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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| GBS-NN Vaccine | Active Comparator | GBS-NN vaccine administered either adsorbed to Alhydrogel® or alone. |
|
| Sterile dilution buffer with Alhydrogel | Placebo Comparator | The placebo will contain either Alhydrogel® or buffer alone. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GBS-NN vaccine | Biological | Three dose levels will be administered, with and without Alhydrogel® |
|
| Measure | Description | Time Frame |
|---|---|---|
| Part A Number of Participants With Treatment Emergent Adverse Events | Number of Participants with Treatment Emergent Adverse Events | 12 weeks (to Day 85) |
| Part B Number of Participants With Treatment Emergent Adverse Events | Number of Participants with Treatment Emergent Adverse Events | 12 weeks (to Day 85) |
| Measure | Description | Time Frame |
|---|---|---|
| Part A Antibody Concentration | Geometric mean antibody concentration | 12 weeks (Day 85) |
| Part B Antibody Concentration | Geometric mean antibody concentration |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Per Fisher, PM/CEO | MinervaX ApS, Ole Maaløes Vej 3, DK-2200 Copenhagen N, Denmark | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Biokinetic Europ Ltd | Belfast | BT2 7BA | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35243418 | Derived | Pawlowski A, Lannergard J, Gonzalez-Miro M, Cao D, Larsson S, Persson JJ, Kitson G, Darsley M, Rom AL, Hedegaard M, Fischer PB, Johansson-Lindbom B. A group B Streptococcus alpha-like protein subunit vaccine induces functionally active antibodies in humans targeting homotypic and heterotypic strains. Cell Rep Med. 2022 Feb 15;3(2):100511. doi: 10.1016/j.xcrm.2022.100511. eCollection 2022 Feb 15. | |
| 34215454 |
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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.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part A GBS-NN Vaccine 10mcg | GBS-NN 10mcg vaccine administered without Alhydrogel® by intramuscular injection on Day 1 and Day 29 |
| FG001 | Part A GBS-NN Vaccine 50mcg | GBS-NN 50mcg vaccine administered without Alhydrogel® by intramuscular injection on Day 1 and Day 29 |
| FG002 | Part A GBS-NN Vaccine 250mcg | GBS-NN 250mcg vaccine administered without Alhydrogel® by intramuscular injection on Day 1 and Day 29 |
| FG003 | Part A GBS-NN 10mcg Vaccine Administered With Alhydrogel® Adjuvant | GBS-NN 10mcg vaccine administered with Alhydrogel® by intramuscular injection on Day 1 and Day 29 |
| FG004 | Part A GBS-NN 50mcg Vaccine Administered With Alhydrogel® Adjuvant | GBS-NN 50mcg vaccine administered with Alhydrogel® by intramuscular injection on Day 1 and Day 29 |
| FG005 | Part A GBS-NN 250mcg Vaccine Administered With Alhydrogel® Adjuvant | GBS-NN 250mcg vaccine administered with Alhydrogel® by intramuscular injection on Day 1 and Day 29 |
| FG006 | Part A Placebo | Alhydrogel® mixed with dilution buffer or buffer alone administered by intramuscular injection |
| FG007 | Part B GBS-NN Vaccine 50mcg | GBS-NN 50mcg vaccine administered with Alhydrogel® by intramuscular injection on Day 1 and Day 29 |
| FG008 | Part B GBS-NN Vaccine 100mcg 2 Dose Regimen | GBS-NN 100mcg vaccine administered with Alhydrogel® by intramuscular injection on Day 1 and Day 29 |
| FG009 | Part B GBS-NN Vaccine 100mcg Single Dose | GBS-NN 100mcg vaccine administered with Alhydrogel® by intramuscular injection on Day 1 |
| FG010 | Part B Placebo | Alhydrogel® mixed with dilution buffer and administered by intramuscular injection |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Part A GBS-NN Vaccine 10mcg | GBS-NN 10mcg vaccine administered without Alhydrogel® by intramuscular injection on Day 1 and Day 29 |
| BG001 | Part A GBS-NN Vaccine 50mcg | GBS-NN 50mcg vaccine administered without Alhydrogel® by intramuscular injection on Day 1 and Day 29 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Part A Number of Participants With Treatment Emergent Adverse Events | Number of Participants with Treatment Emergent Adverse Events | Posted | Number | participants | 12 weeks (to Day 85) |
|
Part A: to 12 weeks (D85) Part B: to 12 weeks (D85)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part A GBS-NN Vaccine 10mcg | GBS-NN 10mcg vaccine administered without Alhydrogel® by intramuscular injection on Day 1 and Day 29 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Spontaneous abortion | Pregnancy, puerperium and perinatal conditions | MedDRA 19.0 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Injection site pain | General disorders | MedDRA 19.0 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Per Fisher DPhil | MinervaX ApS | +45 20 25 20 38 | pbf@minervax.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 30, 2015 | Nov 30, 2020 | Prot_SAP_000.pdf |
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| 12 weeks (Day 85) |
| Part B Antibody Concentration | Geometric mean antibody concentration | 1 year (Day 365) |
| Part B Number of Participants With Treatment Emergent Adverse Events | Number of Participants with Treatment Emergent Adverse Events | Day 85 to Day 365 |
| Derived |
| Fischer P, Pawlowski A, Cao D, Bell D, Kitson G, Darsley M, Johansson-Lindbom B. Safety and immunogenicity of a prototype recombinant alpha-like protein subunit vaccine (GBS-NN) against Group B Streptococcus in a randomised placebo-controlled double-blind phase 1 trial in healthy adult women. Vaccine. 2021 Jul 22;39(32):4489-4499. doi: 10.1016/j.vaccine.2021.06.046. Epub 2021 Jun 30. |
