Assessing the Effectiveness of Vaccines in Preventing Adult RSV-caused Lower Respiratory Tract Disease (LRTD)
Conditions
Brief summary
This is a phase III clinical trial with a multicenter, randomized, blinded, placebo-controlled design to evaluate the protective efficacy, safety, and immunogenicity of the recombinant respiratory syncytial virus (RSV) vaccine (CHO cell) in individuals aged 60 and above. Sample Size and Trial Grouping: This trial plans to enroll 25,000 trial participants aged ≥60 years (with approximately 30% aged 70 and above), with a relatively balanced gender distribution. Participants of each age group (60-69 years old, ≥70 years old) will be randomly assigned to the trial group and the placebo group in a 1:1 ratio. The sample size for the immunogenicity subgroup is not calculated based on statistical power. Referring to similar clinical trials of RSV vaccines and in conjunction with the immunogenicity observation objectives of this trial, the first 300 trial participants (including those from both age groups) from each site under the leading institution will be included in the immunogenicity subgroup, for a total of 1,200 participants.
Detailed description
A total of 25000 adults aged 60 years and above will be enrolled, stratified into 60-69 and ≥70 years of age. All Participants will randomly receive investigational vaccine or placebo at a ratio of 1:1. Efficacy and safety will be assessed in all Participants, while immunogenicity will be assessed in a subset of 1200 Participants in a selected trial site.
Interventions
BIOLOGICALSodium Chloride Injection 0.9%
The placebo is a 0.9% sodium chloride solution. Each person is to receive 0.5mL for intramuscular injection, with the injection site being the deltoid muscle on the lateral side of the upper arm. Intravenous injection is strictly prohibited. The remaining 0.9% sodium chloride solution (approximately 9.5mL) should be disposed of as waste.
Test vaccine BW-201 (Adj 1): After mixing the "recombinant respiratory syncytial virus vaccine adjuvant injection" upside down, fully aspirate and inject it into the "RSV vaccine" lyophilized powder for re-dissolution. Slowly rotate the vial to mix, and use it after complete dissolution. After mixing the antigen and adjuvant, store them in a refrigerator at 2°C-8°C in the dark and use them within 4 hours. Before use, they need to be mixed again. If the mixture of antigen and adjuvant is left at room temperature (not exceeding 25°C), it needs to be used within 30 minutes. After mixing 1 bottle of adjuvant solution according to the above steps, aspirate the entire content and add it to the antigen, followed by mixing. Each person should receive 0.5mL per injection, administered intramuscularly into the deltoid muscle on the lateral side of the upper arm. Intravenous injection is strictly prohibited.
Sponsors
Beijing BeneWill Technology Development Co., Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Sample size considerations: Given that a comprehensive and functional infection surveillance network for RSV has not yet been established domestically, the incidence rate of LRTD caused by RSV infection in this trial is unpredictable. This trial reviewed randomized controlled trials of commercially available RSV vaccines abroad, where the incidence rate in the placebo group ranged from 0.35% to 0.8%. Based on the estimated incidence rate of RSV-LRTD in similar clinical trials, this trial assumes an incidence rate of approximately 0.35% during the first epidemic season. It is expected that the vaccine will achieve a protective efficacy of 70% 14 days after one dose of the trial vaccine in individuals aged 60 and above. The ratio of the test group to the control group is 1:1, and the total type I error rate is set at one-sided α=0.025. An interim analysis will be considered when at least two-thirds of the primary efficacy endpoint cases of RSV-LRTD are observed during the first epidemic
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
(In cases where the required number of participants has not been met, if the criteria described in the "\*" option are not met during screening, the visit can be rescheduled) 1. \*At the time of enrollment, participants must be aged 60 or above, of either gender, and able to provide legal identification; 2. Have the ability to understand the clinical trial procedures, voluntarily agree to participate, and sign the informed consent form; 3. Be able to cooperate and participate in all scheduled follow-ups as required by the protocol; 4. Female trial participants should have undergone menopause or sterilization surgery; \[Menopause is defined as continuous cessation of menstruation for ≥12 months without alternative medical measures; sterilization surgery includes bilateral tubal ligation, bilateral oophorectomy, or hysterectomy\]. 5. Trial participants who are judged by the researchers to have stable health conditions. \[Stable health conditions refer to those with chronic diseases that have been stable for the past 3 months prior to enrollment, such as diabetes, hypertension, chronic obstructive pulmonary disease, and asthma. If the researchers judge the condition to be stable, the participant is allowed to participate in this trial\].
