A Phase 1 Randomized, Observer Blind, Placebo Controlled, Dosage-Escalation Single Center Study to Evaluate the Safety and Immunogenicity of an RSV Fusion Glycoprotein (F) Subunit Vaccine in Healthy Adults
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 288
- 试验地点
- 1
- 主要终点
- Geometric Mean Titers (GMTs) of the Serum Anti-RSV Neutralizing Antibody (NAb) Titers
研究概览
简要总结
The purpose of this study is to evaluate the safety and immunogenicity of two doses of the investigational RSV F subunit vaccine administered intramuscularly (IM). In this current Phase 1, first-in-human study, the three different antigen amounts that have been selected will be evaluated in a stepwise manner in three different cohorts (Cohort 1: low dosage of RSV F subunit vaccine, Cohort 2: middle dosage of RSV F subunit vaccine, and Cohort 3: high dosage of RSV F subunit vaccine). In addition, the effect of an adjuvant, either aluminum hydroxide or MF59, and antibody kinetics post-vaccination at different time points will be evaluated as compared to unadjuvanted RSV F subunit vaccine at the same dosage levels.
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 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy males and non-pregnant females 18 to 45 years of age at time of enrollment.
- •Individuals who have given written consent after the nature of the study has been explained according to local regulatory requirements.
- •Individuals in good health as determined by the outcome of the medical history, physical examination and clinical judgment of the investigator.
- •Individuals who can comply with the study procedures and are available for follow up.
排除标准
- •Individuals with any severe chronic or acute disease.
- •Individuals with a history of illness or with an ongoing illness that may pose additional risk to the subject if he/she participates in the study, including the following:
- •History of any chronic respiratory illness, including current diagnosis of asthma within 2 years, exercise induced wheezing, reactive airway disease, emphysema, chronic bronchitis, cystic fibrosis or chronic obstructive pulmonary disease (COPD).
- •Any respiratory illness within 7 days prior to receiving the first study injection.
- •Any active pulmonary infection or other inflammatory conditions, even in the absence of febrile episodes, within 14 days prior to the first study injection.
- •Hepatitis B or hepatitis C infection.
- •Individuals who have had a malignancy or lymphoproliferative disorder within the past 5 years.
- •Individuals with known or suspected impairment of the immune system including but not limited to HIV, autoimmune disorders, immunosuppressive therapy, and diabetes mellitus.
- •Individuals with any history of progressive or severe neurologic disorder, seizure disorder or Guillian-Barré syndrome.
- •Individuals with a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time.
- •Individuals with a BMI > 35 kg/m
- •BMI is to be calculated by the following formula: subject weight at baseline divided by subject height in meters multiplied by the subject height in meters. The numerical result will be rounded to the nearest 0.
- •Individuals who are allergic to any of the vaccine components, or with a history of anaphylaxis after vaccination.
- •Individuals who during the 90 days prior to enrollment receive any medications or other treatments that may adversely affect the immune system such as allergy injections, immune globulin, interferon, immunomodulators, cytotoxic drugs or other drugs known to be frequently associated with significant major organ toxicity.
- •Individuals who receive systemic immunosuppressive agents including steroids. Prior corticosteroid therapy should be discontinued 28 days prior to enrollment. Individuals using inhaled or topical corticosteroids will be permitted.
- •Receipt or donation of blood or blood products 8 weeks prior to vaccination or planned receipt or donation during the study period.
- •Individuals participating in any clinical trial with another investigational product 28 days prior to receiving the first study vaccination or intent to participate in another clinical study at any time during the conduct of this study.
- •Individuals who have received any vaccine 28 days prior to enrollment in this study, or who plan to receive any non-study vaccines within 28 days of the second dose of study vaccine.
- •Individuals with any clinically significant abnormal safety laboratory result, as judged by the investigator.
- •If female, 'of childbearing potential', sexually active and has not used any of the 'acceptable contraceptive methods' for at least two months prior to study entry.
- •Childbearing potential is defined as status post onset of menarche and not meeting any of the following conditions: menopausal for at least two years; sterile status after bilateral tubal ligation for at least one year, immediately after bilateral oophorectomy or after hysterectomy.
- •Acceptable methods of birth control are defined as one or more of the following:
- •Hormonal contraceptives.
- •Barrier each and every time during intercourse.
- •Intrauterine device (IUD).
- •Monogamous relationship with vasectomized partner. Partner must have been vasectomized for at least six months prior to subject's study entry.
