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The primary objective is to assess the systemic and local safety profile of purified inactivated Japanese Encephalitis Virus (JEV) vaccine IC51 administered in two doses in a 28 days interval up to Month 7 after the first IC51 vaccination in a pediatric population from endemic regions.
Open-label, randomized, active controlled Phase 3 study in children aged ≥ 2 months to < 18 years. Subjects aged ≥ 2 months to < 12 months were randomized in a 2:1 ratio to receive IC51 (0.25 ml dose) or Prevnar® as a safety comparator. Children aged ≥ 12 months to < 3 years and ≥ 12 years to < 18 years were randomized in a 3:1 ratio to receive IC51 (0.25 ml dose < 3 years, 0.5 ml ≥ 12 years) or HAVRIX®720 as safety comparator.
For subjects aged ≥ 3 years to < 12 years, a dose finding run-in phase was performed. A total of 200 subjects were randomized 1:1 to receive either the 0.25 ml or the 0.5 ml dose of IC51, and the appropriate dose was determined based on an interim analysis. After this run-in phase, 300 further children in this age group were randomized 2:1 to receive either 0.5 ml of IC51 or HAVRIX®720.
Immunogenicity was be studied in a subgroup of 30 children aged ≥ 2 months to < 12 months; 125 children aged ≥ 12 months to < 3 years and 140 children ≥ 12 years to < 18 years. For the age group of ≥ 3 to < 12 years immunogenicity was assessed in the 200 children enrolled during the dose-finding run-in phase.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| IC51 0.5 mL | Experimental | Japanese Encephalitis Vaccine 6mcg im. at day 0 and day 28 |
|
| IC51 0.25 mL | Experimental | Japanese Encephalitis Vaccine 3mcg im. at day 0 and day 28 |
|
| Havrix 720 | Active Comparator | Havrix®720 0.5 ml im. at day 0 and month 7 |
|
| Prevnar | Active Comparator | Prevnar 0.5 ml im. at day 0 and day 56 and month 7 or 0.5 ml im. at day 0, day 28 and day56 and month 7-13 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| IC51 Japanese Encephalitis | Biological | 6 mcg or 3 mcg im. at day 0 and day 28 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Rate of Subjects With Serious Adverse Events and Medically Attended Adverse Events Until Day 56 After First Vaccination | Rate of subjects with these types of AEs, comparison vs respective control vaccine stratified by age group: All study participants aged < 1 year: IC51 0.25mL vs. Prevnar; All study participants aged 1 year and above: IC51 0.25 mL or =.5 mL vs. Havrix. | until Day 56 |
| Measure | Description | Time Frame |
|---|---|---|
| Geometric Mean Titers (GMT) for JEV Neutralizing Antibodies | GMT for JEV neutralizing antibodies is presented per dose group rather than age group due to overlapping age groups. IC51 0.25 mL includes subjects aged 2 months to < 12 years; IC51 0.5 mL includes subjects aged ≥ 3 years to < 18 years. | Day 0, 56 and at Month 7 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Vera Kadlecek | Valneva Austria GmbH | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Institute for Tropical Medicine | City of Muntinlupa | Filinvest Corporate City | 1781 | Philippines | ||
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| ID | Title | Description |
|---|---|---|
| FG000 | IC51 0.5 mL | Japanese Encephalitis Vaccine 6mcg i.m. at day 0 and day 28 |
| FG001 | IC51 0.25 mL | Japanese Encephalitis Vaccine 3mcg i.m. at day 0 and day 28 |
| FG002 | Havrix 720 | Havrix®720 0.5 ml i.m. at day 0 and month 7 |
| FG003 | Prevnar | Prevnar 0.5 ml i.m. at day 0 and day 56 and month 7 or 0.5 ml i.m. at day 0, day 28 and day 56 and month 7-13 |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | IC51 0.25 mL | Japanese Encephalitis Vaccine 3mcg i.m. at day 0 and day 28 |
| BG001 | IC51 0.5 mL | Japanese Encephalitis Vaccine 6mcg i.m. at day 0 and day 28 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Number |
| 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 | Rate of Subjects With Serious Adverse Events and Medically Attended Adverse Events Until Day 56 After First Vaccination | Rate of subjects with these types of AEs, comparison vs respective control vaccine stratified by age group: All study participants aged < 1 year: IC51 0.25mL vs. Prevnar; All study participants aged 1 year and above: IC51 0.25 mL or =.5 mL vs. Havrix. | As specified per protocol, safety parameters were compared between treatment groups (i.e. IC51 any dose level versus Havrix or Prevnar), stratified by age. Age was the determining factor of the respective safety comparators Prevnar (<1yrs) and HAVRIX (1+ yrs). Different dose levels of IC51 were grouped for these analyses, to test the hypothesis that events do not occur in higher frequency after vaccination with IC51 compared to vaccination with Prevnar® or Havrix®720. | Posted | Number | 95% Confidence Interval | percentage of participants | until Day 56 |
|
