Influenza HA Ferritin Vaccine, Alone or in Prime-Boost Regimens With an Influenza DNA Vaccine in Healthy Adults

Subjects recorded the occurrence of solicited symptoms on a diary card for 7 days after the DNA A/Sing study product administration and reviewed the diary card with clinic staff at a follow up visit. Subjects were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than one time at any severity during the reporting period. The number reported for Any Local Symptom is the number of subjects reporting any local symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (FDA Guidance - September 2007).

Time frame: 7 days after DNA A/Sing product administration, at approximately Week 1

Population: Population included all enrolled subjects who received the DNA A/Sing study injection and provided safety data (via diary card and/or laboratory results) following the injection (N=20).

Subjects recorded the occurrence of solicited symptoms on a diary card for 7 days after each HA-F A/Sing study product administration and reviewed the diary card with clinic staff at a follow up visit. Subjects were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than one time at any severity during the reporting period. The number reported for Any Local Symptom is the number of subjects reporting any local symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (FDA Guidance - September 2007).

Time frame: 7 days after each HA-F A/Sing product administration, at approximately Week 1 and/or at approximately Week 17

Population: Population included all enrolled subjects who received at least one HA-F A/Sing study injection and provided safety data (via diary card and/or laboratory results) following the injection (N=47). Two subjects in Group 3A and one subject in Group 3B received the prime DNA A/Sing injection but did not receive the boost HA-F A/Sing injection.

Subjects recorded the occurrence of solicited symptoms on a diary card for 7 days after DNA A/Sing study product administration and reviewed the diary card with clinic staff at a follow up visit. Subjects were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than one time at any severity during the reporting period. The number reported for Any Systemic Symptom is the number of subjects reporting any systemic symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (FDA Guidance - September 2007).

Time frame: 7 days after DNA A/Sing product administration, at approximately Week 1

Population: Population included all enrolled subjects who received the DNA A/Sing study injection and provided safety data (via diary card and/or laboratory results) following the injection (N=20).

Subjects recorded the occurrence of solicited symptoms on a diary card for 7 days after each HA-F A/Sing study product administration and reviewed the diary card with clinic staff at a follow up visit. Subjects were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than one time at any severity during the reporting period. The number reported for Any Systemic Symptom is the number of subjects reporting any systemic symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (FDA Guidance - September 2007).

Time frame: 7 days after each HA-F A/Sing product administration, at approximately Week 1 and/or at approximately Week 17

Population: Population included all enrolled subjects who received at least one HA-F A/Sing study injection and provided safety data (via diary card and/or laboratory results) following the injection (N=47). Two subjects in Group 3A and one subject in Group 3B received the prime DNA A/Sing injection but did not receive the boost HA-F A/Sing injection.

Any abnormal laboratory results recorded as unsolicited adverse events (AEs) are summarized. Safety laboratory parameters included hematology (hemoglobin, hematocrit, platelets, and white blood cell (WBC), red blood cell (RBC), neutrophil, lymphocyte, monocyte, eosinophil and basophil percents/counts) and chemistry (alanine aminotransferase (ALT), alanine aspartate (AST), alkaline phosphate (ALP), creatinine and total bilirubin). Complete blood count (CBC) with differential, total bilirubin, AST, ALT, and ALP results were collected at screening (≤ 84 days before enrollment), Day 0 prior to study product administration (baseline), and at Days 14, 28, 112, 140 and 280. Creatinine results were collected at screening, Day 0 and Day 6. Institutional laboratory normal ranges as well as the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials FDA Guidance, September 2007 were used.

Time frame: Day 0 through Day 280

Population: Population included all enrolled subjects who had laboratory results available at any study visit post baseline.

Influenza or influenza-like illness (ILI) were recorded in the study database from receipt of the first study product administration through the last study visit.

Time frame: Day 0 through Day 280

Population: Population included all enrolled subjects who received the DNA A/Sing study injection (N=20).

Influenza or influenza-like illness (ILI) were recorded in the study database from receipt of the first study product administration through the last study visit.

Time frame: Day 0 through Day 280

Population: Population included all enrolled subjects who received at least one HA-F A/Sing study injection (N=47). Two subjects in Group 3A and one subject in Group 3B received the prime DNA A/Sing injection but did not receive the boost HA-F A/Sing injection.

Unsolicited AEs and attribution assessments were recorded in the study database from receipt of the first study product administration through the visit scheduled for 4 weeks after each study product administration. At other time periods between study product administrations and when greater than 4 weeks after the last study product administration, only serious AEs (SAEs reported as a separate outcome and in the AE module), influenza-like illness (ILI) or influenza (reported as a separate outcome) and new chronic medical conditions that required ongoing medical management were recorded through the last study visit. The relationship between an AE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A subject with multiple experiences of the same event is counted once using the event of worst severity.

Time frame: Day 0 through 4 weeks after DNA A/Sing product administration, up to Week 4

Population: Population included all enrolled subjects who received the DNA A/Sing study injection and provided safety data (via diary card and/or laboratory results) following the injection (N=20).

