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This is is a study of a parenteral rotavirus vaccine (P2-VP8 subunit rotavirus vaccine). The study will examine the safety and immunogenicity of this vaccine first in healthy South African toddlers. If the safety profile is deemed appropriate, the study will continue to explore the safety and immunogenicity of the vaccine in healthy South African infants.
The primary safety hypothesis is that the P2-VP8 subunit rotavirus vaccine is safe and well-tolerated in healthy toddlers and infants. The primary immunogenicity hypothesis is that the P2-VP8 subunit rotavirus vaccine is immunogenic in infant participants and will induce an immune response in at least 80% of participants in at least one of the study groups.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort A P2-VP8 30 mcg | Experimental | Cohort A toddlers (24-35 mo) receiving P2-VP8 Subunit Vaccine (30 mcg) |
|
| Cohort A Placebo | Placebo Comparator | Cohort A toddlers (24-35 mo) |
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| Cohort A P2-VP8 60 mcg | Experimental | Cohort A toddlers (24-35 mo) receiving high dose P2-VP8 Subunit Vaccine (60mcg) |
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| Cohort B P2-VP8 10mcg | Experimental | Cohort B infants receiving P2-VP8 Subunit Vaccine (10mcg) |
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| Cohort B placebo | Placebo Comparator | Cohort B infants aged 6 to < 8 weeks receiving placebo |
|
| Cohort B P2-VP8 30mcg | Experimental | Cohort B infants aged 6 to < 8 weeks receiving P2-VP8 Subunit Vaccine (30mcg) |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| P2-VP8 Subunit Vaccine 10mcg | Biological | 10 mcg |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Vaccine Induced Reactions | Maximum severity of all local reactions or systemic reactogenicity after any vaccination | 7 days following each dose |
| Number of Participants With Serious Adverse Events | Number of participants experiencing a Serious Adverse Event within 28 days of a vaccination and at any time during the study | within 28 days of a study dose and at any time |
| Number of Participants Reporting Any Non-Serious Adverse Event | all adverse events will be recorded over the duration of the 6 month follow up period. | 6 mo following first vaccination |
| Number/Percentage of Infant Participants With Anti-P2-VP8 IgA to P[8] Seroresponse. | Seroresponse is defined as 4 fold rise in Geometric Mean Titer (GMT) between pre-(baseline) and post vaccination (4 weeks after third vaccination). Confidence intervals are displayed as percentages. | Baseline to day 84 |
| Number/Percentage of Infants With Anti-P2-VP8 IgG to P[8] Seroresponses | Seroresponse is defined as 4 fold rise in Geometric Mean Titer (GMT) between pre-(baseline) and post vaccination (4 weeks after third injection).An unadjusted serioresponse was defined as an increase of 4 times or more in titers between baseline and 4 weeks after the 3rd injection. Adjusted IgG and neutralizing antibody post injection titres accounted for the decay in maternal antibodies using the half-life calculated from participants in the placebo group with detectable baseline titers higher than those at the post injection visit. | Baseline to day 84 |
| Number/Percentage of Infants With Neutralizing Antibody Response to WA Strain (G1[P8]) |
| Measure | Description | Time Frame |
|---|---|---|
| Rotavirus Shedding After Administration of Rotarix in Infants Receiving 3 Doses of Vaccine or Placebo. | Percent of infants who shed rotavirus at any timepoint after receiving 3 doses of study vaccine and one dose of Rotarix. Infants received Rotarix vaccination beginning on Day 84. Stool specimens were collected from these infants on the 5th, 7th and 9th day following first administration of Rotarix. This test was performed as a novel functional assessment of the ability to suppress local gut multiplication of the vaccine strain contained in Rotarix. |
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Inclusion Criteria:
healthy infants/toddlers as established by medical history and clinical examination before entering study
age:
parental ability and willingness to provide informed consent
parental intention to remain in the area with the child during the study period.
