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| Name | Class |
|---|---|
| Department of Health and Human Services | FED |
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Evaluate Safety, Tolerability and Immune Response of Adjuvanted H5N1 Cell Culture Derived Influenza Vaccine in Adult Subjects.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| aH5N1c-High Dose | Experimental | Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart. |
|
| aH5N1c-Low dose | Experimental | Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Adjuvanted H5N1 pandemic influenza vaccine | Biological | Comparison of two doses of aH5N1c vaccine |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentages Of Subjects Achieving Hemagglutinin Inhibition (HI) Titers ≥40 Against A/H5N1 Strain. | The optimal aH5N1c vaccine formulation was evaluated in terms of percentages of subjects achieving HI titers ≥40 against homologous A/H5N1 strain, three weeks after second vaccination with either low dose or high dose of aH5N1c vaccine, according to the Center for Biologics Evaluation and Research (CBER) criterion. CBER criterion for the adult population is met if the lower limit of the two-sided 95% confidence interval (CI) for the percentages of subjects achieving HI titer ≥40 meets or exceeds 70%. | Three weeks after 2nd vaccination (day 43) |
| Percentages Of Subjects Achieving Seroconversion Against A/H5N1 Strain. | Immunogenicity was measured in terms of the percentages of subjects achieving seroconversion or significant increase in HI titer against the vaccine strain, three weeks after receiving two injections of low dose or high dose of aH5N1c vaccine according to the CBER criterion. Seroconversion is defined as either a) in subjects with a prevaccination HI titer <10, a postvaccination titer ≥40; or b) in subjects with prevaccination HI titer ≥10, a minimum four-fold rise in postvaccination HI antibody titer. CBER criterion for the adult population is met if the lower limit of the two-sided 95% CI for the percentages of subjects achieving seroconversion for HI antibody titer meets or exceeds 40%. | Three weeks after 2nd vaccination (day 43) |
| Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AE), After Any Vaccination. | Safety was assessed using the number of subjects who reported solicited local and systemic AEs following vaccination with either low or high dose of aH5N1c vaccine. | From day 1 through day 7 after any vaccination. |
| Number of Subjects Reporting Unsolicited AEs After Any Vaccination. | Safety was assessed using the number of subjects who reported any unsolicited adverse events, adverse events possibly or probably related to study vaccine, serious adverse events (SAEs), new onset of chronic diseases (NOCDs), medically attended AEs, AEs of special interest (AESIs), AEs leading to withdrawal from study following vaccination with either low or high dose of aH5N1c vaccine. |
| Measure | Description | Time Frame |
|---|---|---|
| Geometric Mean Ratios Against A/H5N1 Strain Following 2-dose Vaccination Schedule of Either Low Dose or High Dose aH5N1c Vaccine. | Immunogenicity was measured as the geometric mean ratio (GMR). The ratio of postvaccination to prevaccination HI GMTs, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose of aH5N1c is reported. The criterion is met according to the European Committee for Medicinal Products for Human Use (CHMP) criterion if the geometric mean increase GMR (day 43/day 1) in HI antibody titer is >2.5 for subjects 18-60 years of age. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Vaccines and Diagnostics | Novartis Vaccines | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 1 Miami Research Associates | Miami | Florida | 33143 | United States | ||
| 2 Mercy Health Research |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30968056 | Derived | Frey SE, Shakib S, Chanthavanich P, Richmond P, Smith T, Tantawichien T, Kittel C, Jaehnig P, Mojares Z, Verma B, Kanesa-Thasan N, Hohenboken M. Safety and Immunogenicity of MF59-Adjuvanted Cell Culture-Derived A/H5N1 Subunit Influenza Virus Vaccine: Dose-Finding Clinical Trials in Adults and the Elderly. Open Forum Infect Dis. 2019 Mar 1;6(4):ofz107. doi: 10.1093/ofid/ofz107. eCollection 2019 Apr. |
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All enrolled subjects were included in the trial.
Subjects were enrolled at 4 centers in the US, 3 centers in Australia and 1 center in Thailand.
