Group B Strep Infection
Conditions
Brief summary
A Phase I, randomised, single centre, double-blind, placebo-controlled, parallel group study to evaluate the safety, tolerability and immunogenicity of two doses of Group B Streptococcus vaccine.
Detailed description
There will be 4 arms in 2 cohorts of 30 subjects. Cohort 1 will receive two 0.5 mL injections, 4 weeks apart, each consisting of 25 μg of GBS-NN and 25 μg of GBS-NN2 (24 subjects) or placebo (6 subjects). Cohort 2 (30 subjects) will receive two 0.5 mL injections, 4 weeks apart, each consisting of 50 μg of GBS-NN and 50 μg of GBS-NN2 (24 subjects) or placebo (6 Subjects). All vaccines will be adsorbed to 500 μg Al3+ as Alhydrogel®. Safety will be assessed after all subjects have completed Visit 4 (Day 8) for Cohort 1, at which point the decision will be made as to whether proceeding with administration of the doses in cohort 2 is appropriate.
Interventions
BIOLOGICALGBS-NN/NN2 with Alhydrogel® 50
GBS-NN/NN2 with Alhydrogel® vaccine will administered to subjects intramuscular 2 times with 4 weeks apart
BIOLOGICALGBS-NN/NN2 with Alhydrogel® 25
GBS-NN/NN2 with Alhydrogel® vaccine will administered to subjects intramuscular 2 times with 4 weeks apart
BIOLOGICALPlacebo GBS-NN/NN2 with Alhydrogel® 25
GBS-NN/NN2 with Alhydrogel® vaccine will administered to subjects intramuscular 2 times with 4 weeks apart
BIOLOGICALPlacebo GBS-NN/NN2 with Alhydrogel® 50
GBS-NN/NN2 with Alhydrogel® vaccine will administered to subjects intramuscular 2 times with 4 weeks apart
Sponsors
Simbec Research
Minervax ApS
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy female subjects aged 18 - 40 years. 2. Body mass index (BMI) ≥18 and ≤30 kg/m2. 3. Subjects weight ≥50kg and ≤100kg at screening. 4. Able to voluntarily provide written informed consent to participate in the study. 5. Subjects are pre-menopausal. 6. Females of childbearing potential must have a negative pregnancy test at screening (β HCG) and prior to each dose. To prevent pregnancy female subjects of childbearing potential must take adequate contraceptive precautions for the entire duration of study participation (up to Day 85). Adequate and highly effective contraceptive precautions include: * Established use of oral, injected or implanted hormonal methods of contraception. * Placement of an intrauterine device (IUD) or intrauterine system (IUS). * Barrier methods of contraception: Condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository. * Male sterilisation (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate). \[For female subjects, the vasectomised male partner should be the sole partner for that subject\]. * True abstinence, when this is in line with the preferred and usual lifestyle of the subject. \[Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\]. • The chosen contraception method(s) must be followed from the first dose until at least Day 85 of the study. 7. Non-smokers for at least 3 months prior to first study vaccine administration.
