Safety and Efficacy of BARS13 in the Elderly

Sponsor

Advaccine (Suzhou) Biopharmaceuticals Co., Ltd. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04681833

Collaborator

(none)

120

Enrollment

Location

Arms

24.2

Anticipated Duration (Months)

4.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Advaccine Clinical Research are developing a vaccine called BARS13 for the active immunisation of infants (aged 6 months to 5 years old) and the elderly (aged 60-80 years old) for the seasonal prevention of Respiratory Syncytial Virus (RSV) infection. A total of 120 volunteers aged 60 - 80 years (inclusive) will be enrolled in this study, and will be divided into 3 groups (or 'cohorts') of 40 people per cohort. The aim of the study is to evaluate the safety and tolerability of BARS13 in this age group.

Condition or Disease	Intervention/Treatment	Phase
Respiratory Syncytial Virus Infections	Drug: Recombinant Respiratory Syncytial Virus Vaccine (BARS13) /placebo Drug: Recombinant Respiratory Syncytial Virus Vaccine (BARS13) Drug: Placebo	Phase 2

Detailed Description

Advaccine Clinical Research is developing a recombinant Respiratory Syncytial Virus (rRSV) vaccine - BARS13 for the protection of children (6 months to 5 years old) and the elderly from RSV infection.

This is a two centre, randomised, double-blind, placebo-controlled study in healthy adults aged 60-80 years old to evaluate the safety and immunogenicity of the rRSV investigational vaccine, BARS13.

This study will be conducted in two centres in Australia with CMAX as the coordinating site.

Vaccinations for all participants will occur before local Australian RSV peak season (winter/early spring). A total of up to 120 eligible participants will be enrolled administered by IM injection to the deltoid region of the arm. Cohort 1 (low repeat dose) includes one dose of 10micrograms of the vaccine on one arm and one dose of placebo on the other arm given sequentially on Day 1 and 29. Cohort 2 (high repeat dose) includes one dose of 10micrograms of the vaccine on each arm given sequentially on Day 1 and 29. Cohort 3 (high repeat multiple dose) includes one dose of 10microgarms of vaccine to each arm sequentially on Day 1, 29 and 57.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Active: One dose of 10 μg rRSV G protein/10 μg CsA administered by IM injection to the deltoid region of one arm, and one dose of placebo by IM injection to the deltoid region of the other arm, given sequentially (10 μg rRSV G protein/10 μg CsA in total for each vaccination) on Day 1 and 29. Placebo: One dose administered by IM injection to both arms, on Day 1 and 29. Active: One dose of 10 μg rRSV G protein/10 μg CsA administered by IM injection to the deltoid region of each arm, given sequentially (20 μg rRSV G protein/20 μg CsA in total for each vaccination) on Day 1 and 29. Placebo: One dose administered by IM injection to both arms, on Day 1 and 29. Active: One dose of 10 μg rRSV G protein/10 μg CsA administered by IM injection to the deltoid region of each arm, given sequentially (20 μg rRSV G protein/20 μg CsA in total for each vaccination) on Day 1, Day 29 and Day 57. Placebo: One dose administered by IM injection to both arms, on Day 1, Day 29 and Day 57.Active: One dose of 10 μg rRSV G protein/10 μg CsA administered by IM injection to the deltoid region of one arm, and one dose of placebo by IM injection to the deltoid region of the other arm, given sequentially (10 μg rRSV G protein/10 μg CsA in total for each vaccination) on Day 1 and 29. Placebo: One dose administered by IM injection to both arms, on Day 1 and 29. Active: One dose of 10 μg rRSV G protein/10 μg CsA administered by IM injection to the deltoid region of each arm, given sequentially (20 μg rRSV G protein/20 μg CsA in total for each vaccination) on Day 1 and 29. Placebo: One dose administered by IM injection to both arms, on Day 1 and 29. Active: One dose of 10 μg rRSV G protein/10 μg CsA administered by IM injection to the deltoid region of each arm, given sequentially (20 μg rRSV G protein/20 μg CsA in total for each vaccination) on Day 1, Day 29 and Day 57. Placebo: One dose administered by IM injection to both arms, on Day 1, Day 29 and Day 57.

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.

