Safety, Immunogenicity and Efficacy of GSK S. Aureus Candidate Vaccine (GSK3878858A) When Administered to Healthy Adults (Dose-escalation) and to Adults 18 to 64 Years of Age With a Recent S. Aureus Skin and Soft Tissue Infection (SSTI)

NCT04420221 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2088332021-006215-29
• Study Type: interventional
• Target: 226
• Locations: 0 countries
• Sites: N/A

Brief Summary

The study evaluates the safety, immunogenicity, and efficacy of the GSK S. aureus candidate vaccine (GSK3878858A) when administered to two groups: healthy adults (dose-escalation phase) and adults aged 18 to 64 years with a recent S. aureus skin and soft tissue infection (SSTI). In the dose-escalation safety lead-in phase, the safety and immunogenicity of four different vaccine compositions are assessed in healthy adults. Once safety has been established in this phase, the second phase, known as the proof of principle (PoP) phase, will assess the safety, immunogenicity, and efficacy of the final vaccine composition in adults with a recent SSTI.

Conditions

Infections, Soft Tissue

Keywords

S. aureus; skin and soft tissue infection; first time in human; S. aureus vaccine

Outcome Measures

Primary Outcomes (16)

• Dose-escalation Safety lead-in: Number of Participants With Any and Grade 3 Solicited Administration Site Adverse Events (AEs) After Each Vaccination

  The solicited administration site AE(s) assessed are pain, redness and swelling. Any = any solicited administration site AE, regardless of intensity; Grade 3 Pain at injection site = Severe, significant pain at rest, that prevents normal everyday activities; Grade 3 redness/swelling = greater than (\>)100 millimeter (mm) diameter.

  Within 7 days post vaccination (day of administration and 6 subsequent days post-each vaccination; Vaccination 1 on Day 1 and Vaccination 2 on Day 61)

• PoP: Number of Participants With Any and Grade 3 Solicited Administration Site AEs After Each Vaccination

  The solicited administration site AEs assessed are pain, redness and swelling. Any = any solicited administration site AE, regardless of intensity; Grade 3 Pain at injection site = Severe, significant pain at rest, that prevents normal everyday activities; Grade 3 redness/swelling = greater than (\>)100 millimeter (mm) diameter.

  Within 7 days post vaccination (day of administration and 6 subsequent days post-each vaccination; Vaccination 1 on Day 1 and Vaccination 2 on Day 61)

• Dose-escalation Safety lead-in: Number of Participants With Any and Grade 3 Solicited Systemic AEs After Each Vaccination

  The solicited systemic AE(s) assessed are headache, fatigue, nausea, vomiting, diarrhea, abdominal pain, myalgia, shivering and fever. Any = any solicited systemic AE regardless of intensity; Grade 3 headache/fatigue/nausea/abdominal pain/myalgia/shivering = Severe: Prevents daily activity. Grade 3 vomiting = Severe: 6 or more times in 24 hours or requires intravenous hydration. Grade 3 diarrhea = Severe: 6 or more loose stools in 24 hours or requires intravenous hydration. Grade 3 fever = body temperature greater than (\>) 40.0°C/104°F.

  Within 7 days post vaccination (day of administration and 6 subsequent days post-each vaccination; Vaccination 1 on Day 1 and Vaccination 2 on Day 61)

• PoP: Number of Participants With Any and Grade 3 Solicited Systemic AEs After Each Vaccination

  The solicited systemic AE(s) assessed are headache, fatigue, nausea, vomiting, diarrhea, abdominal pain, myalgia, shivering and fever were assessed. Any = any solicited systemic AE regardless of intensity; Grade 3 headache/fatigue/nausea/abdominal pain/myalgia/shivering = Severe: Prevents daily activity. Grade 3 vomiting = Severe: 6 or more times in 24 hours or requires intravenous hydration. Grade 3 diarrhea = Severe: 6 or more loose stools in 24 hours or requires intravenous hydration. Grade 3 fever = body temperature greater than (\>) 40.0°C/104°F.

  Within 7 days post vaccination (day of administration and 6 subsequent days post-each vaccination; Vaccination 1 on Day 1 and Vaccination 2 on Day 61)

• Dose-escalation Safety lead-in: Number of Participants With Unsolicited AEs (Any, Grade 3, Related, Related Grade 3) After Each Vaccination

  An unsolicited adverse event is defined as an adverse event that was not solicited using a Subject Diary and that was spontaneously communicated by a subject who has signed the informed consent. Any unsolicited AE, Grade 3 unsolicited AE, unsolicited AE causally related to the vaccination and Grade 3 unsolicited AE causally related to the vaccination were assessed. A grade 3 AE is an AE that prevents normal, everyday activities.