Exclusion Criteria:
Presence of fever on the day of enrollment
Acute disease at the time of enrollment
Concurrent participation in another clinical trial throughout the entire timeframe for this study
Presence of malnutrition or any systemic disorder (cardiovascular, pulmonary, hepatic, renal, gastrointestinal, hematological, endocrine, immunological, dermatological, neurological, cancer or autoimmune disease) as determined by medical history and/or physical examination that would compromise the participant's health or is likely to result in nonconformance to the protocol
For infant cohort, history of premature birth (<37 weeks gestation)
History of congenital abdominal disorders, intussusception, or abdominal surgery
Known or suspected impairment of immunological function based on medical history and physical examination
For infant cohort only, prior receipt of rotavirus vaccine
A known sensitivity or allergy to any components of the study vaccine
History of anaphylactic reaction
Major congenital or genetic defect
Participant's parents not able, available or willing to accept active weekly follow-up by the study staff
Has received any immunoglobulin therapy and/or blood products since birth or planned administration during the study period
History of chronic administration (defined as more than 14 days) of immunosuppressant medications, including corticosteroids. Infants on inhaled or topical steroids may be permitted to participate in the study
Any medical condition in the parents/infant that, in the judgment of the investigator, would interfere with or serves as a contraindication to protocol adherence or a participant's parents' ability to give informed consent
HIV infection
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| Name | Affiliation | Role |
|---|---|---|
| Michelle Groome | SAMRC Respiratory and Meningeal Pathogen Research Unit | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Respiratory and Meningeal Pathogens Research Unit (RMPRU) | Johannesburg | Gauteng | 2013 | South Africa |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32734176 | Derived | Koen A, Jose L, Madhi SA, Fix A, Cryz S, Groome MJ. Neutrophil Counts in Healthy South African Infants: Implications for Enrollment and Adverse Event Grading in Clinical Trials in an African Setting. J Pediatr X. 2019 Spring;1:100005. doi: 10.1016/j.ympdx.2019.100005. | |
| 28483414 | Derived | Groome MJ, Koen A, Fix A, Page N, Jose L, Madhi SA, McNeal M, Dally L, Cho I, Power M, Flores J, Cryz S. Safety and immunogenicity of a parenteral P2-VP8-P[8] subunit rotavirus vaccine in toddlers and infants in South Africa: a randomised, double-blind, placebo-controlled trial. Lancet Infect Dis. 2017 Aug;17(8):843-853. doi: 10.1016/S1473-3099(17)30242-6. Epub 2017 May 5. |
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Age de-escalation, dose-escalation study enrolling healthy toddlers and infants between 17 March and 29 September 2014 at a single site in South Africa.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort A Placebo | Healthy toddlers aged 2 to <3 months receiving placebo |
| FG001 | Cohort A 10 mcg P2-VP8 | Healthy toddlers 2 to <3 yrs of age receiving low dose P2-VP8 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Cohort B1 P2-VP8 60mcg | Experimental | Cohort B1 Infants aged 6 to < 8 weeks receiving P2-VP8 Subunit Vaccine (60mcg) |
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| Cohort A P2-VP8 10mcg | Experimental | Cohort A toddlers (24-35 mo) receiving P2VP8 Subunit Vaccine (10mcg) |
|
| P2-VP8 Subunit Vaccine 30 mcg | Biological | 30 mcg |
|
| P2-VP8 Subunit Vaccine 60mcg | Biological | 60 mcg |
|
| Placebo | Other |
|
Seroresponse is defined as 4 fold rise in Geometric Mean Titer (GMT) between pre-(baseline) and post vaccination (4 weeks after third injection).An unadjusted serioresponse was defined as an increase of 4 times or more in titers between baseline and 4 weeks after the 3rd injection. Adjusted IgG and neutralizing antibody post injection titres accounted for the decay in maternal antibodies using the half-life calculated from participants in the placebo group with detectable baseline titers higher than those at the post injection visit. |
| Baseline to Day 84 |
| Rotarix vaccination on Day 84 to day 91 |
| FG002 | Cohort A 30 mcg P2-VP8 | Healthy toddlers aged 2 to <3 yrs receiving an intermediate dose of P2-VP8 |
| FG003 | Cohort A 60 mcg P2-VP8 | Healthy toddlers aged 2 to < 3 yrs receiving high dose P2-PV8 |
| FG004 | Cohort B Placebo | Healthy Infants aged 6 to <8 weeks receiving placebo |
| FG005 | Cohort B 10 mcg P2-VP8 | Healthy Infants aged 6 to <8 weeks receiving low dose P2-VP8 |
| FG006 | Cohort B 30 mcg P2-VP8 | Healthy Infants aged 6 to <8 weeks of age receiving a medium dose of P2-VP8 |
| FG007 | Cohort B 60 mcg P2-VP8 | Healthy Infants aged 6 to <8 weeks receiving high dose of P2-VP8 |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort A Placebo | Healthy toddlers aged 2 to < 3 years receiving placebo |
| BG001 | Cohort A 10 mcg P2-VP8 | Healthy toddlers aged 2 to < 3 years receiving low dose P2-VP8 |
| BG002 | Cohort A 30 mcg P2-VP8 | Healthy toddlers aged 2 to < 3 years receiving Medium Dose Ps-VP9 |
| BG003 | Cohort A 60 mcg P2-VP8 | Healthy toddlers aged 2 to < 3 years receiving High Dose P2-VP8 |
| BG004 | Cohort B Placebo | Healthy Infants aged 6 to <8 weeks receiving placeblo |