Exclusion criteria
1. Subjects who have received GBS-NN vaccine previously. 2. Subjects with history or presence of significant cardiovascular disease, pulmonary, hepatic, gallbladder or biliary tract, renal, haematological, gastrointestinal, endocrine, immunologic, dermatological, neurological, psychiatric, autoimmune disease or current infection. 3. Pregnant or lactating females. 4. Laboratory values at screening which are deemed by the investigator to be clinically significantly abnormal. 5. Positive drug screen for drugs of abuse or a positive alcohol urine test prior to first dosing unless there is a documented medical explanation for the positive result other than drugs of abuse (e.g., the subject has been prescribed opioids for pain). 6. Positive for human immunodeficiency virus (HIV), hepatitis B or hepatitis C. 7. Participation in a clinical drug study during the 90 days preceding the initial dose in this study. 8. Any significant illness during the 4 weeks preceding check-in for this study (Day 1). 9. Subjects with a history of allergic reactions after previous vaccination. 10. Subjects who have received any vaccine within 30 days of screening, or who are planning to receive a vaccine up to Day 85 of the study. 11. Subjects receiving immunosuppressive therapy in the 6 months prior to screening, taking any short-term medications including over-the-counter (OTC) preparations, within 7 days of the first dose. Chronic medications such as antihypertensives, bronchodilators, oral contraceptives or statins that do not affect the immune system, will be permitted and allowed to continue during the study at the discretion of the Investigator. Paracetamol will be permitted for the treatment of headache or other symptoms. Use of OTC vitamins and dietary supplements is allowed 12. Subjects with tattoos at the proposed site of vaccine administration. 13. Donation of blood or blood products within 90 days prior to vaccine administration or intending to donate blood or blood products within 90 days of the last visit. 14. Subjects who, in the opinion of the Investigator, are unsuitable for participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events | 85 days | Number of Participants with Treatment Emergent Adverse Events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immunoglobulin(Ig)G Antibody Concentration | Day 85 | Adjusted geometric mean concentration (GMC) |
| Fold Change in Antibody Concentration | Day 1 to Day 85 | Geometric mean fold change in antibody concentration from Day 1 to Day 85 for each group. |
| Seroconversion Rate | Day 85 | 4-fold increase in Immunoglobulin(Ig)G antibody concentration |
| Number of Participants With an Immune Response to First and Second Doses | Day 29 and Day 85 | Number of participants with Immunoglobulin(Ig)G antibody concentration above thresholds |
Countries
United Kingdom
Participant flow
Recruitment details
Healthy female participants aged 18 to 40 years were recruited in a Phase 1 unit from January 2019 and the study was completed by October 2019.
Participants by arm
| Arm | Count |
|---|---|
| GBS-NN/NN2 With Alhydrogel® 25 GBS-NN/NN2 with Alhydrogel® containing 25 mcg of each GBS-NN and GBS-NN2 administered by intramuscular injection 2 times with 4 weeks apart | 24 |
| GBS-NN/NN2 With Alhydrogel® 50 GBS-NN/NN2 with Alhydrogel® containing 50 mcg of each GBS-NN and GBS-NN2 administered by intramuscular injection 2 times with 4 weeks apart | 24 |
| Placebo With Alhydrogel® Placebo (buffer with Alhydrogel®) vaccine administered by intramuscular injection 2 times with 4 weeks apart | 12 |
| Total | 60 |
Baseline characteristics
| Characteristic | GBS-NN/NN2 With Alhydrogel® 25 | Total | Placebo With Alhydrogel® | GBS-NN/NN2 With Alhydrogel® 50 |
|---|---|---|---|---|
| Age, Continuous | 29.8 Years STANDARD_DEVIATION 5.36 | 29.7 Years STANDARD_DEVIATION 5.72 | 27.3 Years STANDARD_DEVIATION 5.53 | 30.8 Years STANDARD_DEVIATION 6.04 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 60 Participants | 12 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 23 Participants | 59 Participants | 12 Participants | 24 Participants |
| Region of Enrollment United Kingdom | 24 participants | 60 participants | 12 participants | 24 participants |
| Sex: Female, Male Female | 24 Participants | 60 Participants | 12 Participants | 24 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 24 | 0 / 12 |
| other Total, other adverse events | 17 / 24 | 15 / 24 | 8 / 12 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 | 0 / 12 |
Outcome results
Primary
Number of Participants With Treatment Emergent Adverse Events
Number of Participants with Treatment Emergent Adverse Events
Time frame: 85 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GBS-NN/NN2 With Alhydrogel® 25 | Number of Participants With Treatment Emergent Adverse Events | 17 Participants |
| GBS-NN/NN2 With Alhydrogel® 50 | Number of Participants With Treatment Emergent Adverse Events | 15 Participants |
| Placebo With Alhydrogel® | Number of Participants With Treatment Emergent Adverse Events | 8 Participants |
Secondary
Fold Change in Antibody Concentration
Geometric mean fold change in antibody concentration from Day 1 to Day 85 for each group.
