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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04420221




Registration number
NCT04420221
Ethics application status
Date submitted
4/06/2020
Date registered
9/06/2020

Titles & IDs
Public title
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)
Scientific title
A Phase I/II, Observer-blind, Randomised, Placebo-controlled Study to Assess Safety, Immunogenicity and Efficacy of GSK S. Aureus Candidate Vaccine 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)
Secondary ID [1] 0 0
2021-006215-29
Secondary ID [2] 0 0
208833
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Infections, Soft Tissue 0 0
Condition category
Condition code
Infection 0 0 0 0
Studies of infection and infectious agents
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Sexually transmitted infections

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Sa-5Ag half dose non-adjuvanted
Treatment: Other - Sa-5Ag full dose non-adjuvanted
Treatment: Other - Sa-5Ag half dose adjuvanted
Treatment: Other - Sa-5Ag full dose adjuvanted
Treatment: Other - Placebo

Experimental: Half dose non-adj Group 1a - Subjects aged 18 to 50 at the time of first vaccination who receive 1 dose of Sa-5Ag (5 antigens of S. aureus) half dose, non-adjuvanted at Day 1.

Placebo comparator: Placebo Group 1b - Subjects aged 18 to 50 at the time of first vaccination who receive 1 dose of placebo (saline) at Day 1.

Experimental: Full dose non-adj Group 2a - Subjects aged 18 to 50 at the time of first vaccination who receive 1 dose of Sa-5Ag (5 antigens of S. aureus) full dose, non-adjuvanted at Day 1

Placebo comparator: Placebo Group 2b - Subjects aged 18 to 50 at the time of first vaccination who receive 1 dose of placebo (saline) at Day 1.

Experimental: Half dose adj Group 3a - Subjects aged 18 to 50 at the time of first vaccination who receive 1 dose of Sa-5Ag (5 antigens of S. aureus) half dose, adjuvanted at Day 1.

Placebo comparator: Placebo Group 3b - Subjects aged 18 to 50 at the time of first vaccination who receive 1 dose of placebo (saline) at Day 1.

Experimental: Full dose adj Group 4a - Subjects aged 18 to 50 at the time of first vaccination who receive a series of 2 doses of S. aureus candidate vaccine (Sa-5Ag full dose adjuvanted) given approximately 2 months apart (Days 1 and 61)

Placebo comparator: Placebo Group 4b - Subjects aged 18 to 50 at the time of first vaccination who receive a series of 2 doses of placebo (saline) given approximately 2 months apart (Days 1 and 61).

Experimental: Vaccine Group 5a - Subjects aged 18 to 64 at the time of first vaccination who receive a series of 2 doses of S. aureus candidate vaccine (Sa-5Ag full dose adjuvanted) given approximately 2 months apart (Days 1 and 61).

Placebo comparator: Placebo Group 5b - Subjects aged 18 to 64 at the time of first vaccination who receive a series of 2 doses of placebo (saline) given approximately 2 months apart (Days 1 and 61).


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

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

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

Treatment: Other: Sa-5Ag full dose adjuvanted
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.

