Group B Streptococcal Infection
Conditions
Brief summary
A placebo controlled clinical trial investigating the safety and immunogenicity of GBS6 in pregnant women with and without human immunodeficiency virus (HIV) infection and their infants
Detailed description
This Phase 2, randomised, placebo controlled, double blinded study will be the first evaluation of the investigational GBS6 in HIV-infected pregnant women. This study will enroll pregnant women with and without HIV to receive GBS6 or Placebo in order to provide an expanded safety and immunogenicity data set (for both pregnant women and their infants) and to support progression of the development of this vaccine.
Interventions
DRUGGBS6
The investigational products are GBS6 and placebo (saline control). The GBS6 dose will be GBS6 20mcg without AlPO4 (equivalent to 240 mcg/mL) 0.5mL dose or 20 mcg CPS/serotype).
DRUGPlacebo
Placebo (saline control) administered intramuscularly by injecting 0.5 mL into the deltoid muscle
Sponsors
MU-JHU CARE
Pfizer
St George's, University of London
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
Inclusion criteria for Maternal Participants 1. Age ≥ 18 to ≤ 40 years of age, inclusive at day of signing the ICF. 2. Pregnant at ≥ 27 0/7 to ≤35 6/7 gestation on the day of planned vaccination, verified by ultrasound scan (U/S). 3. Low risk, singleton pregnancy, as assessed by the study physician based on ultra-sound scan and previous obstetric history. 4. Documented negative HBV surface antigen, HCV antibody, and syphilis tests at screening. 5. Documented HIV test during pregnancy undertaken as per the national guidelines. 6. If HIV infected pregnant women, stable on ART for at least 3 months prior to study start 7. Determined by medical history, physical examination, screening laboratory assessment, and clinical judgment to be appropriate for inclusion in the study. 8. Receiving prenatal standard of care including HIV care if applicable at the clin-ics/physician offices/hospital network affiliated with the clinical study site. 9. Willing to give birth at Kawempe Specialised National Referral Hospital, or Kisenyi Health center IV, Uganda. 10. Willing and able to participate for the duration of the study visits and follow-up until 12-months post-delivery. 11. Willing and able to be contacted by telephone for the full duration of the study, and to give informed consent for their infant participant to participate in the study. Inclusion criteria for Infants Inclusion criteria for Infants 1\. Parent(s) willing and able to comply with scheduled visits, investigational plan, laboratory tests, and other study procedures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Infant outcome 2 | Through 12 months of age | 2\. Number Occurrence of SAEs, AEs of special interest (major congenital anomalies, developmental delay, and suspected or confirmed GBS infection), and MAEs through 12 months of age and any unsolicited events leading to study withdrawal. |
| Primary Infant outcome 1 | Birth to 6 weeks of age | 1\. Number Occurrence of unsolicited adverse events from birth to 6 weeks of age |
| Primary mother outcome 4 | Visit 1 through 12 months post-delivery | 4\. Number Occurrence of SAEs, MAEs, and obstetric complications (peripartum, intrapartum, and postpartum) throughout the study (Visit 1 through the 12 month postdelivery study visit) and any unsolicited events leading to study withdrawal. |
| Primary mother outcome 1 | 7 days following administration of IMP | 1\. Percentage Occurrence of solicited local reactions within 7 days following administration of investigational product (pain at the injection site, redness, and swelling). |
| Primary mother outcome 3 | Through 1 month following administration of IMP | 3\. Percentage Occurrence of solicited and unsolicited adverse events through 1 month after administration of investigational product. |
| Primary mother outcome 2 | 7 days following administration of IMP | 2\. Percentage Occurrence of solicited systemic events within 7 days following administration of investigational product (fever, nausea/vomiting, diarrhoea, headache, fatigue/tiredness, muscle pain, and joint pain). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary infant Objective 1 - Geometric mean concentration GBS serotype specific IgG antibody titres in HIV-exposed and unexposed infant participants | Birth | 1\. Geometric mean concentration GBS serotype specific IgG antibody titres in HIV-exposed and unexposed infant participants measured at birth |
| Secondary mother Outcome 1 - Geometric mean concentration GBS serotype specific IgG antibody titres in HIV positive and HIV negative women | Baseline | 1\. Geometric mean concentration GBS serotype specific IgG antibody titres measured at baseline in HIV positive and HIV negative women. |
| Secondary Mother Objective 2 - Geometric mean concentration GBS serotype specific IgG titres in HIV positive and HIV negative women | Baseline | 2\. Geometric mean concentration GBS serotype specific IgG titres measured at baseline in HIV positive and HIV negative women. |
| Secondary Mother Objective 2 - Geometric mean concentration GBS serotype specific IgG titres in HIV positive and HIV negative wome | Delivery | 2\. Geometric mean concentration GBS serotype specific IgG titres measured at delivery in HIV positive and HIV negative women. |
| Secondary infant Objective 2 - Geometric mean concentration GBS serotype specific IgG titres in HIV-exposed and unexposed infant participants | 18 weeks of life | 2\. Geometric mean concentration GBS serotype specific IgG titres in HIV-exposed and unexposed infant participants measured at 18 weeks of life. |
| Secondary infant Objective 3 - Ratio Placental transfer ratio of GBS-specific antibodies in HIV-exposed and unexposed pregnancies. | Delivery | 3\. Ratio Placental transfer ratio of GBS-specific antibodies in HIV-exposed and unexposed pregnancies. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Mother Exploratory outcome 1 - Ratio Placental transfer ratio of GBS-specific antibodies in HIV-exposed and unexposed pregnancies. | Baseline through 12 months after delivery | 1\. Fold increase in GBS serotype specific IgG antibody titres over baseline measured before vaccination through 12 months after delivery in HIV positive and HIV negative women. |
| Infant Exploratory outcome 3 - Concentration GBS serotype specific IgG antibody titres measured from dried blood spots in infant participants. | At birth | 3\. Concentration GBS serotype specific IgG antibody titres measured from dried blood spots in infant participants at birth. |
| Infant Exploratory outcome 2 - Concentration Serotype specific GBS positive nasal/rectal cultures in infant participants | Delivery | 2\. Concentration Serotype specific GBS positive nasal/rectal cultures at delivery in infant participants. |
| Infant Exploratory outcome 1 - Concentration IgG antibody titres to vaccines included in the extended programme of vaccination administered to HIV-exposed and unexposed infant participants | 18 weeks of age | Concentration IgG antibody titres to vaccines included in the extended programme of vaccination administered to HIV-exposed and unexposed infant participants as part of at 18 weeks of age |
| Mother Exploratory outcome 3 - Concentration GBS serotype specific IgG and IgA antibody titres in breast milk following vaccination of women living with HIV and their unexposed counterparts | within 72 hours after delivery | 3\. Concentration GBS serotype specific IgG and IgA antibody titres in breast milk following vaccination of women living with HIV and their unexposed counterparts in colostrum (within 72 hours of delivery) |
| Mother Exploratory outcome 2 - Percentage Serotype specific GBS positive vaginal and/or rectal culture(s) in HIV positive and HIV negative women. | Baseline | 2\. Percentage Serotype specific GBS positive vaginal and/or rectal culture(s) before vaccination, at delivery, and 6 weeks after delivery in HIV positive and HIV negative women. |
Countries
Uganda
Outcome results
None listed