Infection by Streptococcus Group B
Conditions
Brief summary
Part A: The primary objective is to evaluate the safety and tolerability of a potential vaccine against Group B streptococcus. Part B: To evaluate the long term safety profile of the GBS-NN vaccine up to one year following the first dose.
Detailed description
Part A: Subjects will receive 2 doses of the vaccine, GBS-NN, and will be followed for 12 weeks after the first dose of the vaccine. The following safety endpoints will be evaluated to support this objective: local and systemic reactogenicity; adverse events; laboratory tests; urinalysis; vital signs; 12-Lead ECG parameters; physical examination. In addition hereto, immunological parameters will be evaluated. Part B: Subjects will receive one or 2 doses of GBS-NN, and will be followed for 12 months after the first dose of the vaccine. The following safety endpoints will be evaluated to support this objective: local and systemic reactogenicity; adverse events; laboratory tests; urinalysis; vital signs; 12-Lead ECG parameters; physical examination. In addition hereto, immunological parameters will be evaluated.
Interventions
BIOLOGICALGBS-NN vaccine
Three dose levels will be administered, with and without Alhydrogel®
Sponsors
Minervax ApS
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy adult female volunteers (as determined by medical history, physical examination, laboratory test values, vital signs and electrocardiograms \[ECGs\] at screening) aged 18 - 40 years. 2. Body mass index (BMI) ≥ 18 and ≤ 30 kg/m2. 3. Volunteers weight ≥ 50kg and ≤100kg at screening. 4. Able to voluntarily provide written informed consent to participate in the study. 5. Must understand the purposes and risks of the study and agree to follow the restrictions and schedule of procedures as defined in the protocol. 6. Volunteers must be pre-menopausal. Volunteers who have had a hysterectomy will have pre-menopausal status confirmed by a FSH and oestradiol test. 7. Females of childbearing potential must have a negative pregnancy test at screening (β HCG) and prior to each dose and must be willing to use an adequate and highly effective method of contraception until at least Day 85 of the study. A highly effective method of birth control is defined as one which results in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as sterilisation, implants, injectables, combined oral contraceptives, IUDs (Intrauterine Device), condoms, occlusive caps (cervical/vault caps) with spermicidal foam/gel/ film/cream/suppository. True sexual abstinence is acceptable when this is in line with the preferred and usual lifestyle of the volunteer (periodic abstinence e.g. calendar, ovulation, symptothermal, post-ovulation methods, declaration of abstinence for the duration of the trial, and withdrawal are not acceptable methods of contraception) 8. In Part A: Volunteers must be non-smokers for at least 3 months prior to first studyvaccine administration. In Part B: Volunteers may be light smokers i.e. up to a maximum of 5 cigarettes per day or nicotine equivalent. 9. Must be willing to consent to have data entered into The Over Volunteering Prevention System (TOPS). 10. The volunteer's primary care physician has confirmed within the last 12 months that there is nothing in their medical history that would preclude their enrolment into a clinical trial.