  During 30 days after each vaccination (day of administration and 29 subsequent days post-each vaccination; Vaccination 1 on Day 1 and Vaccination 2 on Day 61)

• PoP: Number of Participants With Unsolicited AEs (Any, Grade 3, Related, Related Grade 3) After Each Vaccination

  An unsolicited adverse event is defined as an adverse event that was not solicited using a Subject Diary and that was spontaneously communicated by a subject who has signed the informed consent. Any unsolicited AE, Grade 3 unsolicited AE, unsolicited AE causally related to the vaccination and Grade 3 unsolicited AE causally related to the vaccination were assessed. A grade 3 AE is an AE that prevents normal, everyday activities.

  During 30 days after each vaccination (day of administration and 29 subsequent days post-each vaccination; Vaccination 1 on Day 1 and Vaccination 2 on Day 61)

• Dose-escalation Safety lead-in: Number of Participants With Serious AEs (SAEs) up to 1 Year Post First Vaccination

  A SAE is defined as any untoward medical occurrence that, at any dose: resulted in death, was life threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment. A grade 3 SAE is a SAE that prevents normal, everyday activities.

  From Day 1 to Day 366

• Dose-escalation Safety lead-in: Number of Participants With SAEs up to 1 Year Post Second Vaccination

  A SAE is defined as any untoward medical occurrence that, at any dose: resulted in death, was life threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment. A grade 3 SAE is a SAE that prevents normal, everyday activities.

  From Day 61 to Day 426 (post vaccination at Day 61)

• PoP: Number of Participants With SAEs

  A SAE is defined as any untoward medical occurrence that, at any dose: resulted in death, was life threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment. A grade 3 SAE is a SAE that prevents normal, everyday activities.

  From Day 1 to Day 426

• Dose-escalation Safety lead-in: Number of Participants With Potential Immune-mediated Diseases (pIMDs) up to 1 Year Post First Vaccination

  pIMDs are defined as a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology.

  From Day 1 to Day 366

• Dose-escalation Safety lead-in: Number of Participants With pIMDs up to 1 Year Post Second Vaccination

  pIMDs are defined as a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology.

  From Day 61 to Day 426 (post vaccination at Day 61)

• PoP: Number of Participants With Potential Immune-mediated Diseases (pIMDs)

  pIMDs are defined as a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology.

  From Day 1 to Day 426

• Number of Participants With Maximum Toxicity Grade Increase From Baseline for Haematological and Biochemical Laboratory Parameters

  The Biochemical parameters assessed were: Creatinine, Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and the Haematological parameters assessed were: Haemoglobin, white blood cells (WBC) decrease, WBC increase, Neutrophils decrease, Platelets decrease, Lymphocytes decrease, Eosinophils increase. Hematological and biochemical laboratory results are defined as follows: \<parameter\>,\<grade at baseline\>,\<grade at visit\> (e.g. ALT, Grade 0, Grade 0), where Grade 0 = a non-missing parameter value for which grade could not be derived according to the grading scale and does not belong to Grade 1-4; Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life-Threatening. Grading following the FDA Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (September 2007). Unknown = parameter value missing for the specified parameter.

  On Day 8 compared to Baseline (Day 1)

• Number of Participants With Maximum Toxicity Grade Increase From Baseline for Haematological and Biochemical Laboratory Parameters

  The Biochemical parameters assessed were: Creatinine, AST, ALT and the Haematological parameters assessed were: Haemoglobin, WBC decrease, WBC increase, Neutrophils decrease, Platelets decrease, Lymphocytes decrease, Eosinophils increase. Hematological and biochemical laboratory results are defined as follows: \<parameter\>,\<grade at baseline\>,\<grade at visit\> (e.g. ALT, Grade 0, Grade 0), where Grade 0 = a non-missing parameter value for which grade could not be derived according to the grading scale and does not belong to Grade 1-4; Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life-Threatening. Grading following the FDA Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (September 2007). Unknown = parameter value missing for the specified parameter.

