Infections, Streptococcal, Streptococcal Infections
Conditions
Keywords
GBS, vaccine comparability, Group B Strep
Brief summary
The purpose of the present study is to assess and compare in healthy non-pregnant women 18 to 40 years of age the safety and immunogenicity of a liquid formulation of Group B Streptococcus (GBS) Trivalent Vaccine (not requiring reconstitution prior to administration), and of the lyophilized formulation of GBS Trivalent Vaccine, administered in non-pregnant and pregnant women in the clinical development program to date.
Interventions
BIOLOGICALGBS Vaccine
Liquid formulation of a vaccine containing polysaccharide capsules from serotypes Ia, Ib, and III of the Group B Streptococcus
Sponsors
Novartis Vaccines
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy females 18-40 years of age, inclusive. 2. Individuals who have given written consent after the nature of the study has been explained according to local regulatory requirements. 3. Individuals in good health as determined by the outcome of medical history, physical examination and clinical judgment of the investigator. 4. Individuals who can comply with all study procedures and are available for follow-up.
Exclusion criteria
1. Individuals who are pregnant (urine pregnancy test at Study Day 1) or who anticipate becoming pregnant prior to the end of the study, Day 181 Visit. 2. Individuals of childbearing potential, heterosexually active, and has not used any of the acceptable contraceptive methods for at least 2 months prior to study entry and who will not continue to use acceptable contraceptive methods through to the end of the study, Day 181 Visit. * Of childbearing potential is defined as status post onset of menarche and not meeting any of the following conditions: menopausal for at least 2 years, status after bilateral tubal ligation for at least 1 year, status after bilateral oophorectomy, or status after hysterectomy. * Acceptable birth control methods are defined as one or more of the following: hormonal contraceptive (such as oral, injection, transdermal patch, implant, cervical ring); barrier (condom with spermicide or diaphragm with spermicide) each and every time during intercourse; intrauterine device (IUD); monogamous relationship with vasectomized partner who was vasectomized for at least six months prior to the subject's study entry; or abstinence/no sexual intercourse. 3. Individuals who are nursing (breastfeeding). 4. Individuals who have participated in any clinical trial with another investigational product 30 days prior to first study visit or who intend to participate in another trial prior to the end of the study, Day 181 Visit. 5. Individuals who have had a previous immunization with a vaccine containing Group B Streptococcus antigens. 6. Individuals who receive: * live vaccine 30 days prior to study vaccination * inactivated vaccines 15 days prior to study vaccination * any vaccines within 30 days after 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 with a fever (oral temperature ≥ 38°C) within 3 days prior to Study Day 1. 8. Individuals with acute or chronic infection(s) (e.g. requiring systemic antibiotic treatment or antiviral therapy) within 7 days prior to Study Day 1. 9. Individuals with a history of severe allergic reactions after previous vaccination or medication such as anaphylactic shock, asthma, urticaria, or other allergic reaction or hypersensitivity to any vaccine component. 10. Individuals with known or suspected impairment of the immune system including known or suspected HIV infection or HIV-related disease, a history of or an active autoimmune disorder and receipt of immunosuppressive therapy. 11. Long term use of glucocorticoids, including oral or parenteral prednisone ≥ 20 mg/day or equivalent for more than 2 consecutive weeks (or 2 weeks total) within 30 days prior to enrollment. Use of inhaled, intranasal, intra-articular, or topical corticosteroids is allowed. 12. Individuals who have received blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation in the past 12 weeks. 13. Individuals with any progressive or severe neurologic disorder, seizure disorder, epilepsy or Guillain-Barré syndrome. 14. Individuals with 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. 15. Individuals who are not able to comprehend and to follow all required study procedures for the whole period of the study. 