7 months after first 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 | IC51 0.25 mL | Japanese Encephalitis Vaccine 3mcg i.m. at day 0 and day 28 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | MedDRA 13.0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Upper Respiratory Tract Infection | Infections and infestations | MedDRA 13.0 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Manager Clinical Research | Valneva Austria GmbH | +43 1 206 20 | 1175 | katrin.dubischar-kastner@valneva.com |
| ID | Term |
|---|---|
| D004660 | Encephalitis |
| ID | Term |
|---|---|
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D000090862 | Neuroinflammatory Diseases |
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| ID | Term |
|---|---|
| D000069443 | Heptavalent Pneumococcal Conjugate Vaccine |
| ID | Term |
|---|---|
| D022242 | Pneumococcal Vaccines |
| D022541 | Streptococcal Vaccines |
| D001428 | Bacterial Vaccines |
| D014612 | Vaccines |
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| Havrix®720 | Biological | 0.5 ml im. at day 0 and month 7 |
|
| Prevnar | Biological | 0.5 ml im. at day 0 and day 56 and month 7 |
|
| Seroconversion Rate (SCR) at Days 0, 56 and at Month 7 |
Seroconversion was defined as a PRNT50 titer of at least 1:10. SCRs are presented per dose group rather than age group due to overlapping age groups. IC51 0.25 mL includes subjects aged 2 months to < 12 years; IC51 0.5 mL includes subjects aged ≥ 3 years to < 18 years. |
| Days 0, 56 and at Month 7 |
| Rate of Subjects With SAEs and Medically Attended AEs | Rate of subjects with SAEs and medically attended AEs; For this analysis IC51 vaccine recipients are displayed by age group rather than by dose group. This allows comparison of the safety profile of IC51 with the active control for the respective age group: Prevnar for study participants aged >= 2 months to <1 year and Havrix 720 for study participants aged >= 1 year. | up to Month 7 |
| Rate of Subjects With Solicited Local and Systemic AEs | Rate of subjects with solicited local and systemic AEs. Solicited AEs of local and systemic tolerability, i.e., reactions at the injection site or systemic reactions typical for vaccinations, were to be evaluated for 7 consecutive days after each vaccination (except after the HAVRIX®750 and Prevnar® injections at Month 7 [Visit 4]) and recorded in the subject diary. For this analysis IC51 vaccine recipients are displayed by age group rather than by dose group. This allows comparison of the safety profile of IC51 with the active control for the respective age group: Prevnar for study participants aged >= 2 months to <1 year and Havrix 720 for study participants aged >= 1 year. | 7 days post vaccination |
| Rate of Subjects With Unsolicited AEs up to Day 56 and up to Month 7 | Rate of subjects with unsolicited AEs up to Day 56 and up to Month 7; For this analysis IC51 vaccine recipients are displayed by age group rather than by dose group. This allows comparison of the safety profile of IC51 with the active control for the respective age group: Prevnar for study participants aged >= 2 months to <1 year and Havrix 720 for study participants aged >= 1 year. | Day 56 and up to Month 7 |
| Rate of Subjects With Abnormal Laboratory Parameters | Rate of subjects with abnormal laboratory parameters clinically significant results are shown below | Day 56 and Month 7 |
| Department of Pediatrics, UP-Philippine General Hospital |
| Manila |
| 1000 |
| Philippines |
| Death |
|
| Lost to Follow-up |
|
| Adverse Event |
|
| relocation |
|
| further blood extraction |
|
| positive to anti-HCV |
|
| BG002 | Havrix 720 | Havrix®720 0.5 ml i.m. at day 0 and month 7 |
| BG003 | Prevnar | Prevnar 0.5 ml i.m. at day 0 and day 56 and month 7 or 0.5 ml i.m. at day 0, day 28 and day56 and month 7-13 |
| BG004 | Total | Total of all reporting groups |
| participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
IC51 Japanese Encephalitis: 6 mcg or 3 mcg im. at day 0 and day 28 |
| OG001 | Havrix 720 | Havrix®720 0.5 ml im. at day 0 and month 7; active comparator for subjects aged > 1 year |
| OG002 | IC51, Subjects Aged >= 2 Months to <1 Year | Japanese Encephalitis Vaccine 3mcg im. at day 0 and day 28 |
| OG003 | Prevnar | Active comparator in subjects aged ≥ 2 months to < 1 year:
|
|
|
|
| Secondary | Geometric Mean Titers (GMT) for JEV Neutralizing Antibodies | GMT for JEV neutralizing antibodies is presented per dose group rather than age group due to overlapping age groups. IC51 0.25 mL includes subjects aged 2 months to < 12 years; IC51 0.5 mL includes subjects aged ≥ 3 years to < 18 years. | Intent-to-treat Population: all subjects randomized into the immunogenicity subgroup, who received at least 1 vaccination. Subjects were analyzed according to the treatment group to which they were randomized rather than by the actual vaccine they received. | Posted | Geometric Mean | Standard Deviation | Geometric Mean Titer | Day 0, 56 and at Month 7 |
|
|
|