Treatment: Other: Placebo
One dose of placebo (saline solution for injection/ vial or prefilled syringe) at Day 1 for placebo groups 1 to 3 and a series of 2 doses of placebo given approximately 2 months apart (Days 1 and 61) for placebo groups 4 and 5, administered intramuscularly.
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants with solicited local adverse events (AEs) (any, grade 3)
Timepoint [1] 0 0
During 7 days after the first dose (Days 1 to 8)
Primary outcome [2] 0 0
Number of participants with solicited local adverse events (AEs) (any, grade 3)
Timepoint [2] 0 0
During 7 days after the second dose (Days 61 to 68)
Primary outcome [3] 0 0
Number of participants with solicited general AEs (any, grade 3)
Timepoint [3] 0 0
During 7 days after the first dose (Days 1 to 8)
Primary outcome [4] 0 0
Number of participants with solicited general AEs (any, grade 3)
Timepoint [4] 0 0
During 7 days after the second dose (Days 61 to 68)
Primary outcome [5] 0 0
Number of participants with unsolicited AEs (any, grade 3, related, related grade 3)
Timepoint [5] 0 0
During 30 days after the first dose (Days 1 to 31)
Primary outcome [6] 0 0
Number of participants with unsolicited AEs (any, grade 3, related, related grade 3)
Timepoint [6] 0 0
During 30 days after the second dose (Days 61 to 91)
Primary outcome [7] 0 0
Number of participants with serious AEs (SAEs) (any, grade 3, related, related grade 3)
Timepoint [7] 0 0
Throughout the study period [from Day 1 (day of vaccination) until Day 366
Primary outcome [8] 0 0
Number of participants with serious AEs (SAEs) (any, grade 3, related, related grade 3)
Timepoint [8] 0 0
Throughout the study period [from Day 1 (day of vaccination) until Day 426
Primary outcome [9] 0 0
Number of participants with potential immune-mediated diseases (PIMDs) (any, grade 3, related, related grade 3)
Timepoint [9] 0 0
Throughout the study period [from Day 1 (day of vaccination) until Day 366
Primary outcome [10] 0 0
Number of participants with potential immune-mediated diseases (PIMDs) (any, grade 3, related, related grade 3)
Timepoint [10] 0 0
Throughout the study period [from Day 1 (day of vaccination) until Day 426
Primary outcome [11] 0 0
Number of participants with haematological and biochemical laboratory abnormalities and changes from the baseline values
Timepoint [11] 0 0
At Day 8 (7 days after the first dose)
Primary outcome [12] 0 0
Number of participants with haematological and biochemical laboratory abnormalities and changes from the baseline values
Timepoint [12] 0 0
At Day 68 (7 days after the second dose)
Secondary outcome [1] 0 0
Number of participants with at least one culture confirmed case of recurrent S. aureus SSTI
Timepoint [1] 0 0
Starting from Day 75 (i.e.14 days after the second dose) up to Day 426 (12 months after the second dose).
Secondary outcome [2] 0 0
Number of participants with at least one culture confirmed case of recurrent S. aureus SSTI
Timepoint [2] 0 0
Starting from Day 15 (i.e. 14 days after the first dose) up to Day 426 (12 months after the second dose).

Eligibility
Key inclusion criteria
All subjects must satisfy all the following criteria at study entry:

* Subjects 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 subject prior to performance of any study specific procedure.
* Subject satisfying screening requirements.
* Subjects 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 subjects 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 subjects of childbearing potential may be enrolled in the study, if the subject:
* 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.

Additional inclusion criteria only for subjects to be enrolled in the dose-escalation safety lead-in screening epoch:

- Healthy subjects as established by medical history, clinical examination and laboratory assessment.

Additional inclusion criteria only for subjects to be enrolled in the PoP screening epoch:

- Healthy subjects 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 subjects 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).

OR

- Healthy subjects as established by medical history and clinical examination before entering into the study with an ongoing S. aureus SSTI (i.e. S. aureus is the most likely cause), as confirmed by a S. aureus positive culture performed outside the study procedures and not earlier than 30 days prior to Informed Consent Form signature. Before randomisation subjects have to be treated until clinical resolution of the culture confirmed SSTI caused by S. aureus. These subjects will be enrolled whether they have or have not already started specific treatment of the infection. In case they have not started the treatment, this will be then given in compliance with the standard medical practice for the management of S. aureus SSTIs and the choice and judgment of the most appropriate treatment will be applied by the investigator, outside the study procedures.
Minimum age
18 Years
Maximum age
64 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
All subjects at study entry

* 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.
* Concurrently participating in another clinical study, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product (drug or medical device)
* Received a vaccine against S. aureus
* Pregnant or lactating female
* Female planning to become pregnant or planning to discontinue contraceptive precautions before 2 months after completion of the vaccination series
* History of chronic alcohol consumption and/or drug abuse
* Any study personnel or immediate dependents, family, or household member

All subjects at the time of vaccination

* Any clinically significant hematological (hemoglobin level, white blood cell, lymphocyte, neutrophil, eosinophil, platelet count and red blood cell count) and/or biochemical (alanine aminotransferase [ALT], aspartate aminotransferase [AST], creatinine) laboratory abnormality

Additional exclusion criteria applied only for dose-escalation safety lead-in

* Any active or ongoing illness at screening or time of injection
* History of any serious chronic or progressive disease according to the judgment of the investigator