16. Individuals with history or any illness that, in the opinion of the investigator, might interfere with results of the study or pose additional risk to subjects due to participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Concentration of Serotype Ia GBS IgG Levels in Healthy Non-pregnant Women | At Day 31 after a single vaccination | To evaluate serotype-specific Ia GBS serum IgG antibody levels (anti-Ia) in healthy non-pregnant women when administered with the liquid GBS trivalent vaccine formulation or the lyophilized GBS trivalent vaccine formulation. Antibody concentrations were measured by Enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL). |
| Concentration of Serotype III GBS IgG Levels in Healthy Non-pregnant Women | At Day 31 after a single vaccination | To evaluate serotype-specific III GBS serum IgG antibody levels (anti-III) in healthy non-pregnant women when administered with the liquid GBS trivalent vaccine formulation or the lyophilized GBS trivalent vaccine formulation. Antibody concentrations were measured by Enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL). |
| Concentration of Serotype Ib GBS IgG Levels in Healthy Non-pregnant Women | At Day 31 after a single vaccination | To evaluate serotype-specific Ib GBS serum IgG antibody levels (anti-Ib) in healthy non-pregnant women when administered with the liquid GBS trivalent vaccine formulation or the lyophilized GBS trivalent vaccine formulation. Geometric mean concentrations (GMCs) were measured and expressed in micrograms per milliliter (μg/mL). As the singleton ELISA was no longer in use at the time of serotype Ib testing, results were obtained using multiplex immunoassay. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Reporting Any Unsolicited AEs | From Day 1 to Day 181 (end of the study) | Safety was assessed as the number of subjects who reported unsolicited AEs following a single injection with either liquid or lyophilized GBS trivalent vaccine formulations. |
| Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs) | From 6 hours through Day 7 post-vaccination | Safety was assessed as the number of subjects who reported solicited local and solicited systemic AEs following a single injection with either liquid or lyophilized GBS trivalent vaccine formulations. |
| Number of Subjects Reporting Any Serious Adverse Events (SAEs) | From Day 1 to Day 181 (end of the study) | Safety was assessed as the number of subjects who reported SAEs following a single injection with either liquid or lyophilized GBS trivalent vaccine formulations. |
Countries
Belgium, Czechia, United States
Participant flow
Recruitment details
1053 subjects were enrolled at Belgium, US and Czech Republic sites.
Pre-assignment details
Among the 1053 subjects enrolled in the study, 3 subjects were randomized but didn't receive the vaccine. The 3 subjects were excluded and didn't start the study.
Participants by arm
| Arm | Count |
|---|---|
| Liquid GBS Trivalent Vaccine Healthy non-pregnant women aged 18-40 years that received a single dose of liquid GBS trivalent vaccine | 529 |
| Lyophilized GBS Trivalent Vaccine Healthy non-pregnant women aged 18-40 years that received a single dose of lyophilized GBS trivalent vaccine | 521 |
| Total | 1,050 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 9 | 4 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Liquid GBS Trivalent Vaccine | Lyophilized GBS Trivalent Vaccine | Total |
|---|---|---|---|
| Age, Continuous | 27.1 Years STANDARD_DEVIATION 6.24 | 27.4 Years STANDARD_DEVIATION 6.05 | 27.2 Years STANDARD_DEVIATION 6.15 |
| Sex: Female, Male Female | 529 Participants | 521 Participants | 1050 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 526 | 0 / 521 |
| other Total, other adverse events | 439 / 526 | 430 / 521 |
| serious Total, serious adverse events | 6 / 526 | 9 / 521 |
Outcome results
Primary
Concentration of Serotype Ia GBS IgG Levels in Healthy Non-pregnant Women
To evaluate serotype-specific Ia GBS serum IgG antibody levels (anti-Ia) in healthy non-pregnant women when administered with the liquid GBS trivalent vaccine formulation or the lyophilized GBS trivalent vaccine formulation. Antibody concentrations were measured by Enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL).