  On Day 68 compared to Baseline (Day 61)

• Number of Participants With Haematological and Biochemical Laboratory Change From Baseline Values

  The Biochemical parameters assessed were: Creatinine, AST, ALT and the Haematological parameters assessed were: Haemoglobin, WBC decrease, WBC increase, Neutrophils decrease, Platelets decrease, Lymphocytes decrease, Eosinophils increase. Hematological and biochemical laboratory results are defined as follows: \<parameter\>,\<any grade at baseline\>,\<grade at visit\> (e.g. ALT, Any, Grade 0), where Grade 0 = a non-missing parameter value for which grade could not be derived according to the grading scale and does not belong to Grade 1-4; Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life-Threatening. Grading following the FDA Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (September 2007). Unknown = parameter value missing for the specified parameter.

  On Day 8

• Number of Participants With Haematological and Biochemical Laboratory Change From Baseline Values

  The Biochemical parameters assessed were: Creatinine, AST, ALT and the Haematological parameters assessed were: Haemoglobin, WBC decrease, WBC increase, Neutrophils decrease, Platelets decrease, Lymphocytes decrease, Eosinophils increase. Hematological and biochemical laboratory results are defined as follows: \<parameter\>,\<any grade at baseline\>,\<grade at visit\> (e.g. ALT, Any, Grade 0), where Grade 0 = a non-missing parameter value for which grade could not be derived according to the grading scale and does not belong to Grade 1-4; Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life-Threatening. Grading following the FDA Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (September 2007). Unknown = parameter value missing for the specified parameter.

  On Day 68

Secondary Outcomes (3)

• Number of Participants With at Least One Culture Confirmed Case of Recurrent Staphylococcus Aureus (S. Aureus) Skin and Soft Tissue Infection (SSTI) - Interim Analysis

  From Day 75 to Day 426

• Number of Participants With at Least One Culture Confirmed Case of Recurrent S. Aureus SSTI - Final Analysis

  From Day 75 to Day 426

• Number of Participants With at Least One Culture Confirmed Case of Recurrent S. Aureus SSTI - Final Analysis

  From Day 15 to Day 426

Study Arms (7)

Group 1 Dose-escalation Safety Lead-in Epoch: Half dose Non-Adjuvant (Non-Adj)

EXPERIMENTAL

Participants received 1 dose of the half dose formulation of the vaccine on Day 1.

Biological: Sa-5Ag half dose non-adjuvanted

Group 2 Dose-escalation Safety Lead-in Epoch: Full dose Non-Adj

EXPERIMENTAL

Participants received 1 dose of the full dose formulation of the vaccine on Day 1.

Biological: Sa-5Ag full dose non-adjuvanted

Group 3 Dose-escalation Safety Lead-in Epoch: Half dose Adj

EXPERIMENTAL

Participants received 1 dose of the half dose formulation of the vaccine with adjuvant on Day 1.

Biological: Sa-5Ag half dose adjuvanted

Group 4 Dose-escalation Safety Lead-in Epoch: Full dose Adj

EXPERIMENTAL

Participants received 2 doses of the full dose formulation of the vaccine with adjuvant on Day 1 and Day 61.

Biological: Sa-5Ag full dose adjuvanted

Dose-escalation Safety Lead-in Epoch: Placebo

PLACEBO COMPARATOR

Participants received matching placebo on Day 1 for Group 1, Group 2 and Group 3, and on Day 1 and Day 61 for Group 4 of the escalation epoch.

Biological: Placebo

Proof of Principle (PoP): Full dose Adj

EXPERIMENTAL

Participants were randomized to receive 2 doses of the full dose formulation of the vaccine with adjuvant on Day 1 and Day 61.

Biological: Sa-5Ag full dose adjuvanted

PoP: Placebo

PLACEBO COMPARATOR

Participants were randomized to receive 2 doses of placebo on Day 1 and Day 61.

Biological: Placebo

Interventions

Sa-5Ag half dose non-adjuvanted BIOLOGICAL

1 dose of Sa-5Ag (5 antigens of S. aureus) half dose, non-adjuvanted at Day 1, administered intramuscularly.

Group 1 Dose-escalation Safety Lead-in Epoch: Half dose Non-Adjuvant (Non-Adj)

Sa-5Ag full dose non-adjuvanted BIOLOGICAL

1 dose of Sa-5Ag (5 antigens of S. aureus) full dose, non-adjuvanted at Day 1, administered intramuscularly.