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| ID | Title | Description |
|---|---|---|
| FG000 | High Dose | Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart. |
| FG001 | Low Dose | Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | High Dose | Subjects received 2 injections of a high dose MF59 adjuvanted cell-culture derived monovalent H5N1 vaccine three weeks apart. |
| BG001 | Low Dose | Subjects received 2 injections of a low dose MF59 adjuvanted cell-culture derived monovalent H5N1 vaccine three weeks apart. |
| 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 | Percentages Of Subjects Achieving Hemagglutinin Inhibition (HI) Titers ≥40 Against A/H5N1 Strain. | The optimal aH5N1c vaccine formulation was evaluated in terms of percentages of subjects achieving HI titers ≥40 against homologous A/H5N1 strain, three weeks after second vaccination with either low dose or high dose of aH5N1c vaccine, according to the Center for Biologics Evaluation and Research (CBER) criterion. CBER criterion for the adult population is met if the lower limit of the two-sided 95% confidence interval (CI) for the percentages of subjects achieving HI titer ≥40 meets or exceeds 70%. | Analysis was done on the Full Analysis Set (FAS) i.e., the subjects who actually receive at least one dose of study vaccination and provide at least one evaluable serum sample both before (baseline) and after vaccination. | Posted | Number | 95% Confidence Interval | Percentages of subjects | Three weeks after 2nd vaccination (day 43) |
|
Solicited local and systemic adverse events from day 1 to 7. SAEs and Unsolicited AEs (other than SAEs) from day 1 to 387.
All Solicited AEs are classified as systematic assessment and all unsolicited AEs are classified as non-systematic assessment.
Subjects who did not provide unsolicited safety data were excluded from safety evaluation.
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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 | High Dose | Subjects received 2 injections of a high dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| MYOCARDIAL INFARCTION | Cardiac disorders | MedDRA 17.0 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| NAUSEA | Gastrointestinal disorders | MedDRA 17.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Posting Director | Novartis Vaccines and Diagnostics | RegistryContactVaccinesUS@novartis.com |
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| ID | Term |
|---|---|
| D007251 | Influenza, Human |
| D005585 | Influenza in Birds |
| ID | Term |
|---|---|
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D009976 | Orthomyxoviridae Infections |
| D012327 | RNA Virus Infections |
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| Any unsolicited AEs - day 1 through day 22 after any vaccination. SAEs, NOCDs. medically attended AEs, AESIs, AEs leading to study withdrawal- day 1 to day 387 |
| Day 1; day 22; day 43 and day 387 |
| Percentages Of Subjects With HI Titers ≥40 Against A/H5N1 Strain. | Immunogenicity was assessed in terms of percentage of subjects achieving HI titers ≥40, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose of aH5N1c according to the CHMP criterion. European Licensure (CHMP) criterion is met if the percentage of subjects achieving (at day 43) HI titers ≥40 is >70%. | Day 1, day 22, day 43 and day 387 |
| Percentages Of Subjects Achieving Seroconversion Against A/H5N1 Strain. | Immunogenicity was assessed in terms of percentages of subjects achieving seroconversion in HI titers, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose aH5N1c vaccine according to the CHMP criterion. Seroconversion is defined as: a) for subjects with a prevaccination HI titer <10, a postvaccination titer ≥40; or b) for subjects with prevaccination HI titer ≥10, a minimum four-fold rise in postvaccination HI antibody titer. The criterion is met according to the European (CHMP) guideline if the percentage of subjects achieving seroconversion (at day 43) is >40%. | Day 22, day 43 and day 387 |
| St Louis |
| Missouri |
| 63141 |
| United States |
| 3 Saint Louis University | St Louis | Missouri | 63141 | United States |
| 4 Benchmark Medical Research | Austin | Texas | 78705 | United States |
| 48 Hunter Clinical Research | Newcastle | New South Wales | 2292 | Australia |
| 46 CMAX | Adelaide | South Australia | 5000 | Australia |
| 47 Linear Clinical Research | Nedlands | Western Australia | 6009 | Australia |
| 80 Faculty of Tropical Medicine | Bangkok | 1040 | Thailand |
| Lost to Follow-up |
|
| Unclassified |
|
| Protocol Violation |
|
| Withdrawal by Subject |
|
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