Primary Purpose:

Prevention

Official Title:

A Randomised, Double-blind, Placebo-controlled, Dose-ranging Phase II Study in 60 to 80-Year-Old Adults to Assess the Safety and Immunogenicity of BARS13

Actual Study Start Date :

May 24, 2021

Anticipated Primary Completion Date :

Sep 30, 2022

Anticipated Study Completion Date :

Jun 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1: BARS13 low repeat dose Active: One dose of 10 μg rRSV G protein/10 μg CsA administered by IM injection to the deltoid region of one arm, and one dose of placebo by IM injection to the deltoid region of the other arm, given sequentially (10 μg rRSV G protein/10 μg CsA in total for each vaccination) on Day 1 and 29.	Drug: Recombinant Respiratory Syncytial Virus Vaccine (BARS13) /placebo Low Repeat Dose
Placebo Comparator: Cohort 1: BARS13 placebo low repeat dose Placebo: One dose administered by IM injection to both arms, on Day 1 and 29.	Drug: Placebo Liquid diluent/Lyophilised Powder
Experimental: Cohort 2: BARS13 high repeat dose Active: One dose of 10 μg rRSV G protein/10 μg CsA administered by IM injection to the deltoid region of each arm, given sequentially (20 μg rRSV G protein/20 μg CsA in total for each vaccination) on Day 1 and 29.	Drug: Recombinant Respiratory Syncytial Virus Vaccine (BARS13) High Repeat Dose/High Repeat Multiple Dose
Placebo Comparator: Cohort 2: BARS13 placebo high repeat dose Placebo: One dose administered by IM injection to both arms, on Day 1 and 29.	Drug: Placebo Liquid diluent/Lyophilised Powder
Experimental: Cohort 3: BARS13 high repeat multiple dose Active: One dose of 10 μg rRSV G protein/10 μg CsA administered by IM injection to the deltoid region of each arm, given sequentially (20 μg rRSV G protein/20 μg CsA in total for each vaccination) on Day 1, Day 29 and Day 57.	Drug: Recombinant Respiratory Syncytial Virus Vaccine (BARS13) High Repeat Dose/High Repeat Multiple Dose
Placebo Comparator: Cohort 3: BARS13 placebo high repeat multiple dose Placebo: One dose administered by IM injection to both arms, on Day 1, Day 29 and Day 57.	Drug: Placebo Liquid diluent/Lyophilised Powder

Outcome Measures

Primary Outcome Measures

Incidence and severity of vaccine-related AEs including the following solicited AEs [From baseline (Day 1) to the end of Day 7.]
Incidence and severity of local reactions (pain, tenderness, erythema, swelling, other e.g. ulceration, scabs, bruising,itching and paraesthesia) at the site of vaccination; Incidence and severity of systemic reactions (fatigue, myalgia, malaise, fever, rigors, arthralgia, nausea, diarrhoea, light-headedness, dizziness, hypersensitivity and headache). Any 'solicited' AE with onset outside the specified 7-day period of follow-up will be reported as an unsolicited AE.
Incidence and severity of vaccine-related AEs including the following solicited AEs [From Day 28 to the end of Day 35.]
Incidence and severity of local reactions (pain, tenderness, erythema, swelling, other e.g. ulceration, scabs, bruising,itching and paraesthesia) at the site of vaccination; Incidence and severity of systemic reactions (fatigue, myalgia, malaise, fever, rigors, arthralgia, nausea, diarrhoea, light-headedness, dizziness, hypersensitivity and headache). Any 'solicited' AE with onset outside the specified 7-day period of follow-up will be reported as an unsolicited AE.
Incidence and severity of vaccine-related AEs including the following solicited AEs [From Day 57 to the end of Day 64 (only for multiple high repeat dose group).]
Incidence and severity of local reactions (pain, tenderness, erythema, swelling, other e.g. ulceration, scabs, bruising,itching and paraesthesia) at the site of vaccination; Incidence and severity of systemic reactions (fatigue, myalgia, malaise, fever, rigors, arthralgia, nausea, diarrhoea, light-headedness, dizziness, hypersensitivity and headache). Any 'solicited' AE with onset outside the specified 7-day period of follow-up will be reported as an unsolicited AE.

Secondary Outcome Measures

Occurrence of AEs [From baseline (Day 1) to the end of Day 85.]
An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment.

