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
Overview
- Phase
- Phase 1
- Intervention
- RSV F subunit 45 μg No adjuvant
- Conditions
- Respiratory Syncytial Virus (RSV)
- Sponsor
- GlaxoSmithKline
- Enrollment
- 288
- Locations
- 1
- Primary Endpoint
- Geometric Mean Titers (GMTs) of the Serum Anti-RSV Neutralizing Antibody (NAb) Titers
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
Exclusion Criteria
- •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.
Arms & Interventions
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.
Intervention: RSV F subunit 45 μg No adjuvant
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.
Intervention: RSV F subunit 45 μg Aluminum hydroxide adjuvant
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.
Intervention: RSV F subunit 45 μg MF59 adjuvant
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.
Intervention: Placebo
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.
Intervention: RSV F subunit 90 μg No adjuvant
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.
Intervention: RSV F subunit 90 μg Aluminum hydroxide adjuvant
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.
Intervention: RSV F subunit 90 μg MF59 adjuvant
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.
Intervention: Placebo
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.
Intervention: RSV F subunit 135 μg No adjuvant
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.
Intervention: RSV F subunit 135 μg Aluminum hydroxide adjuvant
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.
Intervention: RSV F subunit 135 μg MF59 adjuvant
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.
Intervention: Placebo
Outcomes
Primary Outcomes
Geometric Mean Titers (GMTs) of the Serum Anti-RSV Neutralizing Antibody (NAb) Titers
Time Frame: 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)
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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)
Time Frame: 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.
Secondary Outcomes
- 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)