SmallpoxPhase 1NCT05762523

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

A Phase 1 study testing VAC∆6 vaccine - оnce at a dose of 10⁶ PFU, VAC∆6 vaccine - once at a dose of 10⁷ PFU and VAC∆6 vaccine - twice at a dose of 10⁶ PFU in people with Smallpox and Monkeypox, run by Federal Budgetary Research Institution State Research Center of Virology and Biotechnology "Vector" at 1 site in Russia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 40 yearsHealthy volunteers can take part
Conditions the study is for: Smallpox, Monkeypox, Cowpox
What is being tested?: VAC∆6 vaccine - оnce at a dose of 10⁶ PFU, VAC∆6 vaccine - once at a dose of 10⁷ PFU and VAC∆6 vaccine - twice at a dose of 10⁶ PFU
Type of treatment: Vaccines, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 60 participants
Where: 1 siteRussia
Study dates: 18 May 2019to 27 Jan 2020
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 40 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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.

Who cannot join

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.

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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.
Blood diseases: leukemia, Hodgkin's disease, aplastic anemia, hemophilia, Werlhof's disease; hemolytic conditions; deficiency anemia.
Allergic diseases: bronchial asthma; asthmatic bronchitis, asthmatic syndrome (associated with a respiratory infection); severe anaphylactic reactions (shock, angioedema of the larynx, etc.) to a variety of food, drug and other allergens; allergic reactions to individual allergens (various rashes, clinical disorders, etc.).
Diseases of the ear, throat, nose: chronic tonsillitis and adenoiditis requiring surgical treatment; chronic otitis.
Surgery within the previous 2 months.
Simultaneous participation in other clinical trials.
Persons with alcohol, drug or drug addiction.
The presence of mental illness and neurasthenia.
Previous treatment with human immunoglobulin preparations, if less than 6 months have passed since the treatment.
Failure to meet inclusion criteria.
Vaccination with any vaccine less than 2 months prior to study entry.
Premenopausal women (last menstrual period ≤ 1 year prior to signing the informed consent) who are not surgically sterile.
Women who have reproductive potential or do not use or plan to use approved birth control products throughout the study nor they agree to a urine pregnancy test while participating in the study. Acceptable birth control methods include extrauterine devices, oral, implanted, or injectable contraceptives.
Nervous and mental diseases: injuries of the central nervous system (CNS) with residual effects, encephalitis and encephalomyelitis (including post-vaccination), meningitis, polyradiculoneuritis (including those in the past), epilepsy, decompensates or subcompensated hydrocephalus, demyelinating and degenerative lesions of the nervous system (muscle degeneration, etc.), stroke; compensated hydrocephalus, Down's disease, Little's disease, CNS trauma without residual effects, history of febrile convulsions, mental illness.
Positive analysis for HIV, viral hepatitis B and C, lues.
Concomitant diseases that, in the opinion of the investigator, may interfere with the evaluation of the objectives of the study.
Serious post-vaccination reactions/complications associated with any previous vaccination.

Trial locations and contacts

1 site in 1 country.

Russia1 site

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

Other trials in Russia

About this study

Official title: An Open-label Controlled Study of the Safety and Tolerability of the Live Cell-based Vaccine Against Smallpox and Other Orthopoxvirus Infections (VAC∆6 Vaccine) Based on Vaccinia Virus, in Volunteers Aged 18-40 Years

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.

Read the detailed description

This study is an open-label, controlled, parallel-group clinical trial. The study included 60 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.

Distribution of volunteers by groups:

Group 1: 15 volunteers vaccinated once intradermally at a dose of 10⁶ plaque-forming units (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: 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 3: 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 4: 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®.

Since the product "Live cell-based vaccine against smallpox and other orthopoxvirus infections (VAC∆6 vaccine) based on vaccinia virus" was used for the first time for human vaccination, the vaccination of volunteers was started at a low dose, i.e. 1x10⁶ PFU.

The first five volunteers included in Group 1 were vaccinated intradermally at a dose of 1x10⁶ PFU. The volunteers were monitored daily; 14 days after vaccination, in the absence of side effects and after the results were agreed upon, vaccination was performed for the remaining 10 Group 1 volunteers and the first 5 volunteers of Group 2 who were vaccinated at a dose of 1x10⁷ PFU. After 14 days, in the absence of adverse effects (AEs) or serious adverse effects (SAEs), the rest of the volunteers included in Group 2 were vaccinated.

After receiving the results indicating the absence of AEs or SAEs in the volunteers vaccinated once with the VAC∆6 vaccine at a dose of 1x10⁶ PFU, the first vaccination of Group 3 volunteers was performed, the dose of the vaccine was 1x10⁶ PFU, and after 28 days - the second vaccination was performed.