| Secondary | Seroconversion Rate (SCR) at Days 0, 56 and at Month 7 | Seroconversion was defined as a PRNT50 titer of at least 1:10. SCRs are presented per dose group rather than age group due to overlapping age groups. IC51 0.25 mL includes subjects aged 2 months to < 12 years; IC51 0.5 mL includes subjects aged ≥ 3 years to < 18 years. | "number analyzed" is dependent on number of serum samples available for testing | Posted | Number | 95% Confidence Interval | percentage of participants | Days 0, 56 and at Month 7 |
|
|
|
| Secondary | Rate of Subjects With SAEs and Medically Attended AEs | Rate of subjects with SAEs and medically attended AEs; For this analysis IC51 vaccine recipients are displayed by age group rather than by dose group. This allows comparison of the safety profile of IC51 with the active control for the respective age group: Prevnar for study participants aged >= 2 months to <1 year and Havrix 720 for study participants aged >= 1 year. | As specified per protocol, safety parameters were compared between treatment groups (i.e. IC51 any dose level versus Havrix or Prevnar), stratified by age. Age was the determining factor of the respective safety comparators Prevnar (<1yrs) and HAVRIX (1+ yrs). Different dose levels of IC51 were grouped for these analyses, to test the hypothesis that events do not occur in higher frequency after vaccination with IC51 compared to vaccination with Prevnar® or Havrix®720. | Posted | Number | 95% Confidence Interval | percentage of participants | up to Month 7 |
|
|
|
| Secondary | Rate of Subjects With Solicited Local and Systemic AEs | Rate of subjects with solicited local and systemic AEs. Solicited AEs of local and systemic tolerability, i.e., reactions at the injection site or systemic reactions typical for vaccinations, were to be evaluated for 7 consecutive days after each vaccination (except after the HAVRIX®750 and Prevnar® injections at Month 7 [Visit 4]) and recorded in the subject diary. For this analysis IC51 vaccine recipients are displayed by age group rather than by dose group. This allows comparison of the safety profile of IC51 with the active control for the respective age group: Prevnar for study participants aged >= 2 months to <1 year and Havrix 720 for study participants aged >= 1 year. | As specified per protocol, safety parameters were compared between treatment groups (i.e. IC51 any dose level versus Havrix or Prevnar), stratified by age. Age was the determining factor of the respective safety comparators Prevnar (<1yrs) and HAVRIX (1+ yrs). Different dose levels of IC51 were grouped for these analyses, to test the hypothesis that events do not occur in higher frequency after vaccination with IC51 compared to vaccination with Prevnar® or Havrix®720. | Posted | Number | 95% Confidence Interval | percentage of participants | 7 days post vaccination |
|
|
|
| Secondary | Rate of Subjects With Unsolicited AEs up to Day 56 and up to Month 7 | Rate of subjects with unsolicited AEs up to Day 56 and up to Month 7; For this analysis IC51 vaccine recipients are displayed by age group rather than by dose group. This allows comparison of the safety profile of IC51 with the active control for the respective age group: Prevnar for study participants aged >= 2 months to <1 year and Havrix 720 for study participants aged >= 1 year. | As specified per protocol, safety parameters were compared between treatment groups (i.e. IC51 any dose level versus Havrix or Prevnar), stratified by age. Age was the determining factor of the respective safety comparators Prevnar (<1yrs) and HAVRIX (1+ yrs). Different dose levels of IC51 were grouped for these analyses, to test the hypothesis that events do not occur in higher frequency after vaccination with IC51 compared to vaccination with Prevnar® or Havrix®720. | Posted | Number | 95% Confidence Interval | percentage of participants | Day 56 and up to Month 7 |
|
|
|
| Secondary | Rate of Subjects With Abnormal Laboratory Parameters | Rate of subjects with abnormal laboratory parameters clinically significant results are shown below | Urinalysis Evaluations were not mandatory unless the subject was at least 12 years old at V0. | Posted | Number | participants | Day 56 and Month 7 |
|
|
|
| 16 |
| 871 |
| 691 |
| 871 |
| EG001 | IC51 0.5 mL | Japanese Encephalitis Vaccine 6mcg i.m. at day 0 and day 28 | 7 | 540 | 300 | 540 |
| EG002 | Havrix 720 | Havrix®720 0.5 ml i.m. at day 0 and month 7 | 10 | 394 | 252 | 394 |
| EG003 | Prevnar | Prevnar 0.5 ml i.m. at day 0 and day 56 and month 7 or 0.5 ml i.m. at day 0, day 28 and day 56 and month 7-13 | 1 | 64 | 57 | 64 |
| Febrile Convulsion | Nervous system disorders | MedDRA 13.0 |
|
| Bronchopneumonia | Infections and infestations | MedDRA 13.0 |
|
| Dengue Fever | Infections and infestations | MedDRA 13.0 |
|
| Gastroenteritis | Infections and infestations | MedDRA 13.0 |
|
| Cellulitis | Infections and infestations | MedDRA 13.0 |
|
| Hepatitis A | Infections and infestations | MedDRA 13.0 |