Additional exclusion criteria applied only for PoP at study entry

* Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination
* Major congenital defects, as assessed by the investigator
* Acute or chronic, clinically significant pulmonary, cardiovascular*, hepatic or renal functional abnormality, neoplasm, diabetes type 1 and uncontrolled diabetes type 2*, as determined by physical examination or laboratory screening tests * Note: Well-controlled type 2 diabetes mellitus (HbA1c <7%) and well-controlled arterial hypertension (blood pressure <140/90 mmHg) can be considered for inclusion in the study.
* Any 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 at risk for severe or life-threatening SSTIs (e.g., lymphatic or venous insufficiency, liver and kidney disease, IV drug use, etc.)
* Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the subject due to participation in the study

Additional exclusion criteria applied only for PoP at vaccination

- Microbiological test results of drainage suggest that the SSTI etiology could be other than infection with S. aureus

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Other
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
29/06/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
14/03/2024
Actual
Sample size
Target
632
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
GSK Investigational Site - Coffs Harbour
Recruitment hospital [2] 0 0
GSK Investigational Site - Darlinghurst, Sydney
Recruitment hospital [3] 0 0
GSK Investigational Site - Sydney
Recruitment hospital [4] 0 0
GSK Investigational Site - Fortitude Valley
Recruitment hospital [5] 0 0
GSK Investigational Site - Southport
Recruitment hospital [6] 0 0
GSK Investigational Site - Geelong
Recruitment postcode(s) [1] 0 0
2450 - Coffs Harbour
Recruitment postcode(s) [2] 0 0
2010 - Darlinghurst, Sydney
Recruitment postcode(s) [3] 0 0
2010 - Sydney
Recruitment postcode(s) [4] 0 0
4006 - Fortitude Valley
Recruitment postcode(s) [5] 0 0
4215 - Southport
Recruitment postcode(s) [6] 0 0
3220 - Geelong
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
Kentucky
Country [4] 0 0
United States of America
State/province [4] 0 0
Louisiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Nebraska
Country [6] 0 0
United States of America
State/province [6] 0 0
North Carolina
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
India
State/province [8] 0 0
Gujarat
Country [9] 0 0
India
State/province [9] 0 0
Maharashtra
Country [10] 0 0
India
State/province [10] 0 0
Uttar Pradesh
Country [11] 0 0
India
State/province [11] 0 0
West Bengal
Country [12] 0 0
India
State/province [12] 0 0
Lucknow
Country [13] 0 0
India
State/province [13] 0 0
Nagpur
Country [14] 0 0
India
State/province [14] 0 0
Pune
Country [15] 0 0
New Zealand
State/province [15] 0 0
Auckland
Country [16] 0 0
New Zealand
State/province [16] 0 0
Christchurch
Country [17] 0 0
New Zealand
State/province [17] 0 0
Nawton
Country [18] 0 0
New Zealand
State/province [18] 0 0
Nelson
Country [19] 0 0
New Zealand
State/province [19] 0 0
New Lynn
Country [20] 0 0
New Zealand
State/province [20] 0 0
Otahuhu
Country [21] 0 0
Poland
State/province [21] 0 0
Bialystok
Country [22] 0 0
Poland
State/province [22] 0 0
Katowice
Country [23] 0 0
Poland
State/province [23] 0 0
Lodz
Country [24] 0 0
Poland
State/province [24] 0 0
Lublin
Country [25] 0 0
Poland
State/province [25] 0 0
Szczecin
Country [26] 0 0
Poland
State/province [26] 0 0
Warszawa
Country [27] 0 0
South Africa
State/province [27] 0 0
Gauteng
Country [28] 0 0
South Africa
State/province [28] 0 0
KwaZulu- Natal
Country [29] 0 0
South Africa
State/province [29] 0 0
Cape Town
Country [30] 0 0
United Kingdom
State/province [30] 0 0
Nottingham
Country [31] 0 0
United Kingdom
State/province [31] 0 0
West Midlands

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKlline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
IPD for this study will be made available via the Clinical Study Data Request site.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
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
Available to whom?
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.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://clinicalstudydatarequest.com


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04420221