Time frame: At Day 31 after a single vaccination
Population: All subjects in the Full Analysis Set immunogenicity population who received the study vaccine, have no major protocol deviation or other reasons to be excluded as defined prior to unblinding \& provided evaluable serum samples both before vaccination and at Day 31 in the protocol required windows.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Liquid GBS Trivalent Vaccine | Concentration of Serotype Ia GBS IgG Levels in Healthy Non-pregnant Women | 6.81 µg/mL |
| Lyophilized GBS Trivalent Vaccine | Concentration of Serotype Ia GBS IgG Levels in Healthy Non-pregnant Women | 6.66 µg/mL |
Comparison: To demonstrate the equivalence of the liquid GBS trivalent vaccine formulation to the lyophilized GBS trivalent vaccine formulation for serotypes Ia when administered to healthy non-pregnant women, as measured by geometric mean concentrations (GMC).95% CI: [0.79, 1.32]ANCOVA
Primary
Concentration of Serotype Ib GBS IgG Levels in Healthy Non-pregnant Women
To evaluate serotype-specific Ib GBS serum IgG antibody levels (anti-Ib) in healthy non-pregnant women when administered with the liquid GBS trivalent vaccine formulation or the lyophilized GBS trivalent vaccine formulation. Geometric mean concentrations (GMCs) were measured and expressed in micrograms per milliliter (μg/mL). As the singleton ELISA was no longer in use at the time of serotype Ib testing, results were obtained using multiplex immunoassay.
Time frame: At Day 31 after a single vaccination
Population: All subjects in the Full Analysis Set immunogenicity population who received the study vaccine, have no major protocol deviation or other reasons to be excluded as defined prior to unblinding \& provided evaluable serum samples both before vaccination and at Day 31 in the protocol required windows.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Liquid GBS Trivalent Vaccine | Concentration of Serotype Ib GBS IgG Levels in Healthy Non-pregnant Women | 2.94 µg/mL |
| Lyophilized GBS Trivalent Vaccine | Concentration of Serotype Ib GBS IgG Levels in Healthy Non-pregnant Women | 3.14 µg/mL |
Comparison: to demonstrate the equivalence of the liquid GBS trivalent vaccine formulation to the lyophilized GBS trivalent vaccine formulation for serotypes Ib when administered to healthy non-pregnant women, as measured by geometric mean concentrations (GMC).95% CI: [0.72, 1.22]ANCOVA
Primary
Concentration of Serotype III GBS IgG Levels in Healthy Non-pregnant Women
To evaluate serotype-specific III GBS serum IgG antibody levels (anti-III) in healthy non-pregnant women when administered with the liquid GBS trivalent vaccine formulation or the lyophilized GBS trivalent vaccine formulation. Antibody concentrations were measured by Enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL).
Time frame: At Day 31 after a single vaccination
Population: All subjects in the Full Analysis Set immunogenicity population who received the study vaccine, have no major protocol deviation or other reasons to be excluded as defined prior to unblinding \& provided evaluable serum samples both before vaccination and at Day 31 in the protocol required windows.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Liquid GBS Trivalent Vaccine | Concentration of Serotype III GBS IgG Levels in Healthy Non-pregnant Women | 2.42 µg/mL |
| Lyophilized GBS Trivalent Vaccine | Concentration of Serotype III GBS IgG Levels in Healthy Non-pregnant Women | 2.44 µg/mL |
Comparison: to demonstrate the equivalence of the liquid GBS trivalent vaccine formulation to the lyophilized GBS trivalent vaccine formulation for serotypes III when administered to healthy non-pregnant women, as measured by geometric mean concentrations (GMC).95% CI: [0.76, 1.3]ANCOVA
Secondary
Number of Subjects Reporting Any Serious Adverse Events (SAEs)
Safety was assessed as the number of subjects who reported SAEs following a single injection with either liquid or lyophilized GBS trivalent vaccine formulations.