Subjects received 2 injections of a high dose MF59 adjuvanted cell-culture derived monovalent H5N1 vaccine three weeks apart. |
| OG001 | Low Dose | Subjects received 2 injections of a low dose MF59 adjuvanted cell-culture derived monovalent H5N1 vaccine three weeks apart. |
|
|
| Primary | Percentages Of Subjects Achieving Seroconversion Against A/H5N1 Strain. | Immunogenicity was measured in terms of the percentages of subjects achieving seroconversion or significant increase in HI titer against the vaccine strain, three weeks after receiving two injections of low dose or high dose of aH5N1c vaccine according to the CBER criterion. Seroconversion is defined as either a) in subjects with a prevaccination HI titer <10, a postvaccination titer ≥40; or b) in subjects with prevaccination HI titer ≥10, a minimum four-fold rise in postvaccination HI antibody titer. CBER criterion for the adult population is met if the lower limit of the two-sided 95% CI for the percentages of subjects achieving seroconversion for HI antibody titer meets or exceeds 40%. | This analysis was done on the FAS population. | Posted | Number | 95% Confidence Interval | Percentages of subjects | Three weeks after 2nd vaccination (day 43) |
|
|
|
| Primary | Number of Subjects Reporting Solicited Local and Systemic Adverse Events (AE), After Any Vaccination. | Safety was assessed using the number of subjects who reported solicited local and systemic AEs following vaccination with either low or high dose of aH5N1c vaccine. | Analysis was done on the safety dataset, i.e. the subjects in the exposed population who provided postvaccination safety data. | Posted | Number | Number of subjects | From day 1 through day 7 after any vaccination. |
|
|
|
| Primary | Number of Subjects Reporting Unsolicited AEs After Any Vaccination. | Safety was assessed using the number of subjects who reported any unsolicited adverse events, adverse events possibly or probably related to study vaccine, serious adverse events (SAEs), new onset of chronic diseases (NOCDs), medically attended AEs, AEs of special interest (AESIs), AEs leading to withdrawal from study following vaccination with either low or high dose of aH5N1c vaccine. | Analysis was done on the safety dataset, i.e. the subjects in the exposed population who provided postvaccination safety data. | Posted | Number | Number of subjects | Any unsolicited AEs - day 1 through day 22 after any vaccination. SAEs, NOCDs. medically attended AEs, AESIs, AEs leading to study withdrawal- day 1 to day 387 |
|
|
|
| Secondary | Geometric Mean Ratios Against A/H5N1 Strain Following 2-dose Vaccination Schedule of Either Low Dose or High Dose aH5N1c Vaccine. | Immunogenicity was measured as the geometric mean ratio (GMR). The ratio of postvaccination to prevaccination HI GMTs, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose of aH5N1c is reported. The criterion is met according to the European Committee for Medicinal Products for Human Use (CHMP) criterion if the geometric mean increase GMR (day 43/day 1) in HI antibody titer is >2.5 for subjects 18-60 years of age. | Analysis was done on the FAS set. | Posted | Geometric Mean | 95% Confidence Interval | Ratio | Day 1; day 22; day 43 and day 387 |
|
|
|
| Secondary | Percentages Of Subjects With HI Titers ≥40 Against A/H5N1 Strain. | Immunogenicity was assessed in terms of percentage of subjects achieving HI titers ≥40, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose of aH5N1c according to the CHMP criterion. European Licensure (CHMP) criterion is met if the percentage of subjects achieving (at day 43) HI titers ≥40 is >70%. | Analysis was done on the FAS set. | Posted | Number | 95% Confidence Interval | Percentages of subjects | Day 1, day 22, day 43 and day 387 |
|
|
|
| Secondary | Percentages Of Subjects Achieving Seroconversion Against A/H5N1 Strain. | Immunogenicity was assessed in terms of percentages of subjects achieving seroconversion in HI titers, 3 weeks after first vaccination, 3 weeks after second vaccination and 12 months after second vaccination of either low dose or high dose aH5N1c vaccine according to the CHMP criterion. Seroconversion is defined as: a) for subjects with a prevaccination HI titer <10, a postvaccination titer ≥40; or b) for subjects with prevaccination HI titer ≥10, a minimum four-fold rise in postvaccination HI antibody titer. The criterion is met according to the European (CHMP) guideline if the percentage of subjects achieving seroconversion (at day 43) is >40%. | Analysis was done on the FAS set. | Posted | Number | 95% Confidence Interval | Percentages of subjects | Day 22, day 43 and day 387 |
|
|
|
| 20 |
| 485 |
| 371 |
| 485 |
