SA4Ag Safety, Tolerability, and Immunogenicity Study in Japanese Adults

• ClinicalTrials.gov Identifier: NCT02492958
• Recruitment Status: Completed
• First Posted: July 9, 2015
• Results First Posted: July 30, 2018
• Last Update Posted: July 30, 2018
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: May 29, 2015
• First Posted Date: July 9, 2015
• Results First Submitted Date: August 15, 2017
• Results First Posted Date: July 30, 2018
• Last Update Posted Date: July 30, 2018
• Actual Study Start Date: June 2015
• Actual Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 27, 2018)

• Percentage of Participants With At Least 1 Local Reaction Within 14 Days of Vaccination [ Time Frame: Day 1 up to Day 14 ]
  Local reactions were recorded using an electronic daily diary. Local reactions included redness, swelling and pain at injection site. Redness and swelling were defined as mild (2.5 to 5.0 centimeters [cm]), moderate (5.5 to 10.0 cm) and, severe (greater than or equal to [>=] 10.5 cm). Pain at injection site was defined as mild (did not interfere with activity), moderate (interfered with activity), and severe (prevented daily activity). In this outcome measure percentage of participants with any local reaction was reported.
• Percentage of Participants With Local Reactions by Severity Within 14 Days of Vaccination [ Time Frame: Day 1 up to Day 14 ]
  Local reactions were recorded using an electronic daily diary. Local reactions included redness, swelling and pain at injection site. Redness and swelling were graded as mild (2.5 to 5.0 cm), moderate (5.5 to 10.0 cm) and, severe (>=10.5 cm). Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), and severe (prevented daily activity).
• Percentage of Participants With At Least 1 Systemic Event Within 14 Days of Vaccination [ Time Frame: Day 1 up to Day 14 ]
  Systemic reactions included fever, vomiting, diarrhea, headache, fatigue, muscle and joint pain (other than at the injection site) and recorded by using an e-diary. Fever was graded as 37.5 to 38.4 degree Celsius (C), 38.5 to 38.9 degree C, 39.0 to 40.0 degree C and greater than (>) 40.0 degree C. Vomiting was graded as mild (1-2 times in 24 hours), moderate (>2 times in 24 hours) and severe (required intravenous hydration). Diarrhea was graded as mild (2-3 loose stools in 24 hours), moderate (4-5 loose stools in 24 hours) and severe (>=6 loose stools in 24 hours). Headache, fatigue, muscle pain and joint pain were graded as mild (no interference with activity), moderate (some interference with activity) and severe (significant, prevented daily activity). In this outcome measure percentage of participants with any systemic event was reported.
• Percentage of Participants With Systemic Events by Severity Within 14 Days of Vaccination [ Time Frame: Day 1 up to Day 14 ]
  Systemic reactions included fever, vomiting, diarrhea, headache, fatigue, muscle and joint pain (other than at the injection site) and recorded by using an e-diary. Fever was graded as 37.5 to 38.4 degree C, 38.5 to 38.9 degree C, 39.0 to 40.0 degree C and >40.0 degree C. Vomiting was graded as mild (1-2 times in 24 hours), moderate (>2 times in 24 hours) and severe (required intravenous hydration). Diarrhea was graded as mild (2-3 loose stools in 24 hours), moderate (4-5 loose stools in 24 hours) and severe (>=6 loose stools in 24 hours). Headache, fatigue, muscle pain and joint pain were graded as mild (no interference with activity), moderate (some interference with activity) and severe (significant, prevented daily activity).
• Percentage of Participants With Treatment-Emergent Adverse Events (AEs) Reported From Day 1 Up to Day 29 Visit [ Time Frame: Day 1 up to Day 29 ]
  An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. AEs included both serious and non-serious AEs. Treatment-emergent AEs were events between the administration of investigational product and up to Day 29 that were absent before vaccination or that worsened relative to pre-administration state.
• Percentage of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAE) Reported After Day 29 Visit Through Month 12 [ Time Frame: After Day 29 up to Month 12 ]
