A Phase I, First in Human (FIH), Randomised, Double-blind, Placebo-controlled, Dose-escalation Study to Evaluate Safety, Reactogenicity and Immunogenicity of the Recombinant Respiratory Syncytial Virus Vaccines (BARS13) When Administered Intramuscularly (IM) to Healthy Adult Volunteers
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Occurrence of any clinical laboratory abnormalities (Toxicity grade > or = 1) form baseline (Day 0) to the last visit
Study Overview
Brief Summary
Advanced Vaccine Laboratories Pty Ltd is developing a recombinant Respiratory Syncytial Virus (rRSV) vaccine for the protection of children (6 months to 5 years old) and the elderly from RSV infection. Human RSV infects nearly all children by the age of two years, and it is a leading cause of severe lower respiratory tract (LRT) disease in both paediatric and elderly populations as well as in individuals was immune system is profoundly compromised.
Detailed Description
Advanced Vaccine Laboratories Pty Ltd is developing a recombinant Respiratory Syncytial Virus (rRSV) vaccine for the protection of children (6 months to 5 years old) and the elderly from RSV infection. Human RSV infects nearly all children by the age of two years, and it is a leading cause of severe lower respiratory tract (LRT) disease in both paediatric and elderly populations as well as in individuals was immune system is profoundly compromised. The investigational product BARS13 has not previously been administered to human subjects. The purpose of this study is to evaluate the safety of, and how the body reacts to, BARS13 investigational vaccine when administered in the arm to healthy adult participants aged 18 to 45 years according to a single (at Day 0) or repeat (at Day 0 and Day 30) vaccination schedule, with follow-up occurring for 60 days after the last vaccination.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Double (Participant, Investigator)
Masking Description
This study is double-blinded. Sealed participant-specific code break envelopes will be produced by the unblinded statistician so that the treatment assigned to each participant can be obtained if required, in an emergency only, where knowledge of the randomisation code is required to provide appropriate treatment. The code break envelopes will be retained at the clinical unit in a secure, accessible location. Those blinded to study drug assignment include the sponsor, the PI, clinical study personnel participating in participants' care or clinical evaluations, and the study participants.
Eligibility Criteria
- Ages
- 18 Years to 45 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •A male or female aged 18-45 years (inclusive) at the time of the first vaccination.
- •Able to communicate effectively with study personnel and is considered reliable, willing, and cooperative in terms of compliance with the protocol requirements.
- •Written informed consent signed prior to undertaking any protocol related procedures.
- •Haematology, clinical chemistry and urinalysis test results not deviating from the normal reference range by age and gender to a clinically relevant extent at screening.
- •Males must be surgically sterile (>30 days since vasectomy with no viable sperm), abstinent or, if engaged in sexual relations with a person of child-bearing potential, the participant and his partner must use an acceptable, highly effective, contraceptive method from screening and for a period of at least 3 months after the last dose of study drug. Acceptable methods of contraception are the use of condoms and an effective contraceptive for the female partner that could include: surgical sterilization (e.g., bilateral tubal ligation), hormonal contraception, or intrauterine contraception/device. The PI is to assess the adequacy of methods of contraception on a case-by-case basis.
- •Women of child-bearing potential (WOCBP) must use highly effective contraceptive measures (failure rate of < 1% per year when used consistently and correctly) throughout the study and intend to continue use of contraception for at least 3 months following the last vaccination. Highly effective contraceptive measures could include: combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device, intrauterine hormone releasing system, bilateral tubal occlusion, vasectomised partner, and sexual abstinence. The PI is to assess the adequacy of methods of contraception on a case-by-case basis.
- •Participant in otherwise general good health based on medical history and physical examination, as determined by the PI.
Exclusion Criteria
- •Presence of clinically significant medical history, unstable chronic or acute disease, or physical, or laboratory findings that, in the opinion of the PI may potentially increase the expected risk of exposure to the investigational vaccine, compromise the safety of the participant, or interfere with any aspect of study conduct or interpretation of results.
- •Body Mass Index (BMI) great than or equal to 40 at screening.
- •Significant infection or other acute illness, including fever over 37.5°C/99.5°F on the day of randomisation.
- •Birthmarks, tattoos, wound or other skin conditions over the deltoid region of both arms that, in the PI's opinion, could reasonably obscure and interfere with evaluation of local injection site reactions.
- •Inadequate venous access to allow collection of blood samples.
- •Breastfeeding or pregnant as confirmed by a positive serum beta human chorionic gonadotropin (.-HCG) pregnancy test at screening or positive urine pregnancy test at subsequent clinic visits at time points as delineated in the study schedule.
- •Received any prophylactic or therapeutic vaccine, or investigational drug, within 3 months of first vaccination, or anticipated in the follow up period defined for this study.
- •History of severe allergy (requiring hospital care), severe reaction to any drug or prior vaccination, or any known or suspected allergies or sensitivities to any component of the investigational vaccine or placebo.
- •Immunosuppression caused by disease (such as human immunodeficiency virus [HIV]) or medications, immunosuppressive therapy (such as long-term systemic corticosteroids therapy).
- •History of hepatitis B or hepatitis C infection.
