Extension Study to Evaluate the Immunogenicity and Safety of the Second Dose of GBS Trivalent Vaccine in Healthy Non-Pregnant Subjects.

Streptococcus Agalactiae Clinical Trial

Official title:

A Phase 2, Non-Randomized, Controlled, Open-Label, Parallel-Group, Extension Study to Evaluate the Immunogenicity and Safety of the Second Dose of GBS Trivalent Vaccine in Healthy Non-pregnant Subjects.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02690181
• Other study ID #: 205421
• Secondary ID: 2015-003094-15V9
• Status: Completed
• Phase: Phase 2
• Start date: March 29, 2016
• Est. completion date: November 2, 2016

Study information

• Verified date: March 2024
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objective of this extension study is the initial assessment of safety and immunogenicity of the second dose of GBS Trivalent Vaccine following the time interval that is close to the inter-pregnancy interval observed in the general population.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: November 2, 2016
• Est. primary completion date: November 2, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 22 Years to 46 Years

Eligibility

Inclusion Criteria:

1. Healthy, non-pregnant subjects who have received a single 5 µg dose of GBS Trivalent Vaccine or placebo in the V98_06 study and healthy non-pregnant female subjects aged 22-46 years inclusive on the day of informed consent who have not received any GBS vaccine in the past

2. Individuals in good health as determined by the outcome of medical history, physical examination and clinical judgment of the investigator

3. Females of childbearing potential who are using an effective birth control method which they intend to use until the end of the study (day 181 visit) or females of non-childbearing potential

Exclusion Criteria:

1. Progressive, unstable or uncontrolled clinical conditions, or clinical conditions representing a contraindication to intramuscular vaccination and blood draws

2. Abnormal function of the immune system

3. Received immunoglobulins or any blood products within 180 days prior to informed consent

4. Received an investigational or non-registered medicinal product within 30 days prior to informed consent

5. Any other clinical condition that, in the opinion of the investigator, might interfere with the results of the study or pose additional risk to the subject due to participation in the study

6. Individuals who received any other vaccines within 14 days for inactivated vaccines or 28 days for live vaccines prior to enrolment in this study or who are planning to receive any vaccine within 28 days from the study vaccination. Exception - an inactivated influenza vaccine may be administered up to 7 days prior to study vaccination or 7 days after study vaccination

7. Individuals who anticipate becoming pregnant prior to the end of the study, or individuals who are breastfeeding

8. Individuals who have had a previous immunization with a vaccine containing Group B Streptococcus antigens that was not part of V98_06 study

9. Individuals with a fever (oral temperature = 38°C) within 3 days prior to day 1 or use of antipyretics and/or analgesic medications within 24 hours prior to day 1

10. Individuals with acute or chronic infection(s) that require systemic antibiotic treatment or antiviral therapy, within 7 days prior to day 1

Related Conditions & MeSH terms

• Bacterial Infection Due to Streptococcus, Group B
• Bacterial Infections
• Streptococcus Agalactiae

Intervention

Biological:
• GBS Trivalent Vaccine
Administration of lyophilized formulation of a GBS trivalent vaccine containing 5 µg of each polysaccharide capsules from serotypes Ia, Ib, and III of Group B Streptococcus conjugated to CRM-197 .

Locations

Country	Name	City	State
Belgium	GSK Investigational Site	Ghent

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

Belgium, 

References & Publications (1)