Time frame: Day 1 to Day 85
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| GBS-NN/NN2 With Alhydrogel® 25 | Fold Change in Antibody Concentration | GBS-NN | 127.707 Fold change from Day 1 to Day 85 |
| GBS-NN/NN2 With Alhydrogel® 25 | Fold Change in Antibody Concentration | GBS-NN2 | 169.594 Fold change from Day 1 to Day 85 |
| GBS-NN/NN2 With Alhydrogel® 50 | Fold Change in Antibody Concentration | GBS-NN | 131.526 Fold change from Day 1 to Day 85 |
| GBS-NN/NN2 With Alhydrogel® 50 | Fold Change in Antibody Concentration | GBS-NN2 | 211.303 Fold change from Day 1 to Day 85 |
| Placebo With Alhydrogel® | Fold Change in Antibody Concentration | GBS-NN | 0.951 Fold change from Day 1 to Day 85 |
| Placebo With Alhydrogel® | Fold Change in Antibody Concentration | GBS-NN2 | 0.946 Fold change from Day 1 to Day 85 |
Comparison: Adjusted geometric mean fold increase from Day 1 to Day 85: adjusted geometric mean ratio GBS-NN/NN2 25mcg/placebop-value: <0.0001ANOVA
Comparison: Adjusted geometric mean fold increase from Day 1 to Day 85: adjusted geometric mean ratio GBS-NN/NN2 50mcg/placebop-value: <0.0001ANOVA
Secondary
Immunoglobulin(Ig)G Antibody Concentration
Adjusted geometric mean concentration (GMC)
Time frame: Day 85
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| GBS-NN/NN2 With Alhydrogel® 25 | Immunoglobulin(Ig)G Antibody Concentration | GBS-NN | 15.2 Adjusted GMC mcg/mL |
| GBS-NN/NN2 With Alhydrogel® 25 | Immunoglobulin(Ig)G Antibody Concentration | GBS-NN2 | 24.0 Adjusted GMC mcg/mL |
| GBS-NN/NN2 With Alhydrogel® 50 | Immunoglobulin(Ig)G Antibody Concentration | GBS-NN | 17.1 Adjusted GMC mcg/mL |
| GBS-NN/NN2 With Alhydrogel® 50 | Immunoglobulin(Ig)G Antibody Concentration | GBS-NN2 | 29.9 Adjusted GMC mcg/mL |
| Placebo With Alhydrogel® | Immunoglobulin(Ig)G Antibody Concentration | GBS-NN | 0.115 Adjusted GMC mcg/mL |
| Placebo With Alhydrogel® | Immunoglobulin(Ig)G Antibody Concentration | GBS-NN2 | 0.154 Adjusted GMC mcg/mL |
Secondary
Number of Participants With an Immune Response to First and Second Doses
Number of participants with Immunoglobulin(Ig)G antibody concentration above thresholds
Time frame: Day 29 and Day 85
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GBS-NN/NN2 With Alhydrogel® 25 | Number of Participants With an Immune Response to First and Second Doses | GBS-NN2 Day 85 increase above 4mcg/mL | 20 Participants |
| GBS-NN/NN2 With Alhydrogel® 25 | Number of Participants With an Immune Response to First and Second Doses | GBS-NN2 Day 85 increase above 8mcg/mL | 18 Participants |
| GBS-NN/NN2 With Alhydrogel® 25 | Number of Participants With an Immune Response to First and Second Doses | GBS-NN2 Day 29 increase above 1mcg/mL | 20 Participants |
| GBS-NN/NN2 With Alhydrogel® 25 | Number of Participants With an Immune Response to First and Second Doses | GBS-NN Day 29 increase above 8mcg/mL | 13 Participants |
| GBS-NN/NN2 With Alhydrogel® 25 | Number of Participants With an Immune Response to First and Second Doses | GBS-NN Day 85 increase above 1mcg/mL | 23 Participants |
| GBS-NN/NN2 With Alhydrogel® 25 | Number of Participants With an Immune Response to First and Second Doses | GBS-NN Day 85 increase above 2mcg/mL | 20 Participants |
| GBS-NN/NN2 With Alhydrogel® 25 | Number of Participants With an Immune Response to First and Second Doses | GBS-NN Day 29 increase above 1mcg/mL | 19 Participants |
| GBS-NN/NN2 With Alhydrogel® 25 | Number of Participants With an Immune Response to First and Second Doses | GBS-NN2 Day 29 increase above 2mcg/mL | 18 Participants |