- •If female subject of childbearing potential and have a positive urine pregnancy test prior to study vaccinations, or are currently lactating.
- •If female of childbearing potential and sexually active, refusal to use an 'acceptable contraceptive method' through to three weeks after last study vaccination.
- •Individuals with behavioral or cognitive impairment or psychiatric disease that, in the opinion of the investigator, may interfere with the subject's ability to participate in the study.
- •Individuals with a history of drug or alcohol abuse within the past 2 years.
- •Individuals who are acting as study personnel or immediate family members or the spouse of study personnel.
- •Individuals with a body temperature ≥38 °C (≥100.4◦F) within 3 days of intended study vaccination.
- •Individuals with any condition that, in the opinion of the investigator, would interfere with the primary study objectives.
研究组 & 干预措施
RSV F 45 No Adj Group
Healthy female and male subjects, 18 to 45 years of age, who received two doses of an intramuscular injection of the low dose RSV F subunit vaccine [45 μg], with no adjuvant.
干预措施: RSV F subunit 45 μg No adjuvant (Biological)
RSV F 45 Alum Adj Group
Healthy female and male subjects, 18 to 45 years of age, who received two doses of an intramuscular injection of the low dose RSV F subunit vaccine [45 μg], with aluminum hydroxide adjuvant.
干预措施: RSV F subunit 45 μg Aluminum hydroxide adjuvant (Biological)
RSV F 45 MF59 Adj Group
Healthy female and male subjects, 18 to 45 years of age, who received two doses of an intramuscular injection of the low dose RSV F subunit vaccine [45 μg], with MF59 adjuvant.
干预措施: RSV F subunit 45 μg MF59 adjuvant (Biological)
Placebo 1 Group
Healthy female and male subjects, 18 to 45 years of age, who received two doses of an intramuscular injection of saline solution. Subjects were enrolled in a stepwise dosage escalation manner into one of the three cohorts (Cohort 1: low dosage of RSV F subunit vaccine [45 μg], Cohort 2: middle dosage of RSV F subunit vaccine [90 μg], and Cohort 3: high dosage of RSV F subunit vaccine [135 μg]). This placebo group belongs to Cohort 1.
干预措施: Placebo (Drug)
RSV F 90 No Adj Group
Healthy female and male subjects, 18 to 45 years of age, who received two doses of an intramuscular injection of the medium dose RSV F subunit vaccine [90 μg], with no adjuvant.
干预措施: RSV F subunit 90 μg No adjuvant (Biological)
RSV F 90 Alum Adj Group
Healthy female and male subjects, 18 to 45 years of age, who received two doses of an intramuscular injection of the medium dose RSV F subunit vaccine [90 μg], with aluminum hydroxide adjuvant.
干预措施: RSV F subunit 90 μg Aluminum hydroxide adjuvant (Biological)
RSV F 90 MF59 Adj Group
Healthy female and male subjects, 18 to 45 years of age, who received two doses of an intramuscular injection of the medium dose RSV F subunit vaccine [90 μg], with MF59 adjuvant.
干预措施: RSV F subunit 90 μg MF59 adjuvant (Biological)
Placebo 2 Group
Healthy female and male subjects, 18 to 45 years of age, who received two doses of an intramuscular injection of saline solution. Subjects were enrolled in a stepwise dosage escalation manner into one of the three cohorts (Cohort 1: low dosage of RSV F subunit vaccine [45 μg], Cohort 2: middle dosage of RSV F subunit vaccine [90 μg], and Cohort 3: high dosage of RSV F subunit vaccine [135 μg]). This placebo group belongs to Cohort 2.
干预措施: Placebo (Drug)
RSV F 135 No Adj Group
Healthy female and male subjects, 18 to 45 years of age, who received two doses of an intramuscular injection of the high dose RSV F subunit vaccine [135 μg], with no adjuvant.
干预措施: RSV F subunit 135 μg No adjuvant (Biological)
RSV F 135 Alum Adj Group
Healthy female and male subjects, 18 to 45 years of age, who received two doses of an intramuscular injection of the high dose RSV F subunit vaccine [135 μg], with aluminum hydroxide adjuvant.
干预措施: RSV F subunit 135 μg Aluminum hydroxide adjuvant (Biological)
RSV F 135 MF59 Adj Group
Healthy female and male subjects, 18 to 45 years of age, who received two doses of an intramuscular injection of the high dose RSV F subunit vaccine [135 μg], with MF59 adjuvant.