  An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly or deemed medically significant for any other reason. A treatment emergent AE was defined as an event that emerged during the study that was absent before administration of investigational product, or worsened relative to the pre-administration state. AEs reported during this time period included both SAEs and newly diagnosed chronic medical disorders (NDCMD). A NDCMD was defined as a disease or medical condition that was not identified prior to study start and was expected to be persistent or otherwise long-lasting in its effects.
• Percentage of Participants With Hematology Abnormalities at Day 5 [ Time Frame: Day 5 ]
  Hematology analysis included the following parameters: hemoglobin, white blood cells, neutrophils and platelets, and scaled as Grade 1= mild; Grade 2= moderate; Grade 3= severe; or Grade 4. Hematology abnormality was defined as at least 1 grade abnormal value. Percentage of participants with abnormal values in hematology parameters are reported in this outcome measure.
• Percentage of Participants With Hematology Abnormalities at Day 15 [ Time Frame: Day 15 ]
  Hematology analysis included the following parameters: hemoglobin, white blood cells, neutrophils and platelets, and scaled as Grade 1= mild; Grade 2= moderate; Grade 3= severe; or Grade 4. Hematology abnormality was defined as at least 1 grade abnormal value. Percentage of participants with abnormal values in hematology parameters are reported in this outcome measure.
• Percentage of Participants With Coagulation Abnormalities at Day 5 [ Time Frame: Day 5 ]
  Coagulation analysis included the following parameters: prothrombin time (PT), activated partial thromboplastin time (APTT), platelet aggregation (AGG) (with adenosine diphosphate [ADP], with arachidonic acid, and with collagen) and fibrinogen activity. PT and APTT were scaled as Grade 1= mild; Grade 2= moderate; Grade 3= severe; or Grade 4. Coagulation abnormality was defined as at least 1 grade abnormal value for PT and APTT, and deviation from local laboratory range for platelet aggregation assay and fibrinogen activity assay. Percentage of participants with abnormal values in coagulation parameters are reported in this outcome measure.
• Percentage of Participants With Coagulation Abnormalities at Day 15 [ Time Frame: Day 15 ]
  Coagulation analysis included the following parameters: PT, APTT, platelet AGG with ADP, platelet AGG with arachidonic acid, platelet AGG with collagen and fibrinogen activity. PT and APTT were scaled as Grade 1= mild; Grade 2= moderate; Grade 3= severe; or Grade 4. Coagulation abnormality was defined as at least 1 grade abnormal value for PT and APTT, and deviation from local laboratory range for platelet aggregation assay and fibrinogen activity assay. Percentage of participants with abnormal values in coagulation parameters are reported in this outcome measure.
• Percentage of Participants With Blood Chemistry Abnormalities at Day 5 [ Time Frame: Day 5 ]
  Blood chemistry laboratory analysis included the following parameters: alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, bilirubin, creatinine, creatine kinase and lactate dehydrogenase, and scaled as Grade 1= mild; Grade 2= moderate; Grade 3= severe; or Grade 4. Blood chemistry abnormality was defined as at least 1 grade abnormal value. Percentage of participants with abnormal values in blood chemistry laboratory parameters are reported in this outcome measure.
• Percentage of Participants With Blood Chemistry Abnormalities at Day 15 [ Time Frame: Day 15 ]
  Blood chemistry laboratory analysis included the following parameters: alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, bilirubin, creatinine, creatine kinase and lactate dehydrogenase, and scaled as Grade 1= mild; Grade 2= moderate; Grade 3= severe; or Grade 4. Blood chemistry abnormality was defined as at least 1 grade abnormal value. Percentage of participants with abnormal values in blood chemistry laboratory parameters are reported in this outcome measure.
• Percentage of Participants Achieving Predefined Antibody Response to Target Antigens at Day 29 [ Time Frame: Day 29 ]
  Percentage of participants achieving predefined antibody response to capsular polysaccharide serotype 5 (CP5), capsular polysaccharide serotype 8 (CP8), clumping factor A (ClfA) and manganese transporter C (MntC) at Day 29 were reported. The predefined thresholds for the target antigens were 1000 and 2000 based on opsonophagocytic activity (OPA) assay for CP5 and CP8, respectively; was 121 based on fibrinogen-binding inhibition (FBI) assay for ClfA and 512 based on competitive Luminex immunoassay (cLIA) for MntC.