| BG002 | Part A GBS-NN Vaccine 250mcg | GBS-NN 250mcg vaccine administered without Alhydrogel® by intramuscular injection on Day 1 and Day 29 |
| BG003 | 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 |
| BG004 | 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 |
| BG005 | 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 |
| BG006 | Part A Placebo | Alhydrogel® mixed with dilution buffer or buffer alone administered by intramuscular injection |
| BG007 | Part B GBS-NN Vaccine 50mcg | GBS-NN 50mcg vaccine administered with Alhydrogel® by intramuscular injection on Day 1 and Day 29 |
| BG008 | 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 |
| BG009 | Part B GBS-NN Vacine 100mcg Single Dose | GBS-NN 100mcg vaccine administered with Alhydrogel® by intramuscular injection on Day 1 |
| BG010 | Part B Placebo | Alhydrogel® mixed with dilution buffer and administered by intramuscular injection |
| BG011 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
GBS-NN 250mcg vaccine administered without Alhydrogel® by intramuscular injection on Day 1 and Day 29 |
| OG003 | 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 |
| OG004 | 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 |
| OG005 | 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 |
| OG006 | Part A Placebo | Alhydrogel® mixed with dilution buffer or buffer alone administered by intramuscular injection |
|
|
| Primary | Part B Number of Participants With Treatment Emergent Adverse Events | Number of Participants with Treatment Emergent Adverse Events | Posted | Number | participants | 12 weeks (to Day 85) |
|
|
|
| Secondary | Part A Antibody Concentration | Geometric mean antibody concentration | Posted | Geometric Mean | Full Range | mcg/mL | 12 weeks (Day 85) |
|
|
|
|
| Secondary | Part B Antibody Concentration | Geometric mean antibody concentration | Posted | Geometric Mean | Full Range | mcg/mL | 12 weeks (Day 85) |
|
|
|
|
| Secondary | Part B Antibody Concentration | Geometric mean antibody concentration | Posted | Geometric Mean | Full Range | mcg/mL | 1 year (Day 365) |
|
|
|
|
| Secondary | Part B Number of Participants With Treatment Emergent Adverse Events | Number of Participants with Treatment Emergent Adverse Events | Posted | Number | participants | Day 85 to Day 365 |
|
|
|
| 0 |
| 8 |
| 0 |
| 8 |
| 6 |
| 8 |
| EG001 | Part A GBS-NN Vaccine 50mcg | GBS-NN 50mcg vaccine administered without Alhydrogel® by intramuscular injection on Day 1 and Day 29 | 0 | 8 | 0 | 8 | 5 | 8 |
| EG002 | Part A GBS-NN Vaccine 250mcg | GBS-NN 250mcg vaccine administered without Alhydrogel® by intramuscular injection on Day 1 and Day 29 | 0 | 8 | 0 | 8 | 5 | 8 |
| EG003 | 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 | 0 | 8 | 0 | 8 | 6 | 8 |
| EG004 | 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 | 0 | 8 | 0 | 8 | 8 | 8 |
| EG005 | 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 | 0 | 8 | 0 | 8 | 8 | 8 |
| EG006 | Part A Placebo | Alhydrogel® mixed with dilution buffer or buffer alone administered by intramuscular injection | 0 | 12 | 0 | 12 | 11 | 12 |
| EG007 | Part B GBS-NN Vaccine 50mcg | GBS-NN 50mcg vaccine administered with Alhydrogel® by intramuscular injection on Day 1 and Day 29 | 0 | 45 | 0 | 45 | 41 | 45 |
| EG008 | 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 | 0 | 45 | 0 | 45 | 39 | 45 |
| EG009 | Part B GBS-NN Vacine 100mcg Single Dose | GBS-NN 100mcg vaccine administered with Alhydrogel® by intramuscular injection on Day 1 | 0 | 45 | 0 | 45 | 31 | 45 |
| EG010 | Part B Placebo | Alhydrogel® mixed with dilution buffer and administered by intramuscular injection | 0 | 45 | 1 | 45 | 37 | 45 |
| Headache | Nervous system disorders | MedDRA 19.0 | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 19.0 | Non-systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 19.0 | Non-systematic Assessment |
|
| Dysmenorrhoea | Reproductive system and breast disorders | MedDRA 19.0 | Non-systematic Assessment |
|
| Seasonal allergy | Immune system disorders | MedDRA 19.0 | Non-systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Non-systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Non-systematic Assessment |
|
| Injection site reaction | General disorders | MedDRA 19.0 | Non-systematic Assessment |
|
| Injection site erythema | General disorders | MedDRA 19.0 | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 19.0 | Non-systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 19.0 | Non-systematic Assessment |
|
| Tonsillitis | Infections and infestations | MedDRA 19.0 | Non-systematic Assessment |
|
| Lower respiratory tract infection | Infections and infestations | MedDRA 19.0 | Non-systematic Assessment |
|
| Vulvovaginal candidiasis | Infections and infestations | MedDRA 19.0 | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 19.0 | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 19.0 | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Non-systematic Assessment |
|
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ANOVA repeated measures: In-transformed antibody concentrations as dependent variable; dose level, time, presence of adjuvant and dose*time interaction as fixed effects; subjects as random effects