A Study to Evaluate the Safety and Ability of the Vaccine to Induce Antibodies Against the Respiratory Syncytial Virus in Healthy Adults

NCT02298179 | Completed Phase 1 Results DMC

• 3 other identifiers: 2052192014-000145-69V122_01
• Study Type: interventional
• Target: 288
• Locations: 1 country
• Sites: 1

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.

Conditions

Respiratory Syncytial Virus (RSV)

Keywords

Antibodies; Respiratory syncytial virus; Safety; Healthy adults; Immunogenicity

Outcome Measures

Primary Outcomes (12)

• Geometric Mean Titers (GMTs) of the Serum Anti-RSV Neutralizing Antibody (NAb) Titers

  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).

  At Day 57

• Percentage of Subjects With a ≥ 4-fold Increase in Serum Anti-RSV NAb Titers

  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).

  At Day 57

• Number of Subjects With Any Solicited Local Symptoms

  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.

  Within 30 minutes after each vaccination

• Number of Subjects With Any Solicited Local Symptoms

  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.

  From Day 1 (6 hour) through Day 3 after each vaccination

• Number of Subjects With Any Solicited Local Symptoms

  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.

  From Day 4 through Day 7 after each vaccination

• Number of Subjects With Any Solicited Local Symptoms

  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.

  From Day 1 (6 hours) to Day 7 after each vaccination

• Number of Subjects With Any Solicited Systemic Symptoms and Other Indicators of Reactogenicity

  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.

  Within 30 minutes after each vaccination

• Number of Subjects With Any Solicited Systemic Symptoms and Other Indicators of Reactogenicity

  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.

  From Day 1 (6 hours) through Day 3 after each vaccination

• Number of Subjects With Any Solicited Systemic Symptoms and Other Indicators of Reactogenicity

  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.

  From Day 4 through Day 7 after each vaccination

• Number of Subjects With Any Solicited Systemic Symptoms and Other Indicators of Reactogenicity

  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.

  From Day 1 (6 hours) to Day 7 after each vaccination

• Number of Subjects With Unsolicited Adverse Events (AEs)

  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.

  From Day 1 to Day 28 after each vaccination

• Number of Subjects With Serious Adverse Events (SAEs) and Other Significant AE(s)

  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.

  From study start (Day 1) until study completion (Day 394)

Secondary Outcomes (7)

• 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 a ≥ 4-fold Increase in Serum Anti-RSV NAb Titer

  At Day 29 and at 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

• 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

• 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

Study Arms (12)

RSV F 45 No Adj Group

EXPERIMENTAL

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.

Biological: RSV F subunit 45 μg No adjuvant

RSV F 45 Alum Adj Group

EXPERIMENTAL

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.

Biological: RSV F subunit 45 μg Aluminum hydroxide adjuvant

RSV F 45 MF59 Adj Group

EXPERIMENTAL

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.

Biological: RSV F subunit 45 μg MF59 adjuvant

Placebo 1 Group

PLACEBO COMPARATOR

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.

Drug: Placebo

RSV F 90 No Adj Group

EXPERIMENTAL

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.

Biological: RSV F subunit 90 μg No adjuvant

RSV F 90 Alum Adj Group

EXPERIMENTAL

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.

Biological: RSV F subunit 90 μg Aluminum hydroxide adjuvant

RSV F 90 MF59 Adj Group

EXPERIMENTAL

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.

Biological: RSV F subunit 90 μg MF59 adjuvant

Placebo 2 Group

PLACEBO COMPARATOR

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.

Drug: Placebo

RSV F 135 No Adj Group

EXPERIMENTAL

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.

Biological: RSV F subunit 135 μg No adjuvant

RSV F 135 Alum Adj Group

EXPERIMENTAL

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.

Biological: RSV F subunit 135 μg Aluminum hydroxide adjuvant

RSV F 135 MF59 Adj Group

EXPERIMENTAL

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.