Other Outcome Measures

Occurrence of any SAE [Through study completion, an average of 1 year.]
A SAE is any untoward medical occurrence that, at any dose: • Results in death; • Is life-threatening, (NOTE: The term 'life-threatening' in the definition of 'serious' refers to an event/reaction in which the participant was at risk of death at the time of the event/reaction; it does not refer to an event/reaction which hypothetically might have caused death, if it were more severe); • Requires inpatient hospitalization or prolongation of an existing hospitalization; • Results in persistent or significant disability/incapacity; • Is a congenital anomaly/birth defect; • Is a medically important event or reaction.
Occurrence of any clinically significant (CS) clinical laboratory abnormalities [From baseline (Day 1) to the end of Day 7.]
Measured as Toxicity Grade ≥1
Occurrence of any clinically significant (CS) clinical laboratory abnormalities [From Day 28 to the end of Day 35.]
Measured as Toxicity Grade ≥1
Occurrence of any clinically significant (CS) clinical laboratory abnormalities [From Day 57 to the end of Day 64 (only for multiple high repeat dose group).]
Measured as Toxicity Grade ≥1

Eligibility Criteria

Criteria

Ages Eligible for Study:

60 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Participants who meet all of the following criteria at screening are eligible to participate in the study:
Healthy male or female adults, or adults with stable chronic disease aged 60 to 80 years old, inclusive.
Body mass index (BMI) ≤ 40 kg/m2.
Screening 12-lead ECG must be within normal range (QT interval corrected using Fridericia's formula [QTcF] males ≤ 450 msec; females ≤ 470 msec) or with abnormalities, which are not hazardous to the patient according to the opinion of the Investigator at the screening visit.
Haematology, serum chemistry, coagulation and urinalysis test results not deviating from the normal reference range by age and gender to a clinically relevant extent at screening.
Systolic blood pressure in the range of 90 to 160 mmHg (inclusive) and diastolic blood pressure in the range of 50 to 95 mmHg (inclusive) after 5 minutes in supine position at the screening visit.
Willing and able (on both a physical and cognitive basis) to give informed consent prior to study enrolment.
Able to comply with study requirements; including access to transportation for study visits.
Access to inbound and outbound telephone communication with caregivers and study staff.
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.

Exclusion Criteria:

Participants who meet any of the following criteria are not eligible to participate in the study:
Participation in research involving investigational product (IP) (drug / biologic / device) within 45 days before the planned date of the Day 1 vaccination.
History of a serious reaction to any prior vaccination.
Received any vaccine other than an inactivated or live attenuated influenza vaccine in the 4 weeks preceding the study vaccination; or any RSV vaccine at any time.
Any known or suspected immunosuppressive condition, acquired or congenital, as determined by history and/or physical examination.
Chronic administration (defined as more than 14 continuous days) of immunosuppressants or other immune-modifying drugs within 6 months prior to the administration of the study vaccine.
Positive testing for active human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies, Quantiferon (Tuberculosis [TB] infection).
Positive urine drug screen at screening, or pre-vaccination for any drug of abuse unless there is an explanation acceptable to the PI.
A positive alcohol breathalyser test at screening or pre-vaccination.
Testing result for RSV IgG(GP) above the cut-off value defined in the RSV IgG(GP) ELISA assay protocol.
Administration of immunoglobulins and/or any blood products within the 3 months preceding the administration of the study vaccine or during the study.
Acute disease at the time of enrollment (defined as the presence of a moderate or severe illness with or without fever, or a tympanic temperature ≥38.0°C on the planned day of vaccine administration).
Suspicion or recent history (within one year of planned vaccination) of alcohol or other substance abuse.
Birthmarks, tattoos, wound or other skin conditions over the deltoid region of both arms .
Subject with a history of autoimmune disease or an active autoimmune disease requiring therapeutic intervention.
History of any chronic respiratory illness, including current diagnosis of asthma within 2 years, COPD ≥ Stage 2 exercise induced wheezing, reactive airway disease, emphysema, chronic bronchitis or cystic fibrosis.
Any respiratory illness within 14 days prior to receiving the first dose of study vaccination.
Any active pulmonary infection or other inflammatory conditions, even in the absence of febrile episodes, within 14 days prior to the first study vaccination.