| BG005 | Cohort B 10 mcg P2-VP8 | Healthy Infants aged 6 to <8 weeks receiving Low Dose P2-VP8 |
| BG006 | Cohort B 30 mcg P2-VP8 | Healthy Infants aged 6 to <8 weeks receiving Medium Dose P2-VP8 |
| BG007 | Cohort B 60 mcg P2-VP8 | Healthy Infants aged 6 to <8 weeks receiving High Dose P2-VP8 |
| BG008 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Full Range | weeks |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
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| 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 | Number of Participants With Vaccine Induced Reactions | Maximum severity of all local reactions or systemic reactogenicity after any vaccination | Posted | Count of Participants | Participants | 7 days following each dose |
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| Primary | Number of Participants With Serious Adverse Events | Number of participants experiencing a Serious Adverse Event within 28 days of a vaccination and at any time during the study | All subjects that received at least one dose of P2-VP8 vaccine or placebo | Posted | Count of Participants | Participants | within 28 days of a study dose and at any time |
| |||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | Number of Participants Reporting Any Non-Serious Adverse Event | all adverse events will be recorded over the duration of the 6 month follow up period. | Posted | Count of Participants | Participants | 6 mo following first vaccination |
| ||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | Number/Percentage of Infant Participants With Anti-P2-VP8 IgA to P[8] Seroresponse. | Seroresponse is defined as 4 fold rise in Geometric Mean Titer (GMT) between pre-(baseline) and post vaccination (4 weeks after third vaccination). Confidence intervals are displayed as percentages. | Enrolled infants who received 3 vaccinations and with pre and post-vaccination immunologic parameters measured | Posted | Count of Participants | Participants | Baseline to day 84 |
| |||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | Number/Percentage of Infants With Anti-P2-VP8 IgG to P[8] Seroresponses | Seroresponse is defined as 4 fold rise in Geometric Mean Titer (GMT) between pre-(baseline) and post vaccination (4 weeks after third injection).An unadjusted serioresponse was defined as an increase of 4 times or more in titers between baseline and 4 weeks after the 3rd injection. Adjusted IgG and neutralizing antibody post injection titres accounted for the decay in maternal antibodies using the half-life calculated from participants in the placebo group with detectable baseline titers higher than those at the post injection visit. | Posted | Count of Participants | Participants | Baseline to day 84 |
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| Primary | Number/Percentage of Infants With Neutralizing Antibody Response to WA Strain (G1[P8]) | Seroresponse is defined as 4 fold rise in Geometric Mean Titer (GMT) between pre-(baseline) and post vaccination (4 weeks after third injection).An unadjusted serioresponse was defined as an increase of 4 times or more in titers between baseline and 4 weeks after the 3rd injection. Adjusted IgG and neutralizing antibody post injection titres accounted for the decay in maternal antibodies using the half-life calculated from participants in the placebo group with detectable baseline titers higher than those at the post injection visit. | Enrolled infants who received placebo, 10 mcg, 30 mcg or 60 mcg V2-VP8. | Posted | Count of Participants | Participants | Baseline to Day 84 |
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| Secondary | Rotavirus Shedding After Administration of Rotarix in Infants Receiving 3 Doses of Vaccine or Placebo. | Percent of infants who shed rotavirus at any timepoint after receiving 3 doses of study vaccine and one dose of Rotarix. Infants received Rotarix vaccination beginning on Day 84. Stool specimens were collected from these infants on the 5th, 7th and 9th day following first administration of Rotarix. This test was performed as a novel functional assessment of the ability to suppress local gut multiplication of the vaccine strain contained in Rotarix. | Posted | Count of Participants | Participants | Rotarix vaccination on Day 84 to day 91 |
|
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28 days after any vaccination
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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 | Cohort A Placebo | Healthy toddlers aged 2 to <3 years receiving Placebo | 0 | 5 | 0 | 5 | 2 | 5 |
| EG001 | Cohort A 10 mcg P2-VP8 | Healthy toddlers aged 2 to <3 years receiving Low Dose P2-VP8 | 0 | 13 | 0 | 13 | 7 | 13 |
| EG002 | Cohort A 30 mcg P2-VP8 | Healthy toddlers aged 2 to <3 years receiving Medium Dose P2-VP8 | 0 | 12 | 0 | 12 | 6 | 12 |
| EG003 | Cohort A 60 mcg P2-VP8 | Healthy toddlers aged 2 to <3 years receiving High Dose P2-VP8 | 0 | 12 | 0 | 12 | 8 | 12 |
| EG004 | Cohort B Placebo | Healthy Infants aged 6 to <8 weeks receiving placebo | 0 | 50 | 4 | 50 | 41 | 50 |
| EG005 | Cohort B 10 mcg P2-VP8 | Healthy Infants aged 6 to <8 weeks receiving Low Dose P2-VP8 | 0 | 12 | 0 | 12 | 11 | 12 |
| EG006 | Cohort B 30 mcg P2-VP8 | Healthy Infants aged 6 to <8 weeks receiving Medium Dose P2-VP8 | 0 | 50 | 7 | 50 | 46 | 50 |
