Shchelkunov SN. 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 SN, Kolosova IV, Maksyutov RA, Shchelkunov SN. 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

Interventions

Smallpox Vaccine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Vladimir I. Kuzubov, PhD

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: This study is an open-label, controlled, parallel-group clinical trial.

Study Record Dates

• First Submitted: January 23, 2023
• First Posted: March 9, 2023
• Study Start: May 18, 2019
• Primary Completion: July 22, 2019
• Study Completion: January 27, 2020
• Last Updated: March 9, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

RU (1)