干预措施: RSV F subunit 135 μg MF59 adjuvant (Biological)
Placebo 3 Group
Healthy female and male subjects, 18 to 45 years of age, who received two doses of an intramuscular injection of saline solution. Subjects were enrolled in a stepwise dosage escalation manner into one of the three cohorts (Cohort 1: low dosage of RSV F subunit vaccine [45 μg], Cohort 2: middle dosage of RSV F subunit vaccine [90 μg], and Cohort 3: high dosage of RSV F subunit vaccine [135 μg]). This placebo group belongs to Cohort 3.
干预措施: Placebo (Drug)
结局指标
主要结局
Geometric Mean Titers (GMTs) of the Serum Anti-RSV Neutralizing Antibody (NAb) Titers
时间窗: At Day 57
Immunogenicity was measured in terms of the Geometric mean titers (GMTs) of the serum anti-RSV neutralizing antibody (NAb) titers at Day 57 (28 days after the second dose).
Number of Subjects With Unsolicited Adverse Events (AEs)
时间窗: From Day 1 to Day 28 after each vaccination
An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.
Percentage of Subjects With a ≥ 4-fold Increase in Serum Anti-RSV NAb Titers
时间窗: At Day 57
Immunogenicity was measured in terms of percentage of subjects with a ≥ 4-fold increase in serum anti-RSV NAb titers, from Day 1 (baseline) to Day 57 (28 days after the second dose).
Number of Subjects With Any Solicited Local Symptoms
时间窗: From Day 1 (6 hours) to Day 7 after each vaccination
Assessed solicited local symptoms were: induration, swelling, erythema and pain. Any induration/swelling/erythema = induration/swelling/erythema spreading beyond 25 millimeters (mm) of injection site. Any pain = occurrence of the symptom regardless of intensity grade.
Number of Subjects With Any Solicited Systemic Symptoms and Other Indicators of Reactogenicity
时间窗: From Day 1 (6 hours) to Day 7 after each vaccination
Assessed solicited systemic symptoms were: nausea, fatigue, myalgia, arthralgia, headache, fever (body temperature ≥ 38.0°C), chills, coughing, diarrhea, rhinorrhea and wheezing. Other solicited data included: prevention of pain and/or fever and treatment of pain and/or fever. Any = occurrence of the symptom regardless of intensity grade.
Number of Subjects With Serious Adverse Events (SAEs) and Other Significant AE(s)
时间窗: From study start (Day 1) until study completion (Day 394)
SAEs assessed include medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity, congenital anomaly or birth defect. Any SAE = occurrence of the SAE regardless of intensity grade. Possibly or probably related SAE = SAE assessed by the investigator as possibly or probably related to the study vaccination. Other significant AE(s) assessed include unsolicited medically attended AEs, unsolicited AEs leading to study withdrawal, new onset of chronic diseases (NOCDs) and adverse events of special interest (AESIs). Medically attended AE = an adverse event that leads to an unscheduled visit to a healthcare practitioner. NOCD = an adverse event that represents a new diagnosis of a chronic medical condition that was not present or suspected in a subject prior to study enrollment.
次要结局
- Geometric Mean Titers (GMTs) of the Serum Total Binding Antibody to Each of the RSV Proteins F, G and N(At Day 1, Day 29, Day 57 and Day 181)
- Geometric Mean Titers (GMTs) of the Serum Anti-RSV Neutralizing Antibody (NAb) Titers(At Day 1, Day 29 and Day 181)
- Percentage of Subjects With Serum Anti-RSV NAb Titers Greater Than the 3rd Quartile of Serum Anti-RSV NAb Titers at Day 1(At Day 29, Day 57 and Day 181)
- Percentage of Subjects With a ≥ 4-fold Increase in Serum Anti-RSV NAb Titer(At Day 29 and at Day 181)
- Percentage of Subjects With Serum Total Binding Antibody Titers to Each of the RSV Proteins F, G, and N Greater Than the 3rd Quartile of Serum Total Binding Antibody Titers to RSV Protein F at Day 1(At Day 29, Day 57 and Day 181)
- Ratio of RSV F Serum Nab Titers to Each of the RSV F Serum Total Binding Antibody Titers to RSV Proteins F, G and N(At Day 1, Day 29, Day 57 and Day 181)
- Percentage of Subjects With a ≥ 4-fold Increase in Serum Total Binding Antibody to Each of the RSV Proteins F, G and N(At Day 29, Day 57 and Day 181)