Immunogenicity, Safety and Tolerability of a Neisseria Meningitidis Serogroup B Bivalent Recominant Lipoprotein 2086 Vaccine (Bivalent rLP2086) in Healthy Toddlers.

Local reactions included tenderness at injection site, swelling and redness collected by using an electronic diary (e-diary). Tenderness was graded as: mild (hurted if gently touched), moderate (hurted if gently touched with crying) and severe (caused limitation of limb movement). Redness and swelling were graded as: mild (0.5-2.0 centimeter \[cm\]), moderate (2.5 to 7.0 cm) and severe (\>7.0 cm).

Time frame: within 7 Days after Vaccination 1

Population: Safety population: all participants who received at least 1 dose of an investigational product (rLP2086 or HAV vaccine) and had safety data available.

Local reactions included tenderness at injection site, swelling and redness collected by using an e-diary. Tenderness was graded as: mild (hurted if gently touched), moderate (hurted if gently touched with crying) and severe (caused limitation of limb movement). Redness and swelling were graded as: mild (0.5-2.0 cm), moderate (2.5 to 7.0 cm) and severe (\>7.0 cm).

Time frame: within 7 Days after Vaccination 2

Population: Safety population: all participants who received at least 1 dose of an investigational product (rLP2086 or HAV vaccine) and had safety data available. Here, N signifies number of participants evaluable for this outcome measure.

Local reactions included tenderness at injection site, swelling and redness collected by using an e-diary. Tenderness was graded as: mild (hurted if gently touched), moderate (hurted if gently touched with crying) and severe (caused limitation of limb movement). Redness and swelling were graded as: mild (0.5-2.0 cm), moderate (2.5 to 7.0 cm) and severe (\>7.0 cm).

Time frame: within 7 Days after Vaccination 3

Population: Safety population: all participants who received at least 1 dose of an investigational product (rLP2086 or HAV vaccine) and had safety data available. Here, N signifies number of participants evaluable for this outcome measure.

Systemic reactions included fever, irritability, drowsiness, loss of or decreased appetite and were recorded by using an e-diary. Fever was graded as 38.0 to 38.4 degree Celsius (C), 38.5 to 38.9 degree C, 39.0 to 39.4 degree C, \>39.5 to 40.0 degree C and \>40.0 degree C. Irritability was graded as mild (easily consolable), moderate (requiring increased attention) and severe (inconsolable). Drowsiness was graded as mild (Increased or prolonged sleeping bouts), moderate (slightly subdued interfering with daily activity) and severe (disabling not interested in usual daily activity). Loss of or decreased appetite was graded as mild (decreased interest in eating), moderate (decreased oral intake) and severe (refusal to feed).

Time frame: within 7 Days after Vaccination 1

Population: Safety population: all participants who received at least 1 dose of an investigational product (rLP2086 or HAV vaccine) and had safety data available.

Systemic reactions included fever, irritability, drowsiness, loss of or decreased appetite and were recorded by using an e-diary. Fever was graded as 38.0 to 38.4 degree C, 38.5 to 38.9 degree C, 39.0 to 39.4 degree C, \>39.5 to 40.0 degree C and \>40.0 degree C. Irritability was graded as mild (easily consolable), moderate (requiring increased attention) and severe (inconsolable). Drowsiness was graded as mild (Increased or prolonged sleeping bouts), moderate (slightly subdued interfering with daily activity) and severe (disabling not interested in usual daily activity). Loss of or decreased appetite was graded as mild (decreased interest in eating), moderate (decreased oral intake) and severe (refusal to feed).

Time frame: within 7 Days after Vaccination 2

Population: Safety population: all participants who received at least 1 dose of an investigational product (rLP2086 or HAV vaccine) and had safety data available. Here, N signifies number of participants evaluable for this outcome measure.