Original Primary Outcome Measures (submitted: July 6, 2015)

• Percentage of participants reporting local reactions (size of redness and/or swelling and severity of pain at the injection site) and severity of the local reactions as self-reported on electronic diaries [ Time Frame: 14 days after vaccination ]
• Percentage of participants reporting systemic events (fever, fatigue, headache, vomiting, diarrhea, muscle pain, and joint pain) and severity of systemic events as self-reported on electronic diaries [ Time Frame: 14 days after vaccination ]
• Percentage of participants reporting adverse events, newly diagnosed chronic medical disorders, and serious adverse events categorized according to the Medical Dictionary for Regulatory Activities [ Time Frame: 12 month after vaccination ]
• Percentage of Phase 1 participants with grading shifts in hematology, coagulation, and blood chemistry laboratory assessments [ Time Frame: 15 days after vaccination ]
• Percentage of Phase 1 participants with abnormal hematologic, coagulation, and blood chemistry assessments [ Time Frame: 15 days after vaccination ]
• Percentage of participants achieving antibody responses to specific vaccine components with results ≥ thresholds defined for each vaccine component based on immunoglobulin-binding, opsonophagocytic activity and fibrinogen binding assays. [ Time Frame: 1 month after vaccination ]
  Primary Immunogenicity Endpoints

Current Secondary Outcome Measures (submitted: July 27, 2018)

• Percentage of Participants Achieving Predefined Antibody Response to Target Antigens on Baseline, Day 11, 15 and Month 3 [ Time Frame: Baseline, Day 11, 15 and Month3 ]
  Percentage of participants achieving predefined antibody response to CP5, CP8, ClfA and MntC at Baseline, Day 11, 15 and Month 3 were reported. The predefined thresholds for the target antigens were 1000 and 2000 based on OPA assay for CP5 and CP8, respectively; was 121 based on FBI assay for ClfA, 512 based on cLIA for MntC.
• Antigen-specific Competitive Luminex Immunoassay (cLIA) Geometric Mean Titers (GMTs) [ Time Frame: Baseline, Day 11, 15, 29 and Month 3 ]
  Geometric mean titer is commonly used to assess the immunogenicity of vaccine. Antibody GMTs as measured by cLIA for ClfA and MntC and corresponding 2-sided 95 percent (%) confidence intervals (CIs) were evaluated. CIs were computed by back transforming the CIs generated for means of the titers on the log scale based on the Student t distribution.
• Antigen-specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMTs) [ Time Frame: Baseline, Day 11, 15, 29 and Month 3 ]
  Geometric mean titer is commonly used to assess the immunogenicity of vaccine. Antibody GMTs as measured by OPA for CP5 and CP8 and corresponding 2-sided 95 percent CIs were evaluated. CIs were computed by back transforming the CIs generated for means of the titers on the log scale based on the Student t distribution.
• Antigen-specific Fibrinogen-binding Inhibition (FBI) Assay Geometric Mean Titers (GMTs) [ Time Frame: Baseline, Day 11, 15, 29 and Month 3 ]
  Geometric mean titer is commonly used to assess the immunogenicity of vaccine. Antibody GMTs as measured by FBI for ClfA and corresponding 2-sided 95 percent CIs were evaluated. CIs were computed by back transforming the CIs generated for means of the titers on the log scale based on the Student t distribution.
• Geometric Mean Fold Rise (GMFR) for Staphylococcus Aureus Antigen-specific cLIA Titers From Baseline to Day 11, 15, 29 and Month 3 [ Time Frame: Baseline, Day 11, 15, 29 and Month 3 ]
  GMFRs of anti-Staphylococcus aureus cLIA for ClfA and MntC were computed. CIs which are reported below were computed by back transforming the CIs generated for the mean fold rise on the log scale based on the Student t distribution. GMFRs were computed as the fold rise in titer value at specified time point compared to baseline.
• Geometric Mean Fold Rise (GMFR) for Staphylococcus Aureus Antigen-specific OPA Titers From Baseline to Day 11, 15, 29 and Month 3 [ Time Frame: Baseline, Day 11, 15, 29 and Month 3 ]
  GMFRs of anti-Staphylococcus aureus OPA for CP5 and CP8 were computed. CIs which are reported below were computed by back transforming the CIs generated for the mean fold rise on the log scale based on the Student t distribution. GMFRs were computed as the fold rise in titer value at specified time point compared to baseline.
• Geometric Mean Fold Rise (GMFR) for Staphylococcus Aureus Antigen-specific FBI Titers From Baseline to Day 11, 15, 29 and Month 3 [ Time Frame: Baseline, Day 11, 15, 29 and Month 3 ]
  GMFR of anti-Staphylococcus aureus FBI for ClfA was computed. CIs which are reported below were computed by back transforming the CIs generated for the mean fold rise on the log scale based on the Student t distribution. GMFRs were computed as the fold rise in titer value at specified time point compared to baseline.

