Clinical trial NCT02935192: Phase 3 Trial of Serbian Seasonal Influenza Vaccine
Official title: A Phase 3 Double Blinded, Randomized, Placebo- Controlled Study to Examine the Safety and Immunogenicity of a Seasonal Trivalent Split Inactivated Influenza Vaccine Produced by Institute Torlak in 18-65 Year Old Volunteers in Serbia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Influenza
Keywords: seasonal influenza
vaccine
Lead sponsor: Institute of Virology, Vaccines and Sera, Torlak
Sponsor class: OTHER
Collaborators: name: PATH
name: Comac Medical
name: World Health Organization
First posted: 2016-10-17
Enrollment: 480
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: A Phase 3, double-blind, randomized, placebo-controlled trial of a seasonal, trivalent, split, inactivated influenza vaccine produced by InstituteTorlak.

Detailed description: This is a phase 3, double-blind, randomized, placebo- controlled trial with two groups of participants to receive seasonal trivalent split, inactivated influenza vaccine (A/H1N1; A/H3N2 and B) or placebo (phosphate buffered saline). A total of about 480 healthy male and female adults 18 through 65 years of age; 320 participants will be randomized to receive vaccine and160 will receive placebo (a 2:1 ratio). At least 25% of the participants (N=120) will be \>/= 45 years of age (80 vaccine and 40 placebo recipients).

Safety will be assessed in all participants through Day 91. Immunogenicity will be assessed in serum samples obtained at baseline and 21 days after vaccination in a subset of at least 100 individuals randomized to study vaccine and 50 placebo recipients.

Eligibility criteria: Inclusion Criteria:

* Aged 18 to 65 years on the day of screening/enrollment.
* Literate (by self-report) and willing to provide written informed consent.
* Able to attend all scheduled visits and to comply with all trial procedures.
* Healthy or medically stable, as established by medical history and physical examination. For individuals with medical conditions, symptoms/signs, if present must be stable under control or unchanged for the past three months. If medication is used to treat the condition, the medication dose must have been stable for at least one month preceding vaccination.

For female participants:

* Not breast feeding, non-pregnant (based on negative urine pregnancy test) and no plan to become pregnant up to Day 22.
* Women who are not surgically sterile (hysterectomy or tubal ligation) or post-menopausal for more than one year must be willing to use effective contraceptive method to prevent pregnancy until three weeks (Day 22) after vaccination. Effective methods include intrauterine device, hormonal contraceptives (oral, injectable, patch, implant, ring) or double barrier contraceptives (condom or diaphragm with spermicide). Women with credible history of abstinence may be enrolled at the discretion of the investigator.

Exclusion Criteria:

* Participation in another clinical trial involving any therapy within the previous three months or planned enrollment in such a trial during the period of this study.
* Receipt of influenza vaccine in the last 10 months.
* Receipt of any non-study vaccine within four weeks prior to enrollment or refusal to postpone receipt of such vaccines until after the Day 22 visit.
* Receipt of immune globulin or other blood products within three months prior to study enrollment or planned receipt of such products prior to the Day 22 visit.
* Known or suspected congenital or acquired immunodeficiency.
* Chronic administration (defined as more than 14 consecutively-prescribed days) of immunosuppressants or other immune-modulating therapy within six months prior to study enrollment. (For corticosteroids, this means prednisone or equivalent, ≥ 0.5 mg per kg per day; topical steroids are allowed.)
* Unstable illness by history or physical examination that in the opinion of the investigator, might interfere with the conduct or results of the study or pose additional risk to the participant.
* Hypersensitivity after previous administration of any vaccine.
* Suspected or known hypersensitivity to any of the study vaccine components, including chicken or egg protein or antibiotics.
* Bleeding disorder or receipt of anticoagulants in the three weeks preceding enrollment.
* Known active tuberculosis or symptoms of active tuberculosis, regardless of cause (self-report).
* Current alcohol or drug addiction that in the opinion of the Investigator, might interfere with the ability to comply with trial procedures.
* History of Guillain-Barré Syndrome.
* Neoplastic disease or any hematologic malignancy. Allowed: localized skin or prostate cancer that is no longer being treated and is stable at the time of vaccination and participants who have a history of neoplastic disease and who have been disease free for ≥ 5 years.
* Any condition that, in the opinion of the investigator, would increase the health risk to the participant if he/she participates in the study, or would interfere with the evaluation of the study objectives.

Primary outcomes:
measure: Number of Participants With Solicited Adverse Events (Local & Systemic Reactogenicity)
timeFrame: 30-minute post-vaccination period
measure: Number of Participants With Solicited Local Adverse Events (Local Reactogenicity)
timeFrame: 5-day period (Days 1-5) post-vaccination
measure: Number of Participants With Solicited Systemic Adverse Events (Systemic Reactogenicity)
timeFrame: 5-day period (Days 1-5) post-vaccination
measure: Number of Participants With Unsolicited Adverse Events
timeFrame: Within 21 days post vaccination
measure: Number of Participants With Serious Adverse Events (SAE)
timeFrame: Over the entire study period (Day 91)
measure: Number and Percentage of Seroconverted Subjects
timeFrame: Day 22
measure: Number and Percentage of Participants With a HAI Antibody Titer ≥1:40 (Seroprotection)
timeFrame: Day 1 and Day 22
measure: Geometric Mean Titers (GMTs) of Serum HAI Antibodies
timeFrame: Day 1 and Day 22
measure: Geometric Mean Fold Rises (GMFRs) of Serum HAI Antibodies
timeFrame: Day 1 and Day 22
Secondary outcomes:
Other outcomes:
Locations:
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia: Clinic for Infectious and Tropical Diseases
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia: Clinic for Pulmonology
city: Belgrade
country: Serbia
facility: Institute for Students' Healthcare
city: Belgrade
country: Serbia
facility: Institute of Health Care of Workers of the Ministry of Internal Affairs
city: Belgrade
country: Serbia
facility: Jevremova Special gynecology hospital with maternity
city: Vršac
country: Serbia
facility: General Hospital Vrsac
Study officials:
affiliation: Clinical Center of Serbia, Clinic for Infectious and Tropical Diseases
name: Goran Stevanovic, MD
role: STUDY_CHAIR
References:
citation: Stevanovic G, Obradovic A, Ristic S, Petrovic D, Milenkovic B, Mitrovic D, Vignjevic SF, Ilic K, Stoiljkovic V, Lavadinovic L, Pelemis M, Petrovic S, Vidmanic A, Popovic O, Eremic N, Sparrow E, Torelli G, Socquet M, Holt R, Ilieva-Borisova Y, Tang Y, Scorza FB, Flores J, Rathi N. Safety and immunogenicity of a seasonal trivalent inactivated split influenza vaccine: a double blind, phase III randomized clinical trial in healthy Serbian adults. Ther Adv Vaccines Immunother. 2020 May 25;8:2515135520925336. doi: 10.1177/2515135520925336. eCollection 2020.