| GBS-NN/NN2 With Alhydrogel® 25 | Number of Participants With an Immune Response to First and Second Doses | GBS-NN Day 29 increase above 4mcg/mL | 17 Participants |
| GBS-NN/NN2 With Alhydrogel® 25 | Number of Participants With an Immune Response to First and Second Doses | GBS-NN2 Day 29 increase above 4mcg/mL | 17 Participants |
| GBS-NN/NN2 With Alhydrogel® 25 | Number of Participants With an Immune Response to First and Second Doses | GBS-NN Day 85 increase above 4mcg/mL | 20 Participants |
| GBS-NN/NN2 With Alhydrogel® 25 | Number of Participants With an Immune Response to First and Second Doses | GBS-NN2 Day 29 increase above 8mcg/mL | 16 Participants |
| GBS-NN/NN2 With Alhydrogel® 25 | Number of Participants With an Immune Response to First and Second Doses | GBS-NN2 Day 85 increase above 1mcg/mL | 23 Participants |
| GBS-NN/NN2 With Alhydrogel® 25 | Number of Participants With an Immune Response to First and Second Doses | GBS-NN Day 29 increase above 2mcg/mL | 19 Participants |
| GBS-NN/NN2 With Alhydrogel® 25 | Number of Participants With an Immune Response to First and Second Doses | GBS-NN2 Day 85 increase above 2mcg/mL | 22 Participants |
| GBS-NN/NN2 With Alhydrogel® 25 | Number of Participants With an Immune Response to First and Second Doses | GBS-NN Day 85 increase above 8mcg/mL | 18 Participants |
| GBS-NN/NN2 With Alhydrogel® 50 | Number of Participants With an Immune Response to First and Second Doses | GBS-NN2 Day 29 increase above 8mcg/mL | 18 Participants |
| GBS-NN/NN2 With Alhydrogel® 50 | Number of Participants With an Immune Response to First and Second Doses | GBS-NN Day 85 increase above 8mcg/mL | 20 Participants |
| GBS-NN/NN2 With Alhydrogel® 50 | Number of Participants With an Immune Response to First and Second Doses | GBS-NN2 Day 29 increase above 2mcg/mL | 22 Participants |
| GBS-NN/NN2 With Alhydrogel® 50 | Number of Participants With an Immune Response to First and Second Doses | GBS-NN2 Day 85 increase above 8mcg/mL | 22 Participants |
| GBS-NN/NN2 With Alhydrogel® 50 | Number of Participants With an Immune Response to First and Second Doses | GBS-NN Day 29 increase above 2mcg/mL | 20 Participants |
| GBS-NN/NN2 With Alhydrogel® 50 | Number of Participants With an Immune Response to First and Second Doses | GBS-NN Day 29 increase above 4mcg/mL | 17 Participants |
| GBS-NN/NN2 With Alhydrogel® 50 | Number of Participants With an Immune Response to First and Second Doses | GBS-NN Day 85 increase above 4mcg/mL | 21 Participants |
| GBS-NN/NN2 With Alhydrogel® 50 | Number of Participants With an Immune Response to First and Second Doses | GBS-NN2 Day 85 increase above 4mcg/mL | 22 Participants |
| GBS-NN/NN2 With Alhydrogel® 50 | Number of Participants With an Immune Response to First and Second Doses | GBS-NN Day 29 increase above 8mcg/mL | 13 Participants |
| GBS-NN/NN2 With Alhydrogel® 50 | Number of Participants With an Immune Response to First and Second Doses | GBS-NN2 Day 29 increase above 1mcg/mL | 22 Participants |
| GBS-NN/NN2 With Alhydrogel® 50 | Number of Participants With an Immune Response to First and Second Doses | GBS-NN2 Day 29 increase above 4mcg/mL | 18 Participants |
| GBS-NN/NN2 With Alhydrogel® 50 | Number of Participants With an Immune Response to First and Second Doses | GBS-NN Day 85 increase above 1mcg/mL | 23 Participants |
| GBS-NN/NN2 With Alhydrogel® 50 | Number of Participants With an Immune Response to First and Second Doses | GBS-NN Day 29 increase above 1mcg/mL | 23 Participants |
| GBS-NN/NN2 With Alhydrogel® 50 | Number of Participants With an Immune Response to First and Second Doses | GBS-NN2 Day 85 increase above 1mcg/mL | 23 Participants |