Time frame: From Day 1 to Day 181 (end of the study)
Population: Analyses were evaluated on the Unsolicited AEs Safety Set (i.e. all subjects in the exposed set who provided information about post vaccination unsolicited AEs). There were 3 subjects in the Liquid GBS trivalent vaccine group who were treated but for whom no safety data were available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Liquid GBS Trivalent Vaccine | Number of Subjects Reporting Any Serious Adverse Events (SAEs) | Serious AEs | 6 Subjects |
| Liquid GBS Trivalent Vaccine | Number of Subjects Reporting Any Serious Adverse Events (SAEs) | At least possibly or probably related SAEs | 0 Subjects |
| Lyophilized GBS Trivalent Vaccine | Number of Subjects Reporting Any Serious Adverse Events (SAEs) | Serious AEs | 9 Subjects |
| Lyophilized GBS Trivalent Vaccine | Number of Subjects Reporting Any Serious Adverse Events (SAEs) | At least possibly or probably related SAEs | 0 Subjects |
Secondary
Number of Subjects Reporting Any Unsolicited AEs
Safety was assessed as the number of subjects who reported unsolicited AEs following a single injection with either liquid or lyophilized GBS trivalent vaccine formulations.
Time frame: From Day 1 to Day 181 (end of the study)
Population: Analyses were evaluated on the Unsolicited AEs Safety Set (i.e. all subjects in the exposed set who provided information about post vaccination unsolicited AEs). There were 3 subjects in the Liquid GBS trivalent vaccine group who were treated but for whom no safety data were available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Liquid GBS Trivalent Vaccine | Number of Subjects Reporting Any Unsolicited AEs | Any AEs | 272 Subjects |
| Liquid GBS Trivalent Vaccine | Number of Subjects Reporting Any Unsolicited AEs | At least possibly or probably related AEs | 57 Subjects |
| Liquid GBS Trivalent Vaccine | Number of Subjects Reporting Any Unsolicited AEs | Medically attended AEs | 165 Subjects |
| Liquid GBS Trivalent Vaccine | Number of Subjects Reporting Any Unsolicited AEs | AEs leading to Withdrawal | 0 Subjects |
| Liquid GBS Trivalent Vaccine | Number of Subjects Reporting Any Unsolicited AEs | AEs leading to Hospitalization | 5 Subjects |
| Liquid GBS Trivalent Vaccine | Number of Subjects Reporting Any Unsolicited AEs | AEs leading to Death | 0 Subjects |
| Lyophilized GBS Trivalent Vaccine | Number of Subjects Reporting Any Unsolicited AEs | AEs leading to Hospitalization | 9 Subjects |
| Lyophilized GBS Trivalent Vaccine | Number of Subjects Reporting Any Unsolicited AEs | Any AEs | 276 Subjects |
| Lyophilized GBS Trivalent Vaccine | Number of Subjects Reporting Any Unsolicited AEs | AEs leading to Withdrawal | 0 Subjects |
| Lyophilized GBS Trivalent Vaccine | Number of Subjects Reporting Any Unsolicited AEs | At least possibly or probably related AEs | 52 Subjects |
| Lyophilized GBS Trivalent Vaccine | Number of Subjects Reporting Any Unsolicited AEs | AEs leading to Death | 0 Subjects |
| Lyophilized GBS Trivalent Vaccine | Number of Subjects Reporting Any Unsolicited AEs | Medically attended AEs | 166 Subjects |
Secondary
Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs)
Safety was assessed as the number of subjects who reported solicited local and solicited systemic AEs following a single injection with either liquid or lyophilized GBS trivalent vaccine formulations.