Group 4 was vaccinated with reference products: live smallpox vaccine (smallpox vaccine) and the OspaVir® vaccine, an inactivated smallpox vaccine.

Vaccination was performed in two steps:

the first step: subcutaneous administration of the inactivated smallpox vaccine OspaVir®;
the second step: skin inoculation with a live smallpox vaccine.

Conditions: Smallpox, Monkeypox, Cowpox, Vaccinia Virus Infection
Being tested: VAC∆6 vaccine - оnce at a dose of 10⁶ PFU, VAC∆6 vaccine - once at a dose of 10⁷ PFU, VAC∆6 vaccine - twice at a dose of 10⁶ PFU, Live smallpox vaccine (Smallpox vaccine) + The OspaVir® inactivated smallpox vaccine
Keywords: VAC∆6 vaccine, Smallpox, Оrthopoxviruses, Сlinical study
Medical subject headings: Smallpox, Mpox, Monkeypox, Cowpox

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

VAC∆6 vaccine - оnce at a dose of 10⁶ PFUBiological
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
VAC∆6 vaccine - once at a dose of 10⁷ PFUBiological
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
VAC∆6 vaccine - twice at a dose of 10⁶ PFUBiological
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
Live smallpox vaccine (Smallpox vaccine) + The OspaVir® inactivated smallpox vaccineBiological
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®.

Study groups in NCT05762523
Study group	Role	What they receive
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 Receives: 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 Receives: 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 Receives: 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 Receives: Biological: Live smallpox vaccine (Smallpox vaccine) + The OspaVir® inactivated smallpox vaccine

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
On control days, the changes in the activity of DTH effectors to vaccinia virus are assessed. The assessment of the activity of specific DTH effectors in vitro should be carried out according to the migration index (MI), which characterizes the migration activity of leukocytes; according to the migration inhibition index (MII), which characterizes the intensity of lymphokine production, and according to the integral indicator of the effector functions (IEF). The reaction is considered positive if the difference between the experimental and control values is greater than 20%.
Measured: 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.
On control days, the changes in the content of Class A (in mg/ml), M (in mg/ml), G (in mg/ml), and E (in IU/ml) immunoglobulins is assessed.
Measured: 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+.
On control days, the changes in the content of T cells and their subpopulations is assessed: CD3+ (in % in relation to the total number of lymphocytes), CD4+ (in % in relation to CD3+), CD8+ (in % in relation to CD3+), CD4+/CD8+.
Measured: 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.
Recording the number of systemic reactions (malaise, headache, rise in body temperature, weakness, sweating, sleep and appetite disorders, nausea, vomiting, abdominal pain, etc.). Evaluating criteria for systemic 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 temperature response should be evaluated according to the following categories in °С: 0 (none) ≤ 37 °C; 1 (weak) > 37 °С - ≤ 37.5 °С; 2 (medium) > 37.5 °С - ≤ 38.5 °С; 3 (strong) > 38.5°C.
Measured: 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.
Recording of the percentage of the vaccinated with various degrees of manifestation of systemic and local reactions.
Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

18 May 201927 Jan 2020

First posted9 Mar 2023
Study start18 May 2019
Primary completion22 Jul 2019
Study completion27 Jan 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (11)Papers the sponsor has linked to this study.
Other trials for SmallpoxStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Model description: This study is an open-label, controlled, parallel-group clinical trial.
Masking: None (open label)
Enrolment: 60 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05762523
Sponsor's protocol ID: VAC∆6-01/18
Status last verified: Feb 2023
First submitted: 23 Jan 2023
Last updated: 9 Mar 2023
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

Yakubitskiy SN, Kolosova IV, Maksyutov RA, Shchelkunov SN. Attenuation of Vaccinia Virus. Acta Naturae. 2015 Oct-Dec;7(4):113-21.
PubMed 26798498
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.
PubMed 27025484
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.
PubMed 28740731
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.
PubMed 32962316
Shchelkunova GA, Shchelkunov SN. 40 Years without Smallpox. Acta Naturae. 2017 Oct-Dec;9(4):4-12.
PubMed 29340212
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.
PubMed 32167685
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.
PubMed 35903306
Shchelkunov SN, Shchelkunova GA. Genes that Control Vaccinia Virus Immunogenicity. Acta Naturae. 2020 Jan-Mar;12(1):33-41. doi: 10.32607/actanaturae.10935.
PubMed 32477596
Marennikova SS, Shchelkunov SN. Orthopoxviruses pathogenic for humans (monograph). KMK Scientific Press Ltd.1998; 386 p. (in Russian).
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)
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).