- •History of autoimmune disorder.
- •History of splenectomy or of condition affecting splenic function.
- •History of malignancy of any organ system (other than localised basal cell carcinoma of the skin), treated or untreated, within the past five years, regardless of whether there is evidence of local recurrence or metastases.
- •History of any neurological disorders or seizures.
- •Thrombocytopenia or bleeding disorder contraindicating intramuscular vaccination.
- •Receipt of immunoglobulins or blood products within 3 months of first vaccination.
- •Requirement for antipyretic or analgesic medication on a daily or every other day basis from randomisation through 72 hours after vaccination.
- •History of alcohol or drug abuse or psychiatric disorder that in the opinion of the PI could affect the participants' safety or compliance with study.
- •Positive urine drug screen at screening, or pre-vaccination for any drug of abuse unless there is an explanation acceptable to the PI (e.g. the participant stated in advance that they consumed a prescription or over the counter product which contained the detected drug) and/or the participant had a negative urine drug screen on retest by the pathology laboratory.
- •A positive alcohol breathalyser test at screening or pre-vaccination.
- •Participant unwilling to abstain from blood donation during the course of the study, and/or participation in any research study involving blood sampling (more than 450 mL /unit of blood), or blood donation to the Australian Red Cross Blood Service (ARCBS) or other blood bank during the 2 months prior to the screening visit.
Arms & Interventions
Cohort 1: low dose
IM injection on Day 0 (12 active, 3 placebo); with follow up at 7 days ± 1 day post vaccination and at Day 30 ± 5 days and a final follow up/end of study (EOS) teleconference assessment at Day 60 ± 5 days.
Intervention: Respiratory Syncytial Vaccine (Biological)
Cohort 2: low dose
IM injection on Day 0 and at Day 30 (12 active, 3 placebo) with follow up at 7 days post vaccination (Day 7 ± 1 day and Day 37 ± 1 day) and Day 60 ± 5 days and a final follow up/ EOS teleconference assessment at Day 90 ± 5 days.
Intervention: Placebo (Biological)
Cohort 3: high dose
IM injection on Day 0 (12 active, 3 placebo); with follow up at 7 days ± 1 day post vaccination and at Day 30 ± 5 days and a final follow up/end of study (EOS) teleconference assessment at Day 60 ± 5 days.
Intervention: Respiratory Syncytial Vaccine (Biological)
Cohort 4: high dose
IM injection on Day 0 (12 active, 3 placebo); with follow up at 7 days ± 1 day post vaccination and at Day 30 ± 5 days and a final follow up/end of study (EOS) teleconference assessment at Day 60 ± 5 days.
Intervention: Placebo (Biological)
Outcomes
Primary Outcomes
Occurrence of any clinical laboratory abnormalities (Toxicity grade > or = 1) form baseline (Day 0) to the last visit
Time Frame: 60 days post vaccination
Occurrence of any clinical laboratory abnormalities (Toxicity grade \> or = 1) form baseline (Day 0) to the last visit
Occurrence of any AE during a 30-minute post-vaccination safety observation period
Time Frame: 30 minutes post vaccination on Day 0 and 30
Occurrence of any AE during a 30-day follow-up period after each vaccination.
Incidence of local reactions
Time Frame: 7 days post vaccination
Incidence of the local reactions (pain, tenderness, erythema, swelling, other e.g. ulceration, scabs, redness, induration, ecchymosis, oedema, itching and paraesthesia) at the site of vaccination assessed by patient reported AEs and diary card
Incidence of systemic reactions
Time Frame: 7 days post vaccination
Incidence of the systemic reactions (fatigue, myalgia, malaise, fever, rigors, arthralgia, nausea, diarrhoea, light-headedness, dizziness, hypersensitivity and headache) assessed by patient reported AEs and diary card
Occurrence of any AE during a 30-day follow-up period after each vaccination
Time Frame: 30 days post vaccination
Occurrence of any AE during a 30-day follow-up period after each vaccination.
Occurrence of any Serious Adverse Event (SAE) form baseline (Day 0) to the last visit
Time Frame: 60 days post last vaccination
Occurrence of any Serious Adverse Event (SAE) form baseline (Day 0) to the last visit
Secondary Outcomes
- Humoral response to BARS13: IgG antibody titers (GMFRs) measured by ELISA prior to vaccination (Day 0) and post vaccination at Day 30 (all cohorts) and at Day 60 (cohorts 2 and 4 only)(30 day post each vaccination)
- Humoral response to BARS13: IgG antibody titers (GMTs) measured by ELISA prior to vaccination (Day 0) and post vaccination at Day 30 (all cohorts) and at Day 60 (cohorts 2 and 4 only)(30 day post each vaccination)
- Humoral response to BARS13: IgG antibody titers (GMTs) measured by ELISA prior to vaccination (Day 0) and post vaccination at Day 30 (all cohorts) and at Day 60 (cohorts 2 and 4 only)(Pre-vaccination)
- Humoral response to BARS13: IgG antibody titers (GMFRs) measured by ELISA prior to vaccination (Day 0) and post vaccination at Day 30 (all cohorts) and at Day 60 (cohorts 2 and 4 only)(Pre-vaccination)