Group B Streptococcal Infection
Conditions
Brief summary
A randomised, placebo-controlled, double-blind study to evaluate the safety, tolerability and immunogenicity of the GBS-NN/NN2 (Recombinant protein vaccine against Group B Streptococcus) vaccine in women living with HIV and women without HIV, and their newborn babies from vaccination up to delivery/birth. Mothers and babies will be followed up for 12 months post-delivery.
Detailed description
100 women who are pregnant and living with HIV will randomly receive two 0.5 mL (millilitre) intramuscular injections of GBS-NN/NN2 vaccine (80 women) or placebo (20 women). 100 women who are pregnant and do not have HIV will randomly receive two 0.5 mL intramuscular injections of GBS-NN/NN2 vaccine (80 women) or placebo (20 women). Participants will be screened at 24 to 28 weeks gestation (Days -14 to Day -1) and the groups will be dosed in parallel. The first dose of vaccine or placebo will be administered at Day 0 and the second dose will be administered 28±2 days later. Delivery is anticipated to be approximately 10 to 14 weeks after the first dose of vaccine. For the analysis of the immune response, the placebo groups will be combined. For safety, the placebo groups will be analysed separately and will be combined for comparison with the potential vaccine groups.
Interventions
BIOLOGICALGBS-NN/NN2
GBS-NN/NN2 bound to Alhydrogel as an adjuvant.
BIOLOGICALPlacebo
Normal Saline 0.9%
Sponsors
Minervax ApS
European and Developing Countries Clinical Trials Partnership (EDCTP)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Randomised, placebo controlled, double-blind, parallel group, multicentre study.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
1. Participants at least 18 years old and not older than 40 years of age. 2. Pregnant women who are between 26 weeks and 30 weeks (inclusive) gestation on the planned day of vaccination with a singleton, uncomplicated pregnancy. Gestational age to be determined on the following hierarchal basis with guidance to the GAIA (Global Alignment of Immunisation Safety Assessment in pregnancy) criteria: 1. ultrasound estimate of gestational age, 2. date of last menstrual period 3. fundal height 3. HIV status to be based on rapid, confirmatory test, unless a documented test of the participant being sero-positive for HIV and history documented in the notes. 4. Women living with HIV, HIV viral load \<1000, on antiretroviral therapy for at least 3 months prior to screening and clinically well. 5. Expected to be available for the scheduled clinic visits for the duration of the study, agree to be contacted by telephone during study participation, and is willing to give parental consent for her infant to participate in the study
Exclusion criteria
1. Women who are hepatitis B surface (HBSAg) and/or hepatitis C (HCV) positive 2. Women who test positive for syphilis as per standard testing 3. Women knowingly carrying, at screening, a malformed or genetically abnormal foetus based on ultrasound 4. Women who have experienced a previous stillbirth prior to going into labour 5. Women with placenta previa 6. Women with documented chronic or pregnancy induced hypertension at screening 7. Women with 1+ protein in urine and hypertension defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg) at ≥20 weeks of gestation in a woman with a previously normal blood pressure 8. Women with \>1+ of protein in urine (regardless of blood pressure) 9. Women with gestational, type 1 or type 2 diabetes. 10. Women with glycosuria on dipstick 11. Women known to be allergic to any components of the vaccine, known to be allergic to aluminium or having had an allergic reaction to any previous vaccination. 12. Women with history or presence of significant cardiovascular disease, pulmonary, hepatic, gallbladder or biliary tract, renal, haematological, gastrointestinal, endocrine, immunologic, dermatological, neurological, psychiatric, autoimmune disease, cognitive disorder or current infection and significant illness 4 weeks prior to randomization. 13. Women with current or history of drug or alcohol abuse within the last two years. 