Leroux-Roels G, Bebia Z, Maes C, Aerssens A, De Boever F, Grassano L, Buffi G, Margarit I, Karsten A, Cho S, Slobod K, Corsaro B, Henry O. Safety and Immunogenicity of a Second Dose of an Investigational Maternal Trivalent Group B Streptococcus Vaccine in Nonpregnant Women 4-6 Years After a First Dose: Results From a Phase 2 Trial. Clin Infect Dis. 2020 Jun 10;70(12):2570-2579. doi: 10.1093/cid/ciz737. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Subjects With ELISA Antibody Concentrations of GBS Serotype Ia Above Pre-specified Thresholds - Day 61	Percentage of subjects who reach pre-defined sequential serotype-specific serum antibody levels for serotype Ia at Day 61 post-vaccination, as measured by Enzyme-linked immunosorbent Assay (ELISA).	At Day 61
Primary	Percentage of Subjects With Antibody Concentrations of GBS Serotype Ib Above Pre-specified Thresholds - Day 61	Percentage of subjects who reach pre-defined sequential serotype-specific serum antibody levels for serotype Ib at day 61 post-vaccination. As the singleton ELISA was no longer in use at the time of serotypes Ib and III testing, results for both serotypes were tested using multiplex immunoassay.	At Day 61
Primary	Percentage of All Subjects With Antibody Concentrations of GBS Serotype III Above Pre-specified Thresholds - Day 61	Percentage of subjects who reach pre-defined sequential serotype-specific serum antibody levels for serotype III at day 61 post-vaccination. As the singleton ELISA was no longer in use at the time of serotypes Ib and III testing, results for both serotypes were tested using multiplex immunoassay.	At Day 61
Primary	Numbers of Subjects With Solicited Local and Systemic Adverse Events (AEs)	Threshold for Erythema, Swelling and Induration: None (0 mm), Any (>= 1 mm).	Day 1 to Day 7
Primary	Number of Subjects With Any Unsolicited Adverse Events (AEs)	The number of subjects with any unsolicited AEs from the day of vaccination in study V98_06E1 to Day 31. An unsolicited adverse event is 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. Potential unsolicited AEs may be medically attended (defined as symptoms or illnesses requiring hospitalization, or emergency room visit, or visit to/by a health care provider), or were of concern to the subject. Possibly Related AE definition: the administration of the investigational vaccine and AE are considered reasonably related in time and the AE could be explained by exposure to the investigational vaccine or by other causes. Probably Related AE definition: exposure to the investigational vaccine and AE are reasonably related in time and no alternative explanation has been identified.	Day 1 to Day 31
Primary	Number of Subjects With Serious Adverse Events (SAEs), Medically Attended AEs, and AEs Leading to Study Withdrawal	An SAE is defined as any untoward medical occurrence that at any dose results in one or more of the following: Death; life-threatening; that does not refer to an event which hypothetically might have caused death if it were more severe; required or prolonged hospitalization; persistent or significant disability/incapacity; congenital anomaly/or birth defect; any important and significant medical event that may not be immediately life-threatening or resulting in death or hospitalization but, based upon appropriate medical judgement, may jeopardize the subject or may require intervention to prevent one of the other outcomes listed above. "Medically attended adverse event" is defined as an adverse event that leads to a visit to a healthcare provider and "AEs leading to withdrawal" are defined as adverse events leading to study or vaccine withdrawal.	Day 1 to Day 181
Secondary	Percentage of Subjects With ELISA Antibody Concentrations of GBS Serotype Ia Above Pre-specified Thresholds - Day 31	Percentage of subjects who reach pre-defined sequential serotype-specific serum antibody levels for serotype Ia at Day 31 post-vaccination, as measured by ELISA.	At Day 31
Secondary	Percentage of Subjects With Antibody Concentrations of GBS Serotype Ib Above Pre-specified Thresholds - Day 31	Percentage of subjects who reach pre-defined sequential serotype-specific serum antibody levels for serotype Ib at day 31 post-vaccination. As the singleton ELISA was no longer in use at the time of serotypes Ib and III testing, results for both serotypes were tested using multiplex immunoassay.	At Day 31
Secondary	Percentage of Subjects With Antibody Concentrations of GBS Serotype III Above Pre-specified Thresholds - Day 31	Percentage of subjects who reach pre-defined sequential serotype-specific serum antibody levels for serotype III at day 31 post-vaccination. As the singleton ELISA was no longer in use at the time of serotypes Ib and III testing, results for both serotypes were tested using multiplex immunoassay.	At Day 31