Exclusion criteria
1. Volunteers 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. 2. Pregnant or lactating females. 3. Laboratory values at screening which are deemed to be clinically significant, unless agreed in advance by the Sponsor's Responsible Medic and Principal Investigator. 4. Current or history of drug or alcohol abuse, or a positive alcohol breath test prior to first dosing. 5. Positive for human immunodeficiency virus (HIV), hepatitis B or hepatitis C. 6. Participation in a clinical drug study during the 90 days preceding the initial dose in this study. 7. Any significant illness during the 4 weeks preceding check-in for this study (Day 1). 8. Volunteers with a history of severe allergic reactions after previous vaccination. 9. Volunteers 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. 10. Volunteers receiving immunosuppressive therapy (e.g. systemic steroids, cancer therapies, methotrexate, azathioprine) in the 6 months prior to screening, antibiotics within 10 days of receiving the first dose or taking any short-term medications including over-the-counter preparations, vitamins, herbal and/or mineral supplements 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. 11. Volunteers with tattoos at the proposed site of vaccine administration. 12. Donation of blood or blood products within 90 days prior to vaccine administration. 13. Volunteers who, in the opinion of the Investigator, are unsuitable for participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A Number of Participants With Treatment Emergent Adverse Events | 12 weeks (to Day 85) | Number of Participants with Treatment Emergent Adverse Events |
| Part B Number of Participants With Treatment Emergent Adverse Events | 12 weeks (to Day 85) | Number of Participants with Treatment Emergent Adverse Events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A Antibody Concentration | 12 weeks (Day 85) | Geometric mean antibody concentration |
| Part B Antibody Concentration | 12 weeks (Day 85) | Geometric mean antibody concentration |
| Part B Number of Participants With Treatment Emergent Adverse Events | Day 85 to Day 365 | Number of Participants with Treatment Emergent Adverse Events |
Countries
United Kingdom
Participant flow
Recruitment details
Part A: Healthy females were recruited to receive two doses of either GBS-NN vaccine with or without Alhydrogel® gel adjuvant at three dose levels (10mcg, 50mcg, 250mcg) or placebo. Part B: Doses of 50mcg (2 doses) and 100mcg (1 and 2 doses) were selected from the antibody levels at 8 weeks from Part A and vaccine was administered with Alhydrogel®. Participants were healthy females and did not include participants from Part A. They were followed up for 1 year.
Pre-assignment details
Part A was the dose-finding part of the study and 60 healthy female participants received either 2 doses of GBS-NN 10mcg, 50mcg, 250mcg or placebo (4:1 ratio of active:placebo). Based on the 8 week (Day 57) antibody levels from Part A, 180 healthy female participants in Part B were recruited to receive either 2 doses of GBS-NN 50mcg, 2 doses of GBS-NN 100mcg, 1 dose of GBS-NN 100mcg or placebo (3:1 ratio of active to placebo). Participants in Part A were not allowed to participate In Part B.
Participants by arm
| Arm | Count |
|---|---|
| Part A GBS-NN Vaccine 10mcg GBS-NN 10mcg vaccine administered without Alhydrogel® by intramuscular injection on Day 1 and Day 29 | 8 |
| Part A GBS-NN Vaccine 50mcg GBS-NN 50mcg vaccine administered without Alhydrogel® by intramuscular injection on Day 1 and Day 29 | 8 |
| Part A GBS-NN Vaccine 250mcg GBS-NN 250mcg vaccine administered without Alhydrogel® by intramuscular injection on Day 1 and Day 29 | 8 |
| Part A GBS-NN Vaccine 10mcg With Alhydrogel® Adjuvant GBS-NN 10 mcg vaccine administered with Alhydrogel® by intramuscular injection on Day 1 and Day 29 | 8 |