Systemic reactions included fever, irritability, drowsiness, loss of or decreased appetite and were recorded by using an e-diary. Fever was graded as 38.0 to 38.4 degree C, 38.5 to 38.9 degree C, 39.0 to 39.4 degree C, \>39.5 to 40.0 degree C and \>40.0 degree C. Irritability was graded as mild (easily consolable), moderate (requiring increased attention) and severe (inconsolable). Drowsiness was graded as mild (Increased or prolonged sleeping bouts), moderate (slightly subdued interfering with daily activity) and severe (disabling not interested in usual daily activity). Loss of or decreased appetite was graded as mild (decreased interest in eating), moderate (decreased oral intake) and severe (refusal to feed).

Time frame: within 7 Days after Vaccination 3

Population: Safety population: all participants who received at least 1 dose of an investigational product (rLP2086 or HAV vaccine) and had safety data available. Here, N signifies number of participants evaluable for this outcome measure.

An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; lack of efficacy in an approved indication; important medical event. A MAE was defined as a non-serious AE that resulted in an evaluation at a medical facility. An NDCMC was defined as a disease or medical condition that was not identified prior to study start and was expected to be persistent or otherwise long-lasting in its effects.

Time frame: From the Vaccination 1 up to 1 month after Vaccination 3

Population: Safety population: all participants who received at least 1 dose of the investigational product (rLP2086 or HAV/saline) and had safety data available.

An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; lack of efficacy in an approved indication; important medical event. A MAE was defined as a non-serious AE that resulted in an evaluation at a medical facility. An NDCMC was defined as a disease or medical condition that was not identified prior to study start and was expected to be persistent or otherwise long-lasting in its effects.

Time frame: within 30 Days after any Vaccination

Population: Safety population: all participants who received at least 1 dose of the investigational product (rLP2086 or HAV/saline) and had safety data available.

An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; lack of efficacy in an approved indication; important medical event. A MAE was defined as a non-serious AE that resulted in an evaluation at a medical facility. An NDCMC was defined as a disease or medical condition that was not identified prior to study start and was expected to be persistent or otherwise long-lasting in its effects. Immediate AE was defined as AEs occurring within the first 30 minutes after investigational product administration.

Time frame: within 30 Days after Vaccination 1

Population: Safety population: all participants who received at least 1 dose of an investigational product (rLP2086 or HAV vaccine) and had safety data available.

An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; lack of efficacy in an approved indication; important medical event. A MAE was defined as a non-serious AE that resulted in an evaluation at a medical facility. An NDCMC was defined as a disease or medical condition that was not identified prior to study start and was expected to be persistent or otherwise long-lasting in its effects. Immediate AE was defined as AEs occurring within the first 30 minutes after investigational product administration.

Time frame: within 30 Days after Vaccination 2

Population: Safety population: all participants who received at least 1 dose of an investigational product (rLP2086 or HAV vaccine) and had safety data available. Here, N signifies number of participants evaluable for this outcome measure.

An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; lack of efficacy in an approved indication; important medical event. A MAE was defined as a non-serious AE that resulted in an evaluation at a medical facility. An NDCMC was defined as a disease or medical condition that was not identified prior to study start and was expected to be persistent or otherwise long-lasting in its effects. Immediate AE was defined as AEs occurring within the first 30 minutes after investigational product administration.

Time frame: within 30 Days after Vaccination 3

Population: Safety population: all participants who received at least 1 dose of an investigational product (rLP2086 or HAV vaccine) and had safety data available. Here, N signifies number of participants evaluable for this outcome measure.

An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; lack of efficacy in an approved indication; important medical event. A MAE was defined as a non-serious AE that resulted in an evaluation at a medical facility. An NDCMC was defined as a disease or medical condition that was not identified prior to study start and was expected to be persistent or otherwise long-lasting in its effects.

Time frame: From 1 month after Vaccination 3 up to 6 months after Vaccination 3

Population: Safety population: all participants who received at least 1 dose of the investigational product (rLP2086 or HAV/saline) and had safety data available. Here N signifies number of participants evaluable for this outcome measure.