| EG001 | Low Dose | Subjects received 2 injections of a low dose of cell culture-derived adjuvanted monovalent inactivated subunit H5N1 vaccine three weeks apart. | 8 | 490 | 324 | 490 |
| EG002 | Total | Total of high dose and low dose groups. | 28 | 975 | 695 | 975 |
| PANCREATITIS | Gastrointestinal disorders | MedDRA 17.0 | Non-systematic Assessment |
|
| NON-CARDIAC CHEST PAIN | General disorders | MedDRA 17.0 | Non-systematic Assessment |
|
| CHOLECYSTITIS | Hepatobiliary disorders | MedDRA 17.0 | Non-systematic Assessment |
|
| CHOLELITHIASIS | Hepatobiliary disorders | MedDRA 17.0 | Non-systematic Assessment |
|
| JAUNDICE | Hepatobiliary disorders | MedDRA 17.0 | Non-systematic Assessment |
|
| APPENDICITIS | Infections and infestations | MedDRA 17.0 | Non-systematic Assessment |
|
| GASTROENTERITIS VIRAL | Infections and infestations | MedDRA 17.0 | Non-systematic Assessment |
|
| INFLUENZA | Infections and infestations | MedDRA 17.0 | Non-systematic Assessment |
|
| PNEUMONIA | Infections and infestations | MedDRA 17.0 | Non-systematic Assessment |
|
| PYELONEPHRITIS | Infections and infestations | MedDRA 17.0 | Non-systematic Assessment |
|
| SEPSIS | Infections and infestations | MedDRA 17.0 | Non-systematic Assessment |
|
| BRAIN CONTUSION | Injury, poisoning and procedural complications | MedDRA 17.0 | Non-systematic Assessment |
|
| CONTUSION | Injury, poisoning and procedural complications | MedDRA 17.0 | Non-systematic Assessment |
|
| LIMB CRUSHING INJURY | Injury, poisoning and procedural complications | MedDRA 17.0 | Non-systematic Assessment |
|
| POST LAMINECTOMY SYNDROME | Injury, poisoning and procedural complications | MedDRA 17.0 | Non-systematic Assessment |
|
| POSTOPERATIVE ADHESION | Injury, poisoning and procedural complications | MedDRA 17.0 | Non-systematic Assessment |
|
| ROAD TRAFFIC ACCIDENT | Injury, poisoning and procedural complications | MedDRA 17.0 | Non-systematic Assessment |
|
| LARYNGEAL SQUAMOUS CELL CARCINOMA | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 17.0 | Non-systematic Assessment |
|
| CEREBRAL HAEMORRHAGE | Nervous system disorders | MedDRA 17.0 | Non-systematic Assessment |
|
| NERVE COMPRESSION | Nervous system disorders | MedDRA 17.0 | Non-systematic Assessment |
|
| SUBARACHNOID HAEMORRHAGE | Nervous system disorders | MedDRA 17.0 | Non-systematic Assessment |
|
| ABORTION MISSED | Pregnancy, puerperium and perinatal conditions | MedDRA 17.0 | Non-systematic Assessment |
|
| ABORTION SPONTANEOUS | Pregnancy, puerperium and perinatal conditions | MedDRA 17.0 | Non-systematic Assessment |
|
| NEPHROLITHIASIS | Renal and urinary disorders | MedDRA 17.0 | Non-systematic Assessment |
|
| ACUTE RESPIRATORY FAILURE | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Non-systematic Assessment |
|
| RAYNAUD'S PHENOMENON | Vascular disorders | MedDRA 17.0 | Non-systematic Assessment |
|
| FATIGUE | General disorders | MedDRA 17.0 | Systematic Assessment |
|
| INJECTION SITE ERYTHEMA | General disorders | MedDRA 17.0 | Systematic Assessment |
|
| INJECTION SITE HAEMORRHAGE | General disorders | MedDRA 17.0 | Systematic Assessment |
|
| INJECTION SITE INDURATION | General disorders | MedDRA 17.0 | Systematic Assessment |
|
| INJECTION SITE PAIN | General disorders | MedDRA 17.0 | Systematic Assessment |
|
| MALAISE | General disorders | MedDRA 17.0 | Systematic Assessment |
|
| UPPER RESPIRATORY TRACT INFECTION | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
|
| DECREASED APPETITE | Metabolism and nutrition disorders | MedDRA 17.0 | Systematic Assessment |
|
| ARTHRALGIA | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Systematic Assessment |
|
| MYALGIA | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Systematic Assessment |
|
| HEADACHE | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
|
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| D014777 | Virus Diseases |
| D012140 | Respiratory Tract Diseases |
| D001715 | Bird Diseases |
| D000820 | Animal Diseases |
| Injection site Induration(N=471,471) |
|
| Injection site Ecchymosis(N=472,471) |
|
| Injection site Pain(N=471,470) |
|
| Any Systemic |
|
| Nausea(N=472,471) |
|
| Myalgia(N=472,469) |
|
| Arthralgia(N=471,467) |
|
| Headache(N=471,469) |
|
| Fatigue(N=471,469) |
|
| Loss of Appetite(N=472,469) |
|
| Malaise(N=472,467) |
|
| Fever (≥38°C)(N=472,469) |
|
| Treatment of pain and (or) fever(N=471,470) |
|
| Prevention of pain and (or) fever(N=471,470) |
|
| Fever (≥40°C)(N=472,469) |
|
| Any SAEs |
|
| Deaths |
|
| Medically attended AEs |
|
| AEs resulting in premature withdrawal from study |
|
| AEs of Special Interest |
|
| AEs leading to New Onset of Chronic Disease |
|
| Day387/Day1 (N=411,395) |
|
| Day 43 (N=451,440) |
|
| Day 387 (N=411,395) |
|
| Day 387 (N=411,395) |
|