Group 2 Dose-escalation Safety Lead-in Epoch: Full dose Non-Adj

Sa-5Ag half dose adjuvanted BIOLOGICAL

1 dose of Sa-5Ag (5 antigens of S. aureus) half dose, adjuvanted at Day 1, administered intramuscularly.

Group 3 Dose-escalation Safety Lead-in Epoch: Half dose Adj

Sa-5Ag full dose adjuvanted BIOLOGICAL

A series of 2 doses of S. aureus candidate vaccine (Sa-5Ag full dose adjuvanted) given approximately 2 months apart (Days 1 and 61), administered intramuscularly.

Group 4 Dose-escalation Safety Lead-in Epoch: Full dose Adj; Proof of Principle (PoP): Full dose Adj

Placebo BIOLOGICAL

One dose of placebo (saline solution for injection/ vial or prefilled syringe) at Day 1 for placebo Groups 1 to 3 (Dose-escalation epoch) and a series of 2 doses of placebo given approximately 2 months apart (Days 1 and 61) for placebo Group 4 (Dose-escalation epoch) and Group PoP: Placebo, administered intramuscularly.

Dose-escalation Safety Lead-in Epoch: Placebo; PoP: Placebo

Eligibility Criteria

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

You may qualify if:

• All participants must satisfy all the following criteria at study entry:
• Participants who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visits).
• Written or witnessed informed consent obtained from the participant prior to performance of any study specific procedure.
• Participant satisfying screening requirements.
• Participants who, after the nature of the study has been explained to them, have shown adequate comprehension of the study procedures and knowledge of study.
• A male or female
• Dose escalation and safety lead-in phase: Aged between 18 and 50 years of age, inclusive, at the time of first vaccination.
• PoP phase: Aged between 18 and 64 years of age, inclusive, at the time of first vaccination.
• Female participants of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as pre-menarche, current bilateral tubal ligation or occlusion, hysterectomy, bilateral ovariectomy or post-menopause.
• Female participants of childbearing potential may be enrolled in the study, if the participant:
• has practiced adequate contraception for 30 days prior to vaccination,
• has a negative pregnancy test on the day of enrolment, and
• has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series.
• \- Healthy participants as established by medical history, clinical examination and laboratory assessment.
• \- Healthy participants as established by medical history and clinical examination before entering into the study with an ongoing SSTI suspected to be caused by S. aureus, as diagnosed by investigator (before randomization participants have to be treated until clinical resolution of culture confirmed SSTI caused by S. aureus). SSTI must be amenable to microbiological culturing per standard clinical practice (i.e. recovery of drainage sample from abscess or suppurative cellulitis).

You may not qualify if:

• All participants at study entry
• Body mass index (BMI) \>40 kg/m2
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine
• Hypersensitivity to latex
• Recurrent history of uncontrolled neurological disorders or seizures
• History of potential immune-mediated disease (pIMD)
• Clinical conditions that in the investigator's opinion represent a contraindication to intramuscular vaccination and blood draws
• Known bleeding diathesis or any condition that may be associated with a prolonged bleeding time
• Use of any investigational or non-registered product (drug, vaccine or medical device) other than the study vaccine(s) within 30 days before the first dose of study vaccine(s)/placebo (Day -29 to Day 1), or during the study period
• Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting 3 months prior to the first vaccine/placebo dose
• Cytotoxic therapy (e.g., medications used during cancer chemotherapy)
• Administration of long-acting immune-modifying drugs at any time during the study period (e.g. infliximab)
• Administration of immunoglobulins and/or any blood products or plasma derivatives within 3 months before the first dose of study vaccine or during the study period
• Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 15 days before the first dose and ending 15 days after the last dose of vaccine(s) administration with the exception of any non-adjuvanted influenza vaccine which may be administered ≥7 days before or after each study vaccination
• \*In case an emergency mass vaccination for an unforeseen public health threat (e.g.: a pandemic) is organised by the public health authorities, outside the routine immunisation program, the time period described above can be reduced if necessary for that vaccine provided it is licensed and used according to its Product Information.

Sponsors & Collaborators

• GlaxoSmithKline: lead

MeSH Terms

Conditions

Soft Tissue Infections; Staphylococcal Infections

Condition Hierarchy (Ancestors)

Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKlline

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2020
• First Posted: June 9, 2020
• Study Start: November 16, 2022
• Primary Completion: March 12, 2024
• Study Completion: March 12, 2024
• Last Updated: May 8, 2025
• Results First Posted: May 8, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.