Unsolicited AEs and attribution assessments were recorded in the study database from receipt of the first study product administration through the visit scheduled for 4 weeks after each study product administration. At other time periods between study product administrations and when greater than 4 weeks after the last study product administration, only serious AEs (SAEs reported as a separate outcome and in the AE module), influenza-like illness (ILI) or influenza (reported as a separate outcome) and new chronic medical conditions that required ongoing medical management were recorded through the last study visit. The relationship between an AE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A subject with multiple experiences of the same event is counted once using the event of worst severity.

Time frame: Day 0 through 4 weeks after each HA-F A/Sing product administration, up to Week 20

Population: Population included all enrolled subjects who received at least one HA-F A/Sing study injection and provided safety data (via diary card and/or laboratory results) following the injection (N=47). Two subjects in Group 3A and one subject in Group 3B received the prime DNA A/Sing injection but did not receive the boost HA-F A/Sing injection.

SAEs were recorded from receipt of first study product administration through the last expected study visit at Day 280. The relationship between a SAE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A subject with multiple experiences of the same event is counted once using the event of worst severity.

Time frame: Day 0 through Day 280

Population: Population included all enrolled subjects who received the DNA A/Sing study injection (N=20).

SAEs were recorded from receipt of first study product administration through the last expected study visit at Day 280. The relationship between a SAE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A subject with multiple experiences of the same event is counted once using the event of worst severity.

Time frame: Day 0 through Day 280

Population: Population included all enrolled subjects who received at least one HA-F A/Sing study injection (N=47). Two subjects in Group 3A and one subject in Group 3B received the prime DNA A/Sing injection but did not receive the boost HA-F A/Sing injection.

Hemagglutination inhibition assays (HAI) titers were determined against the homologous H2N2 A/Singapore/1/57 virus, and were summarized using geometric mean titers (GMTs). Negative samples were reported and GMTs were calculated using half the limit of detection. H2-naïve (ages 18-47 years) and H2-exposed (ages 52-70 years) subjects received either a single dose of 20 mcg HA-F A/Sing (H2-naïve), two doses of 60 mcg HA-F A/Sing 16 weeks apart (H2-naïve and H2-exposed), or a 4 mg DNA A/Sing prime followed by a single 60 mcg HA-F A/Sing boost at 16 weeks (H2-naïve and H2-exposed).

Time frame: Four weeks after the first dose for groups that received a single vaccination, at Week 4 or two weeks after the second dose for groups that received two vaccinations, at Week 18

Population: Overall number analyzed includes the H2-naïve adults (adults with no pre-existing immunity to H2) and H2-exposed adults (may have some H2 immunity). The H2-naïve and H2-exposed number analyzed rows reflect the number of subjects analyzed in each group.

Pseudoviral neutralization antibody titers were determined against the homologous H2N2 A/Singapore/1/57 virus, and were summarized using geometric mean 50% inhibitory concentration (IC50). Negative samples were reported and IC50 titers were calculated using half the limit of detection. H2-naïve (ages 18-47 years) and H2-exposed (ages 52-70 years) subjects received either a single dose of 20 mcg HA-F A/Sing (H2-naïve), two doses of 60 mcg HA-F A/Sing 16 weeks apart (H2-naïve and H2-exposed), or a 4 mg DNA A/Sing prime followed by a single 60 mcg HA-F A/Sing boost at 16 weeks (H2-naïve and H2-exposed).

Time frame: Four weeks after the first dose for groups that received a single vaccination, at Week 4 or two weeks after the second dose for groups that received two vaccinations, at Week 18

Population: Overall number analyzed includes the H2-naïve adults (adults with no pre-existing immunity to H2) and H2-exposed adults (may have some H2 immunity). The H2-naïve and H2-exposed number analyzed rows reflect the number of subjects analyzed in each group.

Seroconversion rate: the proportion of subjects achieving seroconversion in hemagglutination inhibition assay (HAI) antibody titer. Seroconversion rates for HAI were summarized as the proportion of individuals in each group experiencing a positive response, defined per the FDA criteria of positivity as either a baseline titer of less than 1:10 and a post vaccination titer of 1:40 or more or a baseline titer of 1:10 or more and a minimum four-fold rise after vaccination. H2-naïve (ages 18-47 years) and H2-exposed (ages 52-70 years) subjects received either a single dose of 20 mcg HA-F A/Sing (H2-naïve), two doses of 60 mcg HA-F A/Sing 16 weeks apart (H2-naïve and H2-exposed), or a 4 mg DNA A/Sing prime followed by a single 60 mcg HA-F A/Sing boost at 16 weeks (H2-naïve and H2-exposed).

Time frame: Four weeks after the first dose for groups that received a single vaccination, at Week 4 or two weeks after the second dose for groups that received two vaccinations, at Week 18

Population: Overall number analyzed includes the H2-naïve adults (adults with no pre-existing immunity to H2) and H2-exposed adults (may have some H2 immunity). The H2-naïve and H2-exposed number analyzed rows reflect the number of subjects analyzed in each group.