A Randomized, Blinded, Placebo-Controlled Phase I Clinical Trial to Evaluate the Safety and Preliminary Immunogenicity of Recombinant Respiratory Syncytial Virus Vaccine (CHO Cell) in Adults Aged 18 Years and Older
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 128
- 试验地点
- 1
- 主要终点
- Incidence of immediate adverse events
研究概览
简要总结
This phase 1 study in China will evaluate the Safety and Preliminary Immunogenicity of Recombinant RSV Vaccine (CHO Cell) in Adults Aged 18 Years and Older
详细描述
This is a single-center, randomized, blinded, placebo-controlled trial. A total of 128 trial participants aged 18 years and older will be enrolled: 64 trial participants aged 18-59 years and 64 trial participants aged 60 years and older. Each age stratum will be divided into four cohorts, for a total of eight cohorts: low-dose antigen cohorts, high-dose antigen cohorts , adjuvant-only cohorts, and low-dose antigen + adjuvant cohorts in the 18-59-year and 60-years-and-older strata.
Eligible trial participants in each cohort will be randomized 3:1 on Day 0 to receive one dose of investigational vaccine (low-dose antigen, high-dose antigen, adjuvant, or low-dose antigen + adjuvant) or placebo. Enrollment will proceed in the order of adults (18-59 years) to older adults (60 years and older), low dose to high dose, and antigen to adjuvant to antigen + adjuvant.
To ensure the safety of the study population, the first four trial participants enrolled in each cohort will be designated as sentinel trial participants and randomized 3:1 to investigational vaccine or placebo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Adults aged 18 years and older who reside in the local area and can provide legal proof of identity; sex is not restricted;
- •Trial participants understand the informed consent form and the vaccine to be administered, voluntarily agree to participate and sign the informed consent form, and are able to use a thermometer and ruler and complete the diary card and contact card as required. If a participant is unable to sign the informed consent form independently because of limited literacy, the informed consent process and signature may be completed with the assistance of an impartial witness;
- •Able to communicate effectively with the investigator and understand and comply with all trial requirements;
- •Women of childbearing potential (see Appendix 2 for the definition) must have used effective contraception for 2 weeks before enrollment, have a negative urine pregnancy test before investigational vaccine administration (women not of childbearing potential are exempt), and voluntarily agree to continue using at least one effective contraceptive method for 6 months after vaccination. Effective contraception includes oral contraceptives, injectable or implantable contraception, long-acting local contraceptives, hormone patches, intrauterine devices (IUDs), sterilization, abstinence, male condoms, diaphragms, cervical caps, etc. Male trial participants must agree to use effective contraception with female partners of reproductive potential from the screening visit until 6 months after immunization.
排除标准
- •Trial participants meeting any of the following exclusion criteria may not be enrolled:
- •Abnormal pre-vaccination laboratory tests (complete blood count, blood biochemistry, coagulation function, C-reactive protein, or urinalysis) or 12-lead electrocardiogram findings that, based on medical history and clinical presentation, render the person unsuitable for vaccination in the investigator's judgment;
- •Abnormal skin at the vaccination sites on both arms at the vaccination visit (e.g., inflammation, induration, erythema/swelling, or extensive scars);
- •Hypertension not controlled by medication, or pre-enrollment systolic blood pressure of at least 160 mmHg and/or diastolic blood pressure of at least 100 mmHg;
- •Axillary temperature of at least 37.1 degrees C on the day of vaccination; fever, acute illness, or an acute exacerbation of chronic disease within the preceding 3 days; or use of antipyretic/analgesic or anti-allergy medications within the preceding 3 days;
- •Communicable period of any infectious disease, acute infection, or acute phase of chronic infection (e.g., active untreated tuberculosis) (by interview);
- •Laboratory-confirmed RSV infection within the previous 12 months, or previous receipt of, or planned receipt of, any marketed or investigational RSV vaccine or RSV monoclonal antibody;
- •Documented history of atrial fibrillation;
