Clinical Trial Investigating the Safety and Immunogenicity of GBS6 in Pregnant Women (PREPARE)

Study Overview
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Brief Summary
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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
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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 the GBS6 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.

Official Title
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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

Conditions
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Group B Streptococcal Infection

Intervention / Treatment
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* Drug: GBS6


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion criteria for Maternal Participants Age ≥ 18 to ≤ 40 years of age, inclusive at day of signing the ICF. Pregnant at ≥ 27 0/7 to ≤35 6/7 gestation on the day of planned vaccination, verified by ultrasound scan (U/S). Low risk, singleton pregnancy, as assessed by the study physician based on ultra-sound scan and previous obstetric history. Documented negative HBV surface antigen, HCV antibody, and syphilis tests at screening. Documented HIV test during pregnancy undertaken as per the national guidelines. If HIV infected pregnant women, stable on ART for at least 3 months prior to study start Determined by medical history, physical examination, screening laboratory assessment, and clinical judgment to be appropriate for inclusion in the study. Receiving prenatal standard of care including HIV care if applicable at the clin-ics/physician offices/hospital network affiliated with the clinical study site. Willing to give birth at Kawempe Specialised National Referral Hospital, or Kisenyi Health center IV, Uganda. Willing and able to participate for the duration of the study visits and follow-up until 12-months post-delivery. 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. Exclusion Criteria: Exclusion criteria for Maternal Participants Any of the following: Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or participants who are Pfizer employees, including their family members, directly involved in the conduct of the study. Participants whose unborn baby have been fathered by investigational site staff members directly involved in the conduct of the study or their family members, site staff members otherwise supervised by the investigator, or Pfizer employees directly involved in the conduct of the study. Participation in other studies involving investigational drug(s), vaccines, or medical devices within 28 days prior to study entry and/or during study participation. Previous vaccination with any licensed or investigational GBS vaccine. History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (e.g., anaphylaxis) to any component of the investigational product. History of microbiologically proven invasive disease caused by GBS, or history of an infant with GBS disease. Current alcohol abuse or illicit drug use. Body mass index (BMI) of ≥40 kg/m2 at the time of the screening visit. Clinical history of primary genital herpes simplex virus (HSV) infection during the current pregnancy. A prior history of or current pregnancy complications or abnormalities that will increase the risk associated with the participant's participation in, and completion of, the study, including but not limited to the following (refer to the SRM) for further details): Gestational hypertension or preeclampsia eclampsia Placental abnormality Polyhydramnios or oligohydramnios Significant bleeding or blood clotting disorder Gestational diabetes Any signs of premature labour with the current pregnancy Prior late stillbirth (defined as loss of pregnancy at any time after 28 weeks gestation) or neonatal death (defined as death of an infant within the first 28 days of life), prior low birth weight baby (defined as infant <2500 g) or premature delivery (defined as delivery before 37 0/7 weeks gestation), prior history of at least 3 miscarriages, prior pregnancies numbering greater than 5, or previous infant with a known or suspected genetic disorder or major congenital anomaly Confirmed GBS bacteriuria during the current pregnancy Major illness of the mother (outside of HIV serostatus) or conditions of the foetus that, in the investigator's judgment, will substantially increase the risk associated with the participant's participation in, and completion of, the study or could preclude the evaluation of the participant's response, including but not limited to the following (refer to the SRM) for further details): g. hypertension requiring treatment h. heart disease i. lung disease j. neurological disorders including a history of epilepsy or recurrent afebrile seizures k. kidney disease l. liver disease m. haematological disorders (including sickle cell disease) n. severe anaemia (less than 7.0g/dL) o. significant bleeding or blood clotting disorder p. endocrine disorders including known diabetes mellitus Participants with known or suspected immunodeficiency (outside of HIV positive sero-status). Participants who receive treatment with immunosuppressive therapy including cytotoxic agents or systemic corticosteroids, e.g., for cancer or an autoimmune disease, or planned receipt through the postvaccination blood draw. Inhaled/nebulised, intra articular, intra-bursal, or topical (skin or eyes) corticosteroids are permitted. Receipt of blood/plasma products or immunoglobulin, from 60 days before investigational product administration, or planned receipt through delivery. Known to be Rhesus Negative Psychiatric condition including recent (within the last year) or active suicidal ideation or behaviour or laboratory abnormalities that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study. Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalised involuntarily.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo (saline) in HIV-uninfected pregnant woman<br>Placebo (saline control) administered intramuscularly by injecting 0.5 mL into the deltoid muscle | Drug: GBS6<br>* 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).<br>* Other names: Hexavalent anti capsular polysaccharide (CPS) / cross reactive material 197 glycoconjugate;|
| Active Comparator: GBS6 in HIV-uninfected pregnant woman<br>GBS6 administered intramuscularly by injecting 0.5 mL into the deltoid muscle | Drug: GBS6<br>* 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).<br>* Other names: Hexavalent anti capsular polysaccharide (CPS) / cross reactive material 197 glycoconjugate;|
| Placebo Comparator: Placebo (saline) in HIV-infected pregnant woman<br>Placebo (saline control) administered intramuscularly by injecting 0.5 mL into the deltoid muscle | Drug: GBS6<br>* 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).<br>* Other names: Hexavalent anti capsular polysaccharide (CPS) / cross reactive material 197 glycoconjugate;|
| Active Comparator: GBS6 in HIV-infected pregnant woman<br>GBS6 administered intramuscularly by injecting 0.5 mL into the deltoid muscle | Drug: GBS6<br>* 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).<br>* Other names: Hexavalent anti capsular polysaccharide (CPS) / cross reactive material 197 glycoconjugate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary mother outcome 1 | 1. Percentage Occurrence of solicited local reactions within 7 days following administration of investigational product (pain at the injection site, redness, and swelling). | 2 years | 
| Primary mother outcome 2 | 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). | 2 years | 
| Primary mother outcome 3 | 3. Percentage Occurrence of solicited and unsolicited adverse events through 1 month after administration of investigational product. | 2 years | 
| Primary mother outcome 4 | 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. | 2 years | 
| Primary Infant outcome 1 | 1. Number Occurrence of unsolicited adverse events from birth to 6 weeks of age | 2 years | 
| Primary Infant outcome 2 | 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. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary mother Outcome 1 | 1. Geometric mean concentration GBS serotype specific IgG antibody titres measured at baseline, 2 weeks, 1 month after vaccination, at delivery and 6 weeks after delivery in HIV positive and HIV negative women. | 2 years | 
| Secondary Mother Objective 2 | 2. Geometric mean concentration GBS serotype specific OPA titres measured at baseline, and at delivery in HIV positive and HIV negative women. | 2 years | 
| Secondary infant Objective 1 | 1. Geometric mean concentration GBS serotype specific IgG antibody titres in HIV-exposed and unexposed infant participants measured at birth, 18 weeks and 12 months of life. | 2 years | 
| Secondary infant Objective 2 | 2. Geometric mean concentration GBS serotype specific OPA titres in HIV-exposed and unexposed infant participants measured at 18 weeks of life. | 2 years | 
| Secondary infant Objective 3 | 3. Ratio Placental transfer ratio of GBS-specific antibodies in HIV-exposed and unexposed pregnancies. | 2 years |