14. Women who have received a vaccine within 28 days of receiving the first dose of GBS NN/NN2 or placebo or who expect to require vaccination during the course of the study. (Vaccines recommended for administration during pregnancy e.g. tetanus toxoid, pertussis and influenza are permitted. Administration of concurrent vaccines must not be within 7 days of investigational vaccine.) 15. Women who have a fever (axillary temperature \>37.9°C) on the day of dosing or have had an acute infection in the 7 days before dosing. 16. Women who have any bleeding disorders that prolong the bleeding time. 17. Women who are receiving immunosuppressive medication, including systemic steroids (inhaled and topical steroids are acceptable). 18. Women who have received blood or blood products and/or plasma derivatives or any immunoglobulin preparations in 12 weeks preceding screening. 19. Women with severe anaemia, haemoglobin \< 9g/dL (90 g/L) as per Sheffield grading system ( \> Grade 1) 20. Women who are currently breast feeding 21. Women who are part of the study personnel or a close family member of study personnel. 22. Women who in the opinion of the investigator are not suitable to participate in the study. 23. Concurrent participation in another clinical trial during which subject will be exposed to an investigational product.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment Emergent Adverse Events (TEAEs) in Maternal Participants | From first vaccination (26 to 30 weeks of gestation) up to 28 days post-delivery, up to 24 weeks | Incidence of all TEAEs in maternal participants from first vaccination up to 28 days post-delivery. |
| Incidence of Adverse Events (AEs) in Newborn Babies | From birth to first visit after birth (28±4 days post-delivery) | Incidence of AEs in Newborn babies From birth to first visit after birth (visit 6). |
| Number of Maternal Participants With Solicited Local AEs Within 7 Days After Each Study Vaccine Dose | For 7 days after each study vaccine dose (first vaccine administered at baseline, second vaccine administered 28 days post baseline) | Number of maternal participants with solicited local AEs within 7 Days after each study vaccine dose, defined as: injection site redness, bruising, swelling, itching, pain and tenderness. Injection-site redness was graded based on measurements in centimeter (cm) as grade 0 (no visible redness), grade 1 (mild; 0-2 cm), grade 2 (moderate; 2.1-5 cm) or grade 3 (severe; \> 5 cm). Swelling was graded as grade 0 (no swelling detected), grade 1 (palpable "firmness" only), grade 2 (0-4 cm) or grade 3 (\> 4 cm). Pain at the injection site was rated on a visual analogue scale of 0 to 10, where 0 is no pain and 10 is extreme pain/worst possible pain. Bruising, itching and tenderness were categorised as either yes (present) or no (absent). |
| Number of Maternal Participants With Solicited Systemic AEs Within 7 Days After Each Study Vaccine Dose | For 7 days after each study vaccine dose (first vaccine administered at baseline, second vaccine administered 28 days post baseline) | Number of maternal participants with solicited systemic AEs within 7 days after each study vaccine dose, defined as: headache, sore throat, "flu-like" symptoms, muscle aches, fever in the 72 hours post dose. |
| Gestational Age of Newborn Baby | At birth | Gestational age of newborn baby |
| Weight of Newborn Baby | At birth | Weight of newborn baby |
| Length of Newborn Baby | At birth | Length of newborn baby |
| Head Circumference of Newborn Baby | At birth | Head circumference of newborn baby |
| Apgar Score for Newborn Baby | At birth | APGAR (Appearance, Pulse, Grimace, Activity, Respiration) score of newborn baby were measured at 1, 5 and 10 minutes. The APGAR score is a rapid clinical assessment tool used immediately after birth to evaluate a newborn's physical condition. It evaluates five criteria : Appearance (skin color), Pulse (heart rate), Grimace (Reflex irritability), Activity (muscle tone), Respiration (breathing effort), each category is scored 0, 1, or 2, where 2 indicates optimal function. Total score ranges from 0 to 10: 7-10: Normal / Reassuring - baby adapting well 4-6: Moderately abnormal - may need assisted breathing or additional monitoring 0-3: Low - requires immediate resuscitation and urgent intervention |