| GBS-NN/NN2 With Alhydrogel® 50 | Number of Participants With an Immune Response to First and Second Doses | GBS-NN Day 85 increase above 2mcg/mL | 23 Participants |
| GBS-NN/NN2 With Alhydrogel® 50 | Number of Participants With an Immune Response to First and Second Doses | GBS-NN2 Day 85 increase above 2mcg/mL | 22 Participants |
| Placebo With Alhydrogel® | Number of Participants With an Immune Response to First and Second Doses | GBS-NN Day 85 increase above 2mcg/mL | 0 Participants |
| Placebo With Alhydrogel® | Number of Participants With an Immune Response to First and Second Doses | GBS-NN Day 29 increase above 1mcg/mL | 0 Participants |
| Placebo With Alhydrogel® | Number of Participants With an Immune Response to First and Second Doses | GBS-NN Day 29 increase above 2mcg/mL | 0 Participants |
| Placebo With Alhydrogel® | Number of Participants With an Immune Response to First and Second Doses | GBS-NN Day 85 increase above 4mcg/mL | 0 Participants |
| Placebo With Alhydrogel® | Number of Participants With an Immune Response to First and Second Doses | GBS-NN Day 85 increase above 8mcg/mL | 0 Participants |
| Placebo With Alhydrogel® | Number of Participants With an Immune Response to First and Second Doses | GBS-NN2 Day 29 increase above 1mcg/mL | 0 Participants |
| Placebo With Alhydrogel® | Number of Participants With an Immune Response to First and Second Doses | GBS-NN2 Day 29 increase above 2mcg/mL | 0 Participants |
| Placebo With Alhydrogel® | Number of Participants With an Immune Response to First and Second Doses | GBS-NN2 Day 29 increase above 4mcg/mL | 0 Participants |
| Placebo With Alhydrogel® | Number of Participants With an Immune Response to First and Second Doses | GBS-NN2 Day 29 increase above 8mcg/mL | 0 Participants |
| Placebo With Alhydrogel® | Number of Participants With an Immune Response to First and Second Doses | GBS-NN2 Day 85 increase above 1mcg/mL | 0 Participants |
| Placebo With Alhydrogel® | Number of Participants With an Immune Response to First and Second Doses | GBS-NN2 Day 85 increase above 2mcg/mL | 0 Participants |
| Placebo With Alhydrogel® | Number of Participants With an Immune Response to First and Second Doses | GBS-NN2 Day 85 increase above 4mcg/mL | 0 Participants |
| Placebo With Alhydrogel® | Number of Participants With an Immune Response to First and Second Doses | GBS-NN2 Day 85 increase above 8mcg/mL | 0 Participants |
| Placebo With Alhydrogel® | Number of Participants With an Immune Response to First and Second Doses | GBS-NN Day 29 increase above 4mcg/mL | 0 Participants |
| Placebo With Alhydrogel® | Number of Participants With an Immune Response to First and Second Doses | GBS-NN Day 29 increase above 8mcg/mL | 0 Participants |
| Placebo With Alhydrogel® | Number of Participants With an Immune Response to First and Second Doses | GBS-NN Day 85 increase above 1mcg/mL | 0 Participants |
Secondary
Seroconversion Rate
4-fold increase in Immunoglobulin(Ig)G antibody concentration
Time frame: Day 85
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GBS-NN/NN2 With Alhydrogel® 25 | Seroconversion Rate | GBS-NN | 23 Participants |
| GBS-NN/NN2 With Alhydrogel® 25 | Seroconversion Rate | GBS-NN2 | 23 Participants |
| GBS-NN/NN2 With Alhydrogel® 50 | Seroconversion Rate | GBS-NN | 23 Participants |
| GBS-NN/NN2 With Alhydrogel® 50 | Seroconversion Rate | GBS-NN2 | 23 Participants |
| Placebo With Alhydrogel® | Seroconversion Rate | GBS-NN | 0 Participants |
| Placebo With Alhydrogel® | Seroconversion Rate | GBS-NN2 | 0 Participants |