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 9 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-label Controlled Study of the Safety and Tolerability of the Live Cell-based Vaccine Against Smallpox and Other Orthopoxvirus Infections (VAC∆6 Vaccine) Based on Vaccinia Virus, in Volunteers Aged 18-40 Years
ClinicalTrials.gov ID: NCT05762523
Acronym / sponsor ID: VAC∆6-01/18
Conditions: Smallpox, Monkeypox, Cowpox, Vaccinia Virus Infection
Keywords: VAC∆6 vaccine, Smallpox, Оrthopoxviruses, Сlinical study
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 60 participants (actual)
Lead sponsor: Federal Budgetary Research Institution State Research Center of Virology and Biotechnology "Vector"Other government
Study start: 18 May 2019 (actual)
Primary completion: 22 Jul 2019 (actual)
Study completion: 27 Jan 2020 (actual)
First posted: 9 Mar 2023 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Detailed description

Distribution of volunteers by groups:

Group 4 was vaccinated with reference products: live smallpox vaccine (smallpox vaccine) and the OspaVir® vaccine, an inactivated smallpox vaccine.

Vaccination was performed in two steps:

the first step: subcutaneous administration of the inactivated smallpox vaccine OspaVir®;
the second step: skin inoculation with a live smallpox vaccine.

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 4
Model description: This study is an open-label, controlled, parallel-group clinical trial.

Arm	Type	Receives
Group 1 "VAC∆6: оnce at a dose of 10⁶ PFU (plaque-forming units)"	Experimental	Biological: VAC∆6 vaccine - оnce at a dose of 10⁶ PFU15 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
Group 2 "VAC∆6: once at a dose of 10⁷ PFU"	Experimental	Biological: VAC∆6 vaccine - once at a dose of 10⁷ PFU15 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
Group 3 "VAC∆6: twice at a dose of 10⁶ PFU"	Experimental	Biological: VAC∆6 vaccine - twice at a dose of 10⁶ PFU15 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
Group 4 "OspaVir® + live smallpox vaccine"	Experimental	Biological: Live smallpox vaccine (Smallpox vaccine) + The OspaVir® inactivated smallpox vaccine15 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

Who may qualify

Ages: 18 to 40 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (7 listed)

Consent to participate in the study after written informing.
Healthy volunteers (men and women) aged 18 to 40:

Key exclusion criteria (31 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
VAC∆6 vaccine - оnce at a dose of 10⁶ PFU15 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	Biological	Group 1 "VAC∆6: оnce at a dose of 10⁶ PFU (plaque-forming units)"
VAC∆6 vaccine - once at a dose of 10⁷ PFU15 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	Biological	Group 2 "VAC∆6: once at a dose of 10⁷ PFU"
VAC∆6 vaccine - twice at a dose of 10⁶ PFU15 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	Biological	Group 3 "VAC∆6: twice at a dose of 10⁶ PFU"
Live smallpox vaccine (Smallpox vaccine) + The OspaVir® inactivated smallpox vaccine15 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®.	Biological	Group 4 "OspaVir® + live smallpox vaccine"

Primary outcome

Changes in the percentage of vaccinees with a titer of virus-neutralizing antibodies to vaccinia virus ≥1:40, at specified time intervals.
Time frame: 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.
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.
Recording the number of local reactions.
Time frame: 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.
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.

5 secondary outcomes

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

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2023.
Background: PubMed 26798498Yakubitskiy SN, Kolosova IV, Maksyutov RA, Shchelkunov SN. Attenuation of Vaccinia Virus. Acta Naturae. 2015 Oct-Dec;7(4):113-21.
Background: PubMed 27025484Yakubitskyi 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.
Background: PubMed 28740731Maksyutov 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.
Background: PubMed 32962316Olson 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.
Background: PubMed 29340212Shchelkunova GA, Shchelkunov SN. 40 Years without Smallpox. Acta Naturae. 2017 Oct-Dec;9(4):4-12.
Background: PubMed 32167685Shchelkunov 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.
Background: PubMed 35903306Maksyutov 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.
Background: PubMed 32477596Shchelkunov SN, Shchelkunova GA. Genes that Control Vaccinia Virus Immunogenicity. Acta Naturae. 2020 Jan-Mar;12(1):33-41. doi: 10.32607/actanaturae.10935.
BackgroundMarennikova SS, Shchelkunov SN. Orthopoxviruses pathogenic for humans (monograph). KMK Scientific Press Ltd.1998; 386 p. (in Russian).
BackgroundKolosova 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)
BackgroundYakubitsky 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).
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Vladimir I. Kuzubov, PhD principal investigator

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

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Changes in the percentage of vaccinees with a titer of virus-neutralizing antibodies to vaccinia virus ≥1:40, at specified time intervals. (time frame: 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.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05762523, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2023.