- •History of severe allergic reactions requiring medical intervention [e.g., anaphylactic shock, allergic laryngeal edema, allergic purpura, thrombocytopenic purpura, or local allergic necrotic reaction (Arthus reaction)]; history of allergy to any component of the investigational vaccine; or history of other severe adverse reactions to vaccination;
- •Physician-diagnosed abnormal coagulation function (e.g., coagulation factor deficiency, coagulation disease, or platelet abnormalities) or coagulation disorder that may contraindicate intramuscular injection;
- •Anatomic or functional asplenia, or asplenia/splenectomy resulting from any condition;
- •Current diagnosed neurologic or psychiatric disorder (including dementia, schizophrenia, or bipolar disorder), previous diagnosis of epilepsy or seizures (excluding febrile seizures in childhood), or other neurologic disease considered unsuitable for trial participation by the investigator;
- •Diagnosed congenital or acquired immunodeficiency disease, such as human immunodeficiency virus infection, lymphoma, leukemia, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, or another immune disease that may affect the trial assessment in the investigator's judgment;
- •Long-term use (continuous use for 2 weeks or more) of immunosuppressants or other immunomodulatory medication within 6 months before enrollment or planned within 30 days after vaccination, such as long-term systemic corticosteroid therapy (continuous use for 2 weeks or more at a dose of at least 2 mg/kg/day or at least 20 mg/day of prednisone or equivalent). Topical medication (e.g., ointments, eye drops, inhalants, or nasal sprays) is permitted provided the labeled recommended dose is not exceeded;
- •Known serious congenital malformation; developmental disorder or clinically diagnosed serious chronic disease (e.g., Down syndrome, diabetes with complications, sickle cell anemia, or neurologic disease);
- •History of immune-mediated demyelinating disease, including but not limited to multiple sclerosis, neuromyelitis optica, acute disseminated encephalomyelitis, transverse myelitis, or Guillain-Barre syndrome;
- •Known or suspected serious disease considered by the investigator to affect vaccination, including serious respiratory, digestive, endocrine, immune, cardiovascular, hepatic or renal disease, malignancy, or serious skin disease;
- •Pregnant or breastfeeding women, or women planning to conceive within 6 months after vaccination;
- •Receipt of blood products, including whole blood, plasma, gamma globulin, or immunoglobulin, within 3 months before vaccination, or plans to receive such treatment during the trial;
- •Receipt of a live attenuated vaccine within 28 days before or planned within 28 days after investigational vaccine administration, or receipt of any non-live vaccine within 14 days before or planned within 14 days after investigational vaccine administration;
- •Participation in another clinical trial within 6 months before the screening visit, or plans to participate in another clinical trial during this trial;
- •Plans to move before the end of the trial or to be away from the local area for an extended period during scheduled trial visits;
- •Any condition that, in the investigator's judgment, may affect the trial assessment.
研究组 & 干预措施
Low-Dose Antigen Cohort in subjects aged 18-59 years
Subjects aged 18-59 years will receive single dose of Recombinant RSV Vaccine (CHO Cell), by IM injection into the deltoid muscle of the upper arm.
干预措施: Recombinant RSV Vaccine (CHO Cell) (Biological)
High-Dose Antigen Cohort in subjects aged 18-59 years
Subjects aged 18-59 years will receive double dose of Recombinant RSV Vaccine (CHO Cell), by IM injection into the deltoid muscle of the upper arm.
干预措施: Recombinant RSV Vaccine (CHO Cell) (Biological)
Adjuvant Cohort in subjects aged 18-59 years
Subjects aged 18-59 years will receive single dose of Adjuvant Suspension, by IM injection into the deltoid muscle of the upper arm.
干预措施: Adjuvant Suspension (Biological)
Low-Dose Antigen + Adjuvant Cohort in subjects aged 18-59 years
Subjects aged 18-59 years will receive single dose of Recombinant RSV Vaccine (CHO Cell) with Adjuvant Suspension, by IM injection into the deltoid muscle of the upper arm.
干预措施: Recombinant RSV Vaccine (CHO Cell) with Adjuvant Suspension (Biological)
Placebo group in subjects aged 18-59 years
Subjects aged 18-59 years will receive single dose of placebo, by IM injection into the deltoid muscle of the upper arm.