|
| Meningitis Bacterial | Infections and infestations | MedDRA 13.0 |
|
| Pharyngotonsillitis | Infections and infestations | MedDRA 13.0 |
|
| Typhoid Fever | Infections and infestations | MedDRA 13.0 |
|
| Upper Respiratory Tract Infection | Infections and infestations | MedDRA 13.0 |
|
| Urinary Tract Infection | Infections and infestations | MedDRA 13.0 |
|
| Haematoma | Vascular disorders | MedDRA 13.0 |
|
| Kawasaki´s Disease | Vascular disorders | MedDRA 13.0 |
|
| Disseminated Intravascular Coagulation | Blood and lymphatic system disorders | MedDRA 13.0 |
|
| Familial Periodic Paralysis | Congenital, familial and genetic disorders | MedDRA 13.0 |
|
| Strabismus | Eye disorders | MedDRA 13.0 |
|
| Injury | Injury, poisoning and procedural complications | MedDRA 13.0 |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 13.0 |
|
| Stillbirth | Pregnancy, puerperium and perinatal conditions | MedDRA 13.0 |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 13.0 |
|
| Gastroenteritis | Infections and infestations | MedDRA 13.0 |
|
| Nasopharyngitis | Infections and infestations | MedDRA 13.0 |
|
| Pyrexia | General disorders | MedDRA 13.0 |
|
| Heat Rash | Skin and subcutaneous tissue disorders | MedDRA 13.0 |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 13.0 |
|
| Rhinitis | Infections and infestations | MedDRA 13.0 |
|
| Injection Site Pain | General disorders | MedDRA 13.0 | Systematic Assessment | pain without touching, solicited local |
|
| Tenderness | General disorders | MedDRA 13.0 | Systematic Assessment | pain upon touching, solicited local |
|
| Hardening | General disorders | MedDRA 13.0 | Systematic Assessment | solicited local |
|
| Swelling | General disorders | MedDRA 13.0 | Systematic Assessment | solicited local |
|
| Redness | General disorders | MedDRA 13.0 | Systematic Assessment | solicited local |
|
| Flu-like symptoms | General disorders | MedDRA 13.0 | Systematic Assessment | solicited systemic |
|
| Headache | Nervous system disorders | MedDRA 13.0 | Systematic Assessment | solicited systemic |
|
| Fever | General disorders | MedDRA 13.0 | Systematic Assessment | solicited systemic |
|
| Irritability | General disorders | MedDRA 13.0 | Systematic Assessment | solicited systemic |
|
| Vomiting | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment | solicited systemic |
|
| Diarrhea | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment | solicited systemic |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 13.0 | Systematic Assessment | solicited systemic |
|
| Loss of appetite | Metabolism and nutrition disorders | MedDRA 13.0 | Systematic Assessment | solicited systemic |
|
| Excessive Fatigue | General disorders | MedDRA 13.0 | Systematic Assessment | solicited systemic |
|
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| D001688 |
| Biological Products |
| D045424 | Complex Mixtures |
| D017778 | Vaccines, Combined |
| Month 7 |
|
| Day 56 |
|
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| Month 7 |
|
|
| Rate of subjects with medically attended AE |
|
| Month 7 |
|
|
| Hemoglobin Month 7 |
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| Hematocrit Day 56 |
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| Hematocrit Month 7 |
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| White Blood Cells Day 56 |
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| White Blood Cells Month 7 |
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| Platelets Day 56 |
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| Platelets Month 7 |
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| Potassium Day 56 |
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| Potassium Month 7 |
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| Calcium Day 56 |
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| Calcium Month 7 |
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| AST Day 56 |
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| AST Month 7 |
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| ALT Day 56 |
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| ALT Month 7 |
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| Alkaline Phosphatase Day 56 |
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| Alkaline Phosphatase Month 7 |
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| Bilirubin Day 56 |
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| Bilirubin Month 7 |
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| Red Blood Cells Day 56 |
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| Red Blood Cells Month 7 |
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| Creatinine Day 56 |
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| Creatinine Month 7 |
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| Sodium Day 56 |
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| Sodium Month 7 |
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