| EG007 | Cohort B 60 mcg P2-VP8 | Healthy Infants aged 6 to <8 weeks receiving High Dose P2-VP8 | 2 | 50 | 8 | 50 | 42 | 50 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
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| Acute gastroenteritis | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
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| Pulmonary Tuberculosis | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
| |
| Bronchiolitis | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
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| Staphylococcal impetigo | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
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| Infected cyst | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
| |
| death | General disorders | MedDRA (Unspecified) | Non-systematic Assessment | Death unknown cause |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | MedDRA (Unspecified) | Non-systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
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| Pyrexia | General disorders | MedDRA (Unspecified) | Non-systematic Assessment |
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| Body tinea | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
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| Bronchiolitis | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
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| Candida nappy rash | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
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| Conjuntivitis | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
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| Fungal skin infection | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
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| Gastroenteritis | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
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| Helminthic infection | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
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| Impetigo | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
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| Oral candidiasis | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
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| Otitis media acute | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
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| Varicella | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
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| Viral Rash | Infections and infestations | MedDRA (Unspecified) | Non-systematic Assessment |
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| Soft Tissue Injury | Injury, poisoning and procedural complications | MedDRA (Unspecified) | Non-systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA (Unspecified) | Non-systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
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| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
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| Rhinorrhea | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
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| Dermatitiis | Skin and subcutaneous tissue disorders | MedDRA (Unspecified) | Non-systematic Assessment |
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| Dermatitis diaper | Skin and subcutaneous tissue disorders | MedDRA (Unspecified) | Non-systematic Assessment |
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| Eczema | Skin and subcutaneous tissue disorders | MedDRA (Unspecified) | Non-systematic Assessment |
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| Rash Papular | Skin and subcutaneous tissue disorders | MedDRA (Unspecified) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Michelle J. Groome, MD, PhD | Chris Hani Baragwanath Academic Hospital | +27 11 983 4283 | groomem@rmpru.co.za |
| Male |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
|
| Mild |
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| Moderate |
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| Severe |
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| Life Threatening |
|
Healthy Infants aged 6 to <8 weeks receiving Placebo |
| OG005 | Cohort B 10 mcg P2-VP8 | Healthy Infants aged 6 to <8 weeks receiving Low Dose P2-VP8 |
| OG006 | Cohort B 30 mcg P2-VP8 | Healthy Infants aged 6 to <8 weeks receiving Medium Dose P2-VP8 |
| OG007 | Cohort B 60 mcg P2-VP8 | Healthy Infants aged 6 to <8 weeks receiving High Dose P2-VP8 |
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| OG005 | Cohort B 10 mcg P2-VP8 | Healthy Infants aged 6 to <8 weeks receiving Low Dose P2-VP8 |
| OG006 | Cohort B 30 mcg P2-VP8 | Healthy Infants aged 6 to <8 weeks receiving Medium Dose P2-VP8 |
| OG007 | Cohort B 60 mcg P2-VP8 | Healthy Infants aged 6 to <8 weeks receiving High Dose Infants P2-VP8 |
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| Units | Counts |
|---|---|
| Participants |
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Healthy Infants aged 6 to <8 weeks receiving High Dose P2-VP8
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| Cohort B 60 mcg P2-VP8 |
Healthy Infants aged 6 to <8 weeks receiving High Dose P2-VP8 |
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| Participants |
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