| Part A GBS-NN Vaccine 50mcg With Alhydrogel® Adjuvant GBS-NN 50mcg vaccine administered with Alhydrogel® by intramuscular injection on Day 1 and Day 29 | 8 |
| Part A GBS-NN Vaccine 250mcg With Alhydrogel® Adjuvant GBS-NN 250mcg vaccine administered with Alhydrogel® by intramuscular injection on Day 1 and Day 29 | 8 |
| Part A Placebo Alhydrogel® mixed with dilution buffer or buffer alone administered by intramuscular injection | 12 |
| Part B GBS-NN Vaccine 50mcg GBS-NN 50mcg vaccine administered with Alhydrogel® by intramuscular injection on Day 1 and Day 29 | 45 |
| Part B GBS-NN Vacine 100mcg 2 Dose Regimen GBS-NN 100mcg vaccine administered with Alhydrogel® by intramuscular injection on Day 1 and Day 29 | 45 |
| Part B GBS-NN Vacine 100mcg Single Dose GBS-NN 100mcg vaccine administered with Alhydrogel® by intramuscular injection on Day 1 | 45 |
| Part B Placebo Alhydrogel® mixed with dilution buffer and administered by intramuscular injection | 45 |
| Total | 240 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Part A GBS-NN Vaccine 10mcg | Total | Part B Placebo | Part B GBS-NN Vacine 100mcg Single Dose | Part B GBS-NN Vacine 100mcg 2 Dose Regimen | Part B GBS-NN Vaccine 50mcg | Part A Placebo | Part A GBS-NN Vaccine 250mcg With Alhydrogel® Adjuvant | Part A GBS-NN Vaccine 50mcg With Alhydrogel® Adjuvant | Part A GBS-NN Vaccine 10mcg With Alhydrogel® Adjuvant | Part A GBS-NN Vaccine 250mcg | Part A GBS-NN Vaccine 50mcg |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 28.6 years STANDARD_DEVIATION 4.8 | 29.5 years STANDARD_DEVIATION 6.3 | 28.7 years STANDARD_DEVIATION 6.5 | 29.4 years STANDARD_DEVIATION 6.5 | 30.3 years STANDARD_DEVIATION 6 | 29.0 years STANDARD_DEVIATION 6.3 | 28.5 years STANDARD_DEVIATION 6.6 | 30.4 years STANDARD_DEVIATION 5.7 | 31.3 years STANDARD_DEVIATION 4.5 | 28.3 years STANDARD_DEVIATION 7.4 | 30.4 years STANDARD_DEVIATION 5 | 29.3 years STANDARD_DEVIATION 6.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 239 Participants | 44 Participants | 45 Participants | 45 Participants | 45 Participants | 12 Participants | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 239 Participants | 44 Participants | 45 Participants | 45 Participants | 45 Participants | 12 Participants | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 8 Participants |
| Region of Enrollment United Kingdom | 8 participants | 240 participants | 45 participants | 45 participants | 45 participants | 45 participants | 12 participants | 8 participants | 8 participants | 8 participants | 8 participants | 8 participants |
| Sex: Female, Male Female | 8 Participants | 240 Participants | 45 Participants | 45 Participants | 45 Participants | 45 Participants | 12 Participants | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 8 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 12 | 0 / 45 | 0 / 45 | 0 / 45 | 0 / 45 |
| other Total, other adverse events | 6 / 8 | 5 / 8 | 5 / 8 | 6 / 8 | 8 / 8 | 8 / 8 | 11 / 12 | 41 / 45 | 39 / 45 | 31 / 45 | 37 / 45 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 12 | 0 / 45 | 0 / 45 | 0 / 45 | 1 / 45 |
Outcome results
Primary
Part A Number of Participants With Treatment Emergent Adverse Events
Number of Participants with Treatment Emergent Adverse Events
Time frame: 12 weeks (to Day 85)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A GBS-NN Vaccine 10mcg | Part A Number of Participants With Treatment Emergent Adverse Events | 6 participants |
| Part A GBS-NN Vaccine 50mcg | Part A Number of Participants With Treatment Emergent Adverse Events | 5 participants |
| Part A GBS-NN Vaccine 250mcg | Part A Number of Participants With Treatment Emergent Adverse Events | 5 participants |
| Part A GBS-NN Vaccine 10mcg With Alhydrogel® Adjuvant | Part A Number of Participants With Treatment Emergent Adverse Events | 6 participants |
