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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT04420221
Ethics application status
Date submitted
4/06/2020
Date registered
9/06/2020
Date last updated
22/09/2021

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 50 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 50 Years of Age With a Recent S. Aureus Skin and Soft Tissue Infection (SSTI)
Secondary ID [1] 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
Other interventions - Sa-5Ag half dose non-adjuvanted
Other interventions - Sa-5Ag full dose non-adjuvanted
Other interventions - Sa-5Ag half dose adjuvanted
Other interventions - Sa-5Ag full dose adjuvanted
Treatment: Drugs - 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 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 5b - 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).


Other interventions: 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.

Other interventions: 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.

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

Other interventions: 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: Drugs: Placebo
One dose of placebo (saline) at Day 1 for placebo groups 1 to 3 and a series of 2 doses of placebo (saline) given approximately 2 months apart (Days 1 and 61) for placebo groups 4 and 5, administered intramuscularly.

Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants with solicited local adverse events (AEs) (any, grade 3) - The solicited local AE(s) assessed are pain, redness and swelling. Any = any solicited local AE, regardless of intensity; Grade 3 pain = Significant pain at rest, that prevents normal every day activities; Grade 3 redness/swelling = greater than or equal to (=)100 mm diameter (greatest surface diameter in millimetres [mm]).
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) - The solicited local AE(s) assessed are pain, redness and swelling. Any = any solicited local AE, regardless of intensity; Grade 3 pain = Significant pain at rest, that prevents normal every day activities; Grade 3 redness/swelling = greater than or equal to (=)100 mm diameter (greatest surface diameter in millimeters [mm]).
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) - The solicited general AE(s) assessed are headache, fatigue, nausea, vomiting, diarrhea, abdominal pain, myalgia, shivering and fever (temperature = 38.0 degrees Celsius (°C)/100.4 degrees Fahrenheit (°F). Any = any solicited general 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.
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) - The solicited general AE(s) assessed are headache, fatigue, nausea, vomiting, diarrhea, abdominal pain, myalgia, shivering and fever (temperature = 38.0 degrees Celsius (°C)/100.4 degrees Fahrenheit (°F). Any = any solicited general 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.
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) - Any (independent from causality) unsolicited AEs regardless of intensity; Grade 3 unsolicited AEs = An AE which prevents normal, everyday activities. Such an AE would, for example, prevent attendance at work/school and would necessitate the administration of corrective therapy. Related unsolicited AEs = AEs assessed by the investigator to be causally related to vaccination. Grade 3 related unsolicited AEs = An AE which prevents normal, everyday activities. Such an AE would, for example, prevent attendance at work/school and would necessitate the administration of corrective therapy.
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) - Any (independent from causality) unsolicited AEs regardless of intensity; Grade 3 unsolicited AEs = An AE which prevents normal, everyday activities. Such an AE would, for example, prevent attendance at work/school and would necessitate the administration of corrective therapy. Related unsolicited AEs = AEs assessed by the investigator to be causally related to vaccination. Grade 3 related unsolicited AEs = An AE which prevents normal, everyday activities. Such an AE would, for example, prevent attendance at work/school and would necessitate the administration of corrective therapy.
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) - Any (independent from causality) SAEs regardless of intensity; Grade 3 SAEs = SAE which prevents normal, everyday activities. Such an SAE would, for example, prevent attendance at work/school and would necessitate the administration of corrective therapy. Related SAEs = SAEs assessed by the investigator to be causally related to vaccination. Grade 3 related SAEs = SAE which prevents normal, everyday activities. Such an SAE would, for example, prevent attendance at work/school and would necessitate the administration of corrective therapy.
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) - Any (independent from causality) SAEs regardless of intensity; Grade 3 SAEs = SAE which prevents normal, everyday activities. Such an SAE would, for example, prevent attendance at work/school and would necessitate the administration of corrective therapy. Related SAEs = SAEs assessed by the investigator to be causally related to vaccination. Grade 3 related SAEs = SAE which prevents normal, everyday activities. Such an SAE would, for example, prevent attendance at work/school and would necessitate the administration of corrective therapy.
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) - Any (independent from causality) PIMDs regardless of intensity; Grade 3 PIMDs = PIMD which prevents normal, everyday activities. Such an PIMD would, for example, prevent attendance at work/school and would necessitate the administration of corrective therapy. Related PIMDs = PIMDs assessed by the investigator to be causally related to vaccination. Grade 3 related PIMDs = PIMD which prevents normal, everyday activities. Such an PIMD would, for example, prevent attendance at work/school and would necessitate the administration of corrective therapy.
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) - Any (independent from causality) PIMDs regardless of intensity; Grade 3 PIMDs = PIMD which prevents normal, everyday activities. Such an PIMD would, for example, prevent attendance at work/school and would necessitate the administration of corrective therapy. Related PIMDs = PIMDs assessed by the investigator to be causally related to vaccination. Grade 3 related PIMDs = PIMD which prevents normal, everyday activities. Such an PIMD would, for example, prevent attendance at work/school and would necessitate the administration of corrective therapy.
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 - The number of participants having hematology and biochemistry results below, within or above the normal laboratory ranges, compared to baseline range indicator.
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 - The number of participants having hematology and biochemistry results below, within or above the normal laboratory ranges, compared to baseline range indicator.
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 - This key secondary outcome measure is to evaluate efficacy in terms of number of participants with at least one culture confirmed case of recurrent S. aureus SSTI starting 14 days after the second dose.
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 - This co-secondary outcome measure is to evaluate efficacy in terms of number of participants with at least one culture confirmed case of recurrent S. aureus SSTI starting 14 days after the first dose.
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 between 18 and 50 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 14 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
50 Years
Gender
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

- 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 2, as determined by physical
examination or laboratory screening tests

- 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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
GSK Investigational Site - Darlinghurst, Sydney
Recruitment hospital [2] 0 0
GSK Investigational Site - Sydney
Recruitment hospital [3] 0 0
GSK Investigational Site - Fortitude Valley
Recruitment hospital [4] 0 0
GSK Investigational Site - Geelong
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst, Sydney
Recruitment postcode(s) [2] 0 0
2010 - Sydney
Recruitment postcode(s) [3] 0 0
4006 - Fortitude Valley
Recruitment postcode(s) [4] 0 0
3220 - Geelong
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Idaho
Country [6] 0 0
United States of America
State/province [6] 0 0
Kentucky
Country [7] 0 0
United States of America
State/province [7] 0 0
Louisiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Michigan
Country [9] 0 0
United States of America
State/province [9] 0 0
Nebraska

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

Ethics approval
Ethics application status

Summary
Brief summary
Safety, immunogenicity and efficacy of GSK S. aureus candidate vaccine (GSK3878858A) when
administered to healthy adults (dose-escalation) and to adults 18 to 50 years of age with a
recent S. aureus skin and soft tissue infection (SSTI). In the dose-escalation safety lead-in
phase in healthy adults safety and immunogenicity of 4 different compositions is assessed.
After safety has been shown in this phase, in the second phase, proof of principle (PoP)
phase of the study in adults with a recent SSTI safety, immunogenicity and efficacy of the
final composition of the vaccine is assessed.
Trial website
https://clinicaltrials.gov/show/NCT04420221
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
US GSK Clinical Trials Call Center
Address 0 0
Country 0 0
Phone 0 0
877-379-3718
Fax 0 0
Email 0 0
GSKClinicalSupportHD@gsk.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04420221