Biological: RSV F subunit 135 μg MF59 adjuvant

Placebo 3 Group

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

RSV F subunit 45 μg No adjuvant BIOLOGICAL

2 doses of 0.5 milliliters (mL) each of injectable solution administered intramuscularly, in the deltoid muscle, preferably in the non-dominant arm.

RSV F 45 No Adj Group

RSV F subunit 45 μg Aluminum hydroxide adjuvant BIOLOGICAL

2 doses of 0.5 milliliters (mL) each of injectable solution administered intramuscularly, in the deltoid muscle, preferably in the non-dominant arm.

RSV F 45 Alum Adj Group

RSV F subunit 45 μg MF59 adjuvant BIOLOGICAL

2 doses of 0.5 milliliters (mL) each of injectable solution administered intramuscularly, in the deltoid muscle, preferably in the non-dominant arm.

RSV F 45 MF59 Adj Group

RSV F subunit 90 μg No adjuvant BIOLOGICAL

2 doses of 0.5 milliliters (mL) each of injectable solution administered intramuscularly, in the deltoid muscle, preferably in the non-dominant arm.

RSV F 90 No Adj Group

RSV F subunit 90 μg Aluminum hydroxide adjuvant BIOLOGICAL

2 doses of 0.5 milliliters (mL) each of injectable solution administered intramuscularly, in the deltoid muscle, preferably in the non-dominant arm.

RSV F 90 Alum Adj Group

RSV F subunit 90 μg MF59 adjuvant BIOLOGICAL

2 doses of 0.5 milliliters (mL) each of injectable solution administered intramuscularly, in the deltoid muscle, preferably in the non-dominant arm.

RSV F 90 MF59 Adj Group

RSV F subunit 135 μg No adjuvant BIOLOGICAL

2 doses of 0.5 milliliters (mL) each of injectable solution administered intramuscularly, in the deltoid muscle, preferably in the non-dominant arm.

RSV F 135 No Adj Group

RSV F subunit 135 μg Aluminum hydroxide adjuvant BIOLOGICAL

2 doses of 0.5 milliliters (mL) each of injectable solution administered intramuscularly, in the deltoid muscle, preferably in the non-dominant arm.

RSV F 135 Alum Adj Group

RSV F subunit 135 μg MF59 adjuvant BIOLOGICAL

2 doses of 0.5 milliliters (mL) each of injectable solution administered intramuscularly, in the deltoid muscle, preferably in the non-dominant arm.

RSV F 135 MF59 Adj Group

Placebo DRUG

2 doses of 0.5 milliliters (mL) each of injectable solution administered intramuscularly, in the deltoid muscle, preferably in the non-dominant arm.

Also known as: Sterile saline 0.9%

Placebo 1 Group; Placebo 2 Group; Placebo 3 Group

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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/m2. 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 0.1.
• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Ghent, 9000, Belgium

Location

Related Publications (2)

• Schneikart G, Tavarini S, Sammicheli C, Torricelli G, Guidotti S, Andreano E, Buricchi F, D'Oro U, Finco O, Bardelli M. The respiratory syncytial virus fusion protein-specific B cell receptor repertoire reshaped by post-fusion subunit vaccination. Vaccine. 2020 Nov 25;38(50):7916-7927. doi: 10.1016/j.vaccine.2020.10.062. Epub 2020 Oct 29.

  PMID: 33131932 DERIVED

• Leroux-Roels G, De Boever F, Maes C, Nguyen TL, Baker S, Gonzalez Lopez A. Safety and immunogenicity of a respiratory syncytial virus fusion glycoprotein F subunit vaccine in healthy adults: Results of a phase 1, randomized, observer-blind, controlled, dosage-escalation study. Vaccine. 2019 May 6;37(20):2694-2703. doi: 10.1016/j.vaccine.2019.04.011. Epub 2019 Apr 12.

  PMID: 30987852 DERIVED

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

kt144805@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2014
• First Posted: November 21, 2014
• Study Start: December 19, 2014
• Primary Completion: March 27, 2017
• Study Completion: March 27, 2017
• Last Updated: August 13, 2018
• Results First Posted: August 13, 2018

Record last verified: 2018-08

Locations

BE (1)