Original Secondary Outcome Measures (submitted: July 6, 2015)

• Geometric mean titers specific to each vaccine component at each applicable blood sampling time pointe based on immunoglobulin-binding, opsonophagocytic activity and fibrinogen binding assays. [ Time Frame: various, up to 3 months ]
• Geometric mean fold rise specific to each vaccine component at each applicable blood sampling time pointe based on immunoglobulin-binding, opsonophagocytic activity and fibrinogen binding assays. [ Time Frame: various, up to 3 months ]
• Percentage of participants achieving antibody responses to specific vaccine components with results ≥ thresholds defined for each vaccine component based on immunoglobulin-binding, opsonophagocytic activity and fibrinogen binding assays. [ Time Frame: various, up to 3 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: SA4Ag Safety, Tolerability, and Immunogenicity Study in Japanese Adults
• Official Title: A Phase 1/2a Placebo-controlled, Randomized, Double-blind, Sponsor-unblinded Trial To Evaluate The Safety, Tolerability, And Immunogenicity Of Staphylococcus Aureus 4-antigen Vaccine (sa4ag) In Japanese Adults
• Brief Summary: The purpose of this study is to evaluate the safety, tolerability, and immunogenicity of a single dose of Staphylococcus aureus 4 antigen vaccine in Japanese adults aged 20 to <86 years.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Other
• Condition: Staphylococcal Infections

Intervention

• Biological: Staphylococcus aureus 4-antigen vaccine
  a single 0.5 mL dose of investigational product into the deltoid muscle in the upper arm
  Other Name: SA4Ag
• Biological: Placebo
  a single 0.5 mL dose of investigational product into the deltoid muscle in the upper arm

Study Arms

• Experimental: SA4Ag
  Staphylococcus aureus 4-antigen vaccine
  Intervention: Biological: Staphylococcus aureus 4-antigen vaccine
• Placebo Comparator: Placebo
  a lyophile match to the vaccine, consisting of excipients of SA4Ag formulation minus the active ingredients
  Intervention: Biological: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 6, 2015): 136
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: September 2016
• Actual Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Japanese male and female adults aged 20 to <86 years,
2. Determined as healthy by the investigator (Subjects with preexisting chronic medical conditions determined to be stable may be included),
3. Must be available for the 12 month duration of the study,
4. Subjects must agree to use an acceptable method of birth control for 3 months after study vaccination (if the subject or the subject's partner are/is capable of having children).

Exclusion Criteria:

1. Any contraindication to vaccination or vaccine components, including previous anaphylactic reaction to any vaccine or vaccine-related components,
2. Unstable or serious chronic medical condition that would increase the subject's risk of participation,
3. Immune system suppression or treatment with medications that suppress the immune system,
4. Receipt of blood products or immunoglobulins within the past 12 months,
5. Any infection proven or suspected to be caused by S.aureus within the past 6 months,
6. A staff member at this site nor a relative of those site staff members, nor a sponsor's employee directly involved in the conduct of this research study,
7. Living in a nursing home, long-term care facility or other institution or requiring any types of nursing care,
8. A pregnant or a breast feeding woman.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan

Administrative Information

• NCT Number: NCT02492958
• Other Study ID Numbers: B3451003; 6123K1-1006 ( Other Identifier: Alias Study Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Pfizer
• Original Responsible Party: Same as current
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: July 2018