Exclusion criteria
(If the enrollment requirement is not met, and the criteria described in the "\*" option are met during screening, the visit can be rescheduled) 1. \*On the day before vaccination, the on-site measured temperature is \>37.0℃ (axillary temperature); 2. \*Upon research, the on-site measured blood oxygen saturation (SpO2) is ≤90%; 3. Have previously received or plan to receive any marketed or experimental RSV vaccine/RSV monoclonal antibody; 4. A history of RSV infection confirmed within 6 months prior to enrollment; 5. \*Having used or planning to use any non-specific immunoglobulin and/or blood products containing non-specific immunoglobulin (such as whole blood, plasma) within 3 months before enrollment or during the trial period; 6. \*Have used other investigational or unregistered products (drugs or vaccines) within one month before enrollment, or are currently participating in other clinical trials or plan to participate in other clinical trials during the trial period; 7. \*Having used immunosuppressants or other immunomodulatory drugs for a prolonged period (continuous use ≥14 days) within 3 months before enrollment or during the planned trial period \[such as systemic glucocorticoids for ≥14 days, with a dose ≥2mg/kg/day or ≥20mg/day of prednisone or equivalent to prednisone; however, topical medications (such as ointments, eye drops, inhalers, or nasal sprays) are allowed, and the dose of topical medications must not exceed the recommended dose as stated in the instructions\]; 8. \*Having received a live attenuated vaccine within 30 days before enrollment or planning to receive one within 30 days after enrollment, or having received any non-live vaccine other than the trial vaccine within 14 days before enrollment or planning to receive one within 14 days after enrollment; 9. \*Having an acute disease or being in an acute exacerbation phase of a chronic disease within 3 days before enrollment, or using antipyretic analgesics (excluding medications used to control current diseases and which, in the investigator's judgment, are not expected to affect the interpretation of trial results, such as aspirin used for the treatment of coronary heart disease) or antiallergic medications (e.g., acetaminophen, ibuprofen, aspirin, loratadine, cetirizine, etc.); 10. Individuals with a history of severe allergic reactions requiring medical intervention to any vaccine or medication \[such as anaphylactic shock, allergic laryngeal edema, allergic purpura, thrombocytopenic purpura, local allergic necrotic reaction (Arthus reaction), etc.\] or known allergies to any component of the trial vaccine \[citric acid, sodium citrate, sodium chloride, sucrose, polysorbate 80 (II), mannitol, squalene, sorbitan trioleate (Span 85), water for injection\]; 11. Previous or current congenital or acquired immune deficiency diseases (such as AIDS), human immunodeficiency virus (HIV) infection, systemic lupus erythematosus, or other autoimmune diseases that may affect the trial evaluation as assessed by the investigator (such as a history of inflammatory demyelinating neuropathy like Guillain-Barré syndrome); other diseases affecting immune function (such as asplenia or functional asplenia); 12. Previous or current severe or uncontrollable cardiovascular and cerebrovascular diseases, liver and kidney diseases, respiratory system diseases, diabetes with complications, malignant tumors \[for patients with lacunar cerebral infarction or cerebral infarction without sequelae, or certain malignant tumors (such as papillary thyroid carcinoma, early-stage cervical cancer, basal cell carcinoma, and squamous cell carcinoma of the skin), those who have been stable and relapse-free for 5 years prior to enrollment after careful assessment by the researchers are allowed to be enrolled\]; 13. Currently suffering from or having previously suffered from convulsions, epilepsy (specifically other convulsions and epilepsy other than febrile seizures in children), acute disseminated encephalomyelitis, or other neurological diseases; or having a history of mental illness affecting normal behavior, or a family history of the aforementioned diseases with a genetic predisposition; 14. Suffering from thrombocytopenia, coagulation dysfunction, or any condition that may constitute a contraindication to intramuscular injection; 15. \*Elevated blood pressure (systolic blood pressure ≥160mmHg and/or diastolic blood pressure ≥100mmHg, regardless of medication use) measured through on-site physical examination; 16. Individuals with alcoholism or alcohol dependence (such as an inability to control drinking behavior, and a dependency on alcohol) or drug abuse; 17. Other conditions that researchers consider unsuitable for participation in clinical trials.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The first-time incidence rate per person-year of Lower Respiratory Tract Disease (LRTD). | From 14 days after vaccination until the end of S1, the evaluation period can last up to 12 months. | The yearly rate of first-time RSV-LRTD confirmed by RT-PCR from 14 days after vaccination until the end of S1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The first time someone gets severe lower respiratory tract disease (sLRTD) each year per person. | From 14 days after vaccination until the end of S1, the evaluation period can last up to 12 months. | The annual incidence rate per person for the first occurrence of RSV-sLRTD confirmed by RT-PCR from 14 days after vaccination until the end of S1. |
| The first occurrence rate of acute respiratory infections (ARI) per person per year. | From 14 days after vaccination until the end of S1, the evaluation period can last up to 12 months. | The annual incidence rate of first-time RSV-ARI confirmed by RT-PCR occurring from 14 days after vaccination until the end of S1. |
| The incidence of the first occurrence of LRTD per person per year. | From 14 days after vaccination to the end of S1, the assessment period can last up to 12 months. | The annual incidence per person of first-time, RT-PCR-confirmed RSV A or RSV B subtype-related LRTD from 14 days after vaccination until the end of S1; |
| The incidence of the first occurrence of sLRTD per person per year. | From 14 days after vaccination to the end of S1, the assessment period can last up to 12 months. | The incidence rate per person-year of first-time RSV A and RSV B related sLRTD confirmed by RT-PCR from 14 days after vaccination until the end of S1; |
| The incidence rate of the first ARI each year per person. | From 14 days after vaccination to the end of S1, the assessment period can last up to 12 months. | The incidence rate per person-year of RSV A and RSV B related ARI confirmed by RT-PCR, occurring for the first time from 14 days after vaccination until the end of S1. |
| Occurrence of adverse events (AEs) | Within 30 days after vaccination | The occurrence of adverse events (AE) within 30 days after vaccination |
| Occurrence of solicited adverse events | Within 7 days after vaccination | Occurrence of solicited AEs within 7 days after vaccination |
| Occurrence of unsolicited AEs | Within 30 days after vaccination | Occurrence of unsolicited AEs within 30 days after vaccination |
| How often serious adverse events (SAEs) and adverse events of special interest (AESIs) happen | Within 12 months after vaccination | The occurrence of serious adverse events (SAE) and adverse events of special interest (AESI) within 12 months after vaccination. |
| Immunogenicity (Immunogenicity Subgroup) | 30 days and 12 months after vaccination. | Geometric mean titers (GMT) of neutralizing antibodies against RSV A and RSV B subtypes |
Countries
China
Contacts
CONTACTZhao Gao, Master of Medicine
STUDY_DIRECTORZhao Gao, Master of Medicine
Hebei Provincial Center for Disease Control and Prevention
Outcome results
None listed