Time frame: From 6 hours through Day 7 post-vaccination
Population: Analyses were evaluated on the Solicited Safety Set (i.e. all subjects in the exposed set with data on post vaccination local or systemic AEs or other signs of reactogenicity). For 3 treated subjects in the Liquid GBS trivalent vaccine group, no safety data were available and for 4 subjects from both groups, no solicited safety data were reported.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Liquid GBS Trivalent Vaccine | Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs) | Injection site Swelling | 12 Participants |
| Liquid GBS Trivalent Vaccine | Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs) | Nausea | 83 Participants |
| Liquid GBS Trivalent Vaccine | Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs) | Injection site Ecchymosis | 1 Participants |
| Liquid GBS Trivalent Vaccine | Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs) | Headache | 176 Participants |
| Liquid GBS Trivalent Vaccine | Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs) | Injection site Warmth | 68 Participants |
| Liquid GBS Trivalent Vaccine | Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs) | Fatigue | 183 Participants |
| Liquid GBS Trivalent Vaccine | Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs) | Injection site Induration | 17 Participants |
| Liquid GBS Trivalent Vaccine | Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs) | Rash | 18 Participants |
| Liquid GBS Trivalent Vaccine | Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs) | Chills | 64 Participants |
| Liquid GBS Trivalent Vaccine | Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs) | Arthralgia | 49 Participants |
| Liquid GBS Trivalent Vaccine | Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs) | Injection site Pain | 227 Participants |
| Liquid GBS Trivalent Vaccine | Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs) | Fever (≥38°C) | 8 Participants |
| Liquid GBS Trivalent Vaccine | Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs) | Myalgia | 75 Participants |
| Liquid GBS Trivalent Vaccine | Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs) | Analgesic/antipyrectic use (prevention) | 2 Participants |
| Liquid GBS Trivalent Vaccine | Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs) | Injection site Erythema | 16 Participants |
| Liquid GBS Trivalent Vaccine | Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs) | Analgesic/antipyrectic use (treatment) | 59 Participants |
| Liquid GBS Trivalent Vaccine | Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs) | Malaise | 104 Participants |
| Liquid GBS Trivalent Vaccine | Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs) | Any Systemic AEs | 280 Participants |
| Liquid GBS Trivalent Vaccine | Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs) | Any local AEs | 247 Participants |
| Lyophilized GBS Trivalent Vaccine | Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs) | Any Systemic AEs | 278 Participants |
| Lyophilized GBS Trivalent Vaccine | Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs) | Any local AEs | 229 Participants |
| Lyophilized GBS Trivalent Vaccine | Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs) | Injection site Erythema | 9 Participants |
| Lyophilized GBS Trivalent Vaccine | Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs) | Injection site Induration | 15 Participants |
| Lyophilized GBS Trivalent Vaccine | Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs) | Injection site Ecchymosis | 6 Participants |
| Lyophilized GBS Trivalent Vaccine | Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs) | Injection site Pain | 205 Participants |
| Lyophilized GBS Trivalent Vaccine | Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs) | Injection site Swelling | 5 Participants |
| Lyophilized GBS Trivalent Vaccine | Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs) | Injection site Warmth | 57 Participants |
| Lyophilized GBS Trivalent Vaccine | Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs) | Chills | 56 Participants |
| Lyophilized GBS Trivalent Vaccine | Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs) | Myalgia | 78 Participants |
| Lyophilized GBS Trivalent Vaccine | Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs) | Malaise | 103 Participants |
| Lyophilized GBS Trivalent Vaccine | Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs) | Nausea | 77 Participants |
| Lyophilized GBS Trivalent Vaccine | Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs) | Headache | 187 Participants |
| Lyophilized GBS Trivalent Vaccine | Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs) | Fatigue | 190 Participants |
| Lyophilized GBS Trivalent Vaccine | Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs) | Rash | 15 Participants |
| Lyophilized GBS Trivalent Vaccine | Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs) | Arthralgia | 53 Participants |
| Lyophilized GBS Trivalent Vaccine | Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs) | Fever (≥38°C) | 7 Participants |
| Lyophilized GBS Trivalent Vaccine | Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs) | Analgesic/antipyrectic use (prevention) | 3 Participants |
| Lyophilized GBS Trivalent Vaccine | Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AEs) | Analgesic/antipyrectic use (treatment) | 69 Participants |