Secondary	Geometric Mean ELISA Antibody Concentrations of GBS Serotype Ia	The Geometric Mean ELISA Antibody Concentrations of GBS Serotype Ia in All Subjects were estimated for at Day 1, Day 31 and Day 61.	At Day 1, Day 31 and Day 61.
Secondary	Geometric Mean Antibody Concentrations of GBS Serotype Ib	The Geometric Mean Antibody Concentrations of GBS Serotype Ib in All Subjects were estimated for at Day 1, Day 31 and Day 61. As the singleton ELISA was no longer in use at the time of serotypes Ib and III testing, results for both serotypes were tested using multiplex immunoassay.	At Day 1, Day 31 and Day 61
Secondary	Geometric Mean Antibody Concentrations of GBS Serotype III	The Geometric Mean Antibody Concentrations of GBS Serotype III in All Subjects were estimated for at Day 1, Day 31 and Day 61. As the singleton ELISA was no longer in use at the time of serotypes Ib and III testing, results for both serotypes were tested using multiplex immunoassay.	At Day 1, Day 31 and Day 61
Secondary	Geometric Mean ELISA Antibody Concentrations of GBS Serotype Ia in Subjects With Prevaccination Serotype-specific GBS Antibody Less Than the Lower Limit of Quantitation (LLQ)	The Geometric Mean ELISA Antibody Concentrations of GBS Serotype Ia in subjects with prevaccination serotype-specific GBS antibody less than LLQ were estimated for at Day 1, Day 31 and Day 61.	At Day 1, Day 31 and Day 61
Secondary	Geometric Mean Antibody Concentrations of GBS Serotype Ib in Subjects With Prevaccination Serotype-specific GBS Antibody Less Than LLQ	The Geometric Mean Antibody Concentrations of GBS Serotype Ib in subjects with prevaccination serotype-specific GBS antibody less than LLQ were estimated for at Day 1, Day 31 and Day 61. As the singleton ELISA was no longer in use at the time of serotypes Ib and III testing, results for both serotypes were tested using multiplex immunoassay.	At Day 1, Day 31 and Day 61
Secondary	Geometric Mean Antibody Concentrations of GBS Serotype III in Subjects With Prevaccination Serotype-specific GBS Antibody Less Than LLQ	The Geometric Mean Antibody Concentrations of GBS Serotype III in subjects with prevaccination serotype-specific GBS antibody less than LLQ were estimated for at Day 1, Day 31 and Day 61. As the singleton ELISA was no longer in use at the time of serotypes Ib and III testing, results for both serotypes were tested using multiplex immunoassay.	At Day 1, Day 31 and Day 61
Secondary	Geometric Mean ELISA Antibody Concentrations of GBS Serotype Ia in Subjects With Prevaccination Serotype-specific GBS Antibody Equal or Greater Than LLQ	The Geometric Mean ELISA Antibody Concentrations of GBS Serotype Ia in subjects with prevaccination serotype-specific GBS antibody equal or greater than LLQ were estimated for at Day 1, Day 31 and Day 61.	At Day 1, Day 31 and Day 61
Secondary	Geometric Mean Antibody Concentrations of GBS Serotype Ib in Subjects With Prevaccination Serotype-specific GBS Antibody Equal or Greater Than LLQ	The Geometric Mean Antibody Concentrations of GBS Serotype Ib in subjects with prevaccination serotype-specific GBS antibody equal or greater than LLQ were estimated for at Day 1, Day 31 and Day 61. As the singleton ELISA was no longer in use at the time of serotypes Ib and III testing, results for both serotypes were tested using multiplex immunoassay.	At Day 1, Day 31 and Day 61
Secondary	Geometric Mean Antibody Concentrations of GBS Serotype III in Subjects With Prevaccination Serotype-specific GBS Antibody Equal or Greater Than LLQ	The Geometric Mean Antibody Concentrations of GBS Serotype III in subjects with prevaccination serotype-specific GBS antibody equal or greater than LLQ were estimated for at Day 1, Day 31 and Day 61. As the singleton ELISA was no longer in use at the time of serotypes Ib and III testing, results for both serotypes were tested using multiplex immunoassay.	At Day 1, Day 31 and Day 61
Secondary	Geometric Mean ELISA Anti-Diphtheria Antibody Concentrations in All Subjects	Geometric Mean ELISA Anti-Diphtheria Antibody Concentrations (95%CI) in All Subjects at Day 1 Pre-vaccination in the V98_06 study or V98_06E1 for the Naive Group and at Day 61 Post-vaccination in Study V98_06E1. Anti-diphtheria antibody testing was not performed in this study because no diphtheria vaccine was administered in the study and also because data from other Cross Reactive Material(CRM)-based vaccines demonstrate that administration has not resulted in a decline in anti-diphtheria antibody concentrations.	At Day 1 (V98_06 or V98_06E1) and Day 61