干预措施: Saline solution (Biological)
Low-Dose Antigen Cohort in subjects aged ≥60 years
Subjects aged ≥60 years will receive single dose of Recombinant RSV Vaccine(CHO Cell), by IM injection into the deltoid muscle of the upper arm.
干预措施: Recombinant RSV Vaccine (CHO Cell) (Biological)
High-Dose Antigen Cohort in subjects aged ≥60 years
Subjects aged ≥60 years will receive single dose of Recombinant RSV Vaccine(CHO Cell), by IM injection into the deltoid muscle of the upper arm.
干预措施: Recombinant RSV Vaccine (CHO Cell) (Biological)
Adjuvant Cohort in subjects aged ≥60 years
Subjects aged ≥60 years will receive single dose of Adjuvant Suspension, by IM injection into the deltoid muscle of the upper arm.
干预措施: Adjuvant Suspension (Biological)
Low-Dose Antigen + Adjuvant Cohort in subjects aged ≥60 years
Subjects aged ≥60 years will receive single dose of Recombinant RSV Vaccine (CHO Cell) with Adjuvant Suspension, by IM injection into the deltoid muscle of the upper arm.
干预措施: Recombinant RSV Vaccine (CHO Cell) with Adjuvant Suspension (Biological)
Placebo group in subjects aged ≥60 years
Subjects aged ≥60 years will receive single dose of placebo, by IM injection into the deltoid muscle of the upper arm.
干预措施: Saline solution (Biological)
结局指标
主要结局
Incidence of immediate adverse events
时间窗: Within 30 minutes after vaccination
Incidence of all adverse events within 30 minutes after vaccination
Incidence of solicited AEs
时间窗: Within 0-14 days after vaccination
Incidence of solicited (local and systemic) adverse events within 14 days after vaccination
Incidence of unsolicited AEs
时间窗: Within 30 days after vaccination
Incidence of unsolicited adverse events within 30 days after vaccination
次要结局
- Incidence of clinically significant abnormalities in clinical laboratory tests(4 days after vaccination)
- Incidence of clinically significant abnormal findings on 12-lead electrocardiograms(4 days, 14 days, 30 days after vaccination)
- Occurrence of serious adverse events (SAEs)(Within 24 months after vaccination)
- Occurrence of adverse events of special interest (AESIs)(Within 12 months after vaccination)
- GMT of Neutralizing Antibody against RSV serotype A and B(30 days after vaccination)
- GMFR of Neutralizing Antibody against RSV serotype A and B(30 days after vaccination)
- SCR of Neutralizing Antibody against RSV serotype A and B(30 days after vaccination)
- GMC of pre-F protein-binding antibodies(30 days after vaccination)
- GMFR of pre-F protein-binding antibodies(30 days after vaccination)
- SCR of pre-F protein-binding antibodies(30 days after vaccination)
- GMT of Neutralizing Antibody against RSV serotype A and B(14 days, 3 months, 6 months,12 months, 18 months and 24 months after vaccination)
- GMFR of Neutralizing Antibody against RSV serotype A and B(14 days, 3 months, 6 months,12 months, 18 months and 24 months after vaccination)
- SCR of Neutralizing Antibody against RSV serotype A and B(14 days, 3 months, 6 months,12 months, 18 months and 24 months after vaccination)
- GMC of pre-F protein-binding antibodies(14 days, 3 months, 6 months,12 months, 18 months and 24 months after vaccination)
- GMFR of pre-F protein-binding antibodies(14 days, 3 months, 6 months,12 months, 18 months and 24 months after vaccination)
- SCR of pre-F protein-binding antibodies(14 days, 3 months, 6 months,12 months, 18 months and 24 months after vaccination)
- The frequencies of antigen-specific T cells secreting IL-2 and IFN-γ(14 days, 30 days after vaccination)
- The frequencies of antigen-specific CD4+ and CD8+ T cells expressing IL-2 and IFN-γ(14 days, 30 days after vaccination.)