| Part A GBS-NN Vaccine 50mcg With Alhydrogel® Adjuvant | Part A Number of Participants With Treatment Emergent Adverse Events | 8 participants |
| Part A GBS-NN Vaccine 250mcg With Alhydrogel® Adjuvant | Part A Number of Participants With Treatment Emergent Adverse Events | 8 participants |
| Part A Placebo | Part A Number of Participants With Treatment Emergent Adverse Events | 11 participants |
Primary
Part B Number of Participants With Treatment Emergent Adverse Events
Number of Participants with Treatment Emergent Adverse Events
Time frame: 12 weeks (to Day 85)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A GBS-NN Vaccine 10mcg | Part B Number of Participants With Treatment Emergent Adverse Events | 41 participants |
| Part A GBS-NN Vaccine 50mcg | Part B Number of Participants With Treatment Emergent Adverse Events | 39 participants |
| Part A GBS-NN Vaccine 250mcg | Part B Number of Participants With Treatment Emergent Adverse Events | 31 participants |
| Part A GBS-NN Vaccine 10mcg With Alhydrogel® Adjuvant | Part B Number of Participants With Treatment Emergent Adverse Events | 37 participants |
Secondary
Part A Antibody Concentration
Geometric mean antibody concentration
Time frame: 12 weeks (Day 85)
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part A GBS-NN Vaccine 10mcg | Part A Antibody Concentration | 1.977 mcg/mL |
| Part A GBS-NN Vaccine 50mcg | Part A Antibody Concentration | 2.926 mcg/mL |
| Part A GBS-NN Vaccine 250mcg | Part A Antibody Concentration | 7.195 mcg/mL |
| Part A GBS-NN Vaccine 10mcg With Alhydrogel® Adjuvant | Part A Antibody Concentration | 16.864 mcg/mL |
| Part A GBS-NN Vaccine 50mcg With Alhydrogel® Adjuvant | Part A Antibody Concentration | 14.999 mcg/mL |
| Part A GBS-NN Vaccine 250mcg With Alhydrogel® Adjuvant | Part A Antibody Concentration | 25.431 mcg/mL |
| Part A Placebo | Part A Antibody Concentration | 0.199 mcg/mL |
Comparison: The objectives for Part A were to evaluate the effect of adjuvant and to inform the selection of dose levels for Part B. The study was not powered for inter-group comparisons.p-value: 0.0193ANOVA
Secondary
Part B Antibody Concentration
Geometric mean antibody concentration
Time frame: 12 weeks (Day 85)
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part A GBS-NN Vaccine 10mcg | Part B Antibody Concentration | 16.914 mcg/mL |
| Part A GBS-NN Vaccine 50mcg | Part B Antibody Concentration | 15.459 mcg/mL |
| Part A GBS-NN Vaccine 250mcg | Part B Antibody Concentration | 3.035 mcg/mL |
| Part A GBS-NN Vaccine 10mcg With Alhydrogel® Adjuvant | Part B Antibody Concentration | 0.234 mcg/mL |
p-value: <0.0001ANOVA
Secondary
Part B Antibody Concentration
Geometric mean antibody concentration
Time frame: 1 year (Day 365)
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part A GBS-NN Vaccine 10mcg | Part B Antibody Concentration | 4.201 mcg/mL |
| Part A GBS-NN Vaccine 50mcg | Part B Antibody Concentration | 5.934 mcg/mL |
| Part A GBS-NN Vaccine 250mcg | Part B Antibody Concentration | 1.596 mcg/mL |
| Part A GBS-NN Vaccine 10mcg With Alhydrogel® Adjuvant | Part B Antibody Concentration | 0.263 mcg/mL |
p-value: <0.0001ANOVA
Secondary
Part B Number of Participants With Treatment Emergent Adverse Events
Number of Participants with Treatment Emergent Adverse Events
Time frame: Day 85 to Day 365
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A GBS-NN Vaccine 10mcg | Part B Number of Participants With Treatment Emergent Adverse Events | 16 participants |
| Part A GBS-NN Vaccine 50mcg | Part B Number of Participants With Treatment Emergent Adverse Events | 23 participants |
| Part A GBS-NN Vaccine 250mcg | Part B Number of Participants With Treatment Emergent Adverse Events | 22 participants |
| Part A GBS-NN Vaccine 10mcg With Alhydrogel® Adjuvant | Part B Number of Participants With Treatment Emergent Adverse Events | 21 participants |