| Transfer Rate (Baby/Mother) of IgG Antibody Concentrations | At delivery | For each of the specific IgG antibody concentrations, the transfer rate is defined as concentration in baby at birth/concentration in mother at delivery, expressed as a percentage. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Significant Adverse Reactions in Mothers | From delivery to 6 months post-delivery | Incidence of significant adverse reactions in maternal participants |
| Developmental Milestones of Babies | At 6 months | Developmental milestones at 6 months were assessed using the Ages and Stages Questionnaire, Third Edition (ASQ-3), a validated developmental screening tool designed to evaluate early childhood development across 5 key domains: communication, gross motor, fine motor, problem solving, and personal-social. Each domain includes 6 items scored as Yes (10), Sometimes (5), or Not yet (0). Domain scores are calculated by summing item scores (range: 0-60 per domain); higher scores indicate better development. A total score (sum of all domains) may be calculated (range: 0-300), though interpretation relies primarily on domain scores. For each domain, the cut-offs are 29.65 for Communication, 22.25 for Gross Motor, 25.14 for Fine Motor, 27.72 for Problem Solving, and 25.34 for Personal-Social. Scores above these thresholds generally indicate development on schedule, while scores near the cutoff suggest monitoring, and scores below warrant additional assessment or referral. |
| Geometric Mean Antibody Concentration in Maternal Participants (4 Weeks) | At 4 weeks post first injection and at 4 weeks post second injection | Geometric mean IgG antibody concentration in the maternal participants specific to Alpha Like Protein 1 (Alp1), Alpha Like Protein 2 (Alp2), Alpha Like Protein C (AlpC) and Rib protein (Rib). |
| Geometric Mean Antibody Concentration in Maternal Blood at 6 Months Post-delivery | 6 months post-delivery | Geometric mean antibody concentration specific to Alp1, Alp2, AlpC and Rib in maternal blood at 6 months post-delivery |
| Geometric Mean Antibody Concentration in Infant Blood at 1, 2, and 3 Months Post-delivery | At 1, 2, and 3 months post-delivery | Geometric mean antibody concentration specific to Alp1, Alp2, AlpC and Rib in infant blood at 1, 2, and 3 months post-delivery |
| Geometric Mean Antibody Concentration in Newborns | Within 48 hours of birth. | Geometric mean antibody concentration specific to Alp1, Alp2, AlpC and Rib in newborn blood within 48 hours of birth. |
| Geometric Mean Antibody Concentration From Maternal Blood at Delivery | At delivery | Geometric mean antibody concentration specific to Alp1, Alp2, AlpC and Rib from maternal blood at delivery |
| Geometric Mean Fold Increase in Antibody Concentration in Maternal Blood | At 4 weeks post first injection and at 4 weeks post second injection | Geometric mean fold increase in IgG specific antibody concentration (Alp1, Alp2, AlpC and Rib) in maternal blood from baseline to 4 weeks after vaccination with the first and second dose. |
| Proportion of Mothers Achieving Vaccine Specific IgG Antibody Concentrations | At delivery | Proportion of mothers achieving vaccine specific IgG antibody concentrations in maternal samples respectively, above pre-defined arbitrary thresholds (0.5, 1, 2 μg/mL). |
| Proportion of Newborn Babies Achieving Vaccine Specific IgG Antibody Concentrations | At birth | Proportion of newborn babies achieving vaccine specific IgG antibody concentrations above pre-defined arbitrary thresholds (0.5, 1, 2 μg/mL). |
Countries
South Africa, Uganda
Contacts
STUDY_DIRECTORCornelia Oostvogels
Minervax ApS
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 200 Participants |
| Age, Continuous | 28.9 years STANDARD_DEVIATION 5.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 80 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 78 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment South Africa | 150 participants |
| Region of Enrollment Uganda | 21 participants |
| Sex: Female, Male Female | 200 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 80 | 0 / 80 | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 62 / 80 | 61 / 80 | 14 / 20 | 15 / 20 |
| serious Total, serious adverse events | 29 / 80 | 23 / 80 | 7 / 20 | 6 / 20 |
Outcome results
None listed