An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; lack of efficacy in an approved indication; important medical event. A MAE was defined as a non-serious AE that resulted in an evaluation at a medical facility. An NDCMC was defined as a disease or medical condition that was not identified prior to study start and was expected to be persistent or otherwise long-lasting in its effects.

Time frame: From Vaccination 1 up to 6 months after Vaccination 3

Population: Safety population: all participants who received at least 1 dose of the investigational product (rLP2086 or HAV/saline) and had safety data available.

Percentage of participants achieving hSBA titer \>= LLOQ were computed along with corresponding 2-sided 95 percent (%) confidence interval (CIs). LLOQ was 1:16 for PMB80 (A22) and 1:8 for PMB2001 (A56), PMB2948 (B24) and PMB2707 (B44).

Time frame: 1 month after Vaccination 3

Population: All eligible participants randomized to study received,scheduled investigational products, had pre and post vaccination blood drawn with valid and determinate assay results and had no important protocol deviation. Here,overall number of participants analyzed (N) signifies number of participants evaluable for this outcome measure.

Local reactions included pain at injection site, swelling and redness collected by using an e-diary. Pain at injection site was graded as: mild (does not interfere with activity), moderate (interferes with activity) and severe (prevents daily activity). A caliper was used to measure the redness or swelling area. Caliper units were converted to centimeters (cm) according to 1 caliper unit = 0.5 cm. Redness and swelling were graded as: none (0 cm) mild (0.5-2.0 cm), moderate (\>=2.0 to 7.0 cm) and severe (\>7.0 cm).

Time frame: Within 7 days after booster vaccination

Population: Booster safety population included all participants who received the booster dose at 23 months after vaccination 3 (Visit 12), and for whom safety information was available.

Systemic reactions included fever, vomiting, diarrhea, headache, fatigue, muscle pain and joint pain were recorded by using an e-diary. Fever was defined as a temperature of greater than or equal to (\>=) 38.0 degree Celsius and was graded as 38.0 degree Celsius (C) to 38.4 degree C, 38.5 degree C to 38.9 degree C, 39.0 degree C to 39.4 degree C, 39.5 degree C to 40.0 degree C, \>40.0 degree C. Vomiting was graded as mild (1 to 2 times in 24 hours), moderate (\>2 times in 24 hours) and severe (requires IV hydration). Diarrhea was graded as mild (2 to 3 loose stools in 24 hours), moderate (4 to 5 loose stools in 24 hours), and severe (6 or more loose stools in 24 hours). Fatigue, headache, muscle pain and joint pain were graded as: mild (did not interfere with activity), moderate (some interference with activity) and severe (prevented daily routine activity). The use and type of antipyretic medication was also recorded in the e-diary daily.

Time frame: Within 7 days after booster vaccination

Population: Booster safety population included all participants who received the booster dose at 23 months after Vaccination 3 (Visit 12), and for whom safety information was available.

An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship.

Time frame: Booster vaccination up to 1 month after booster vaccination

Population: Booster safety population included all participants who received the booster dose at 23 months after Vaccination 3 (Visit 12), and for whom safety information was available.

Percentage of participants achieving hSBA titer \>= LLOQ were computed along with corresponding 2-sided 95% CIs. LLOQ was 1:16 for PMB80 (A22) and 1:8 for PMB2001 (A56), PMB2948 (B24), and PMB2707 (B44).

Time frame: 1, 6, 12, 24 months after Vaccination 3

Population: Evaluable immunogenicity population: all eligible participants randomized to study, received scheduled investigational products, had pre and post vaccination blood drawn with valid and determinate assay results and had no important protocol deviation. Here N signifies number of participants evaluable for this outcome measure and number analyzed (n) signifies participants evaluable at specific rows.

Percentage of participants achieving hSBA titer \>= LLOQ were computed along with corresponding 2-sided 95 % CIs. The LLOQ was 1:16 for A22 and 1:8 for A56, B24, and B44.

Time frame: Before booster vaccination and 1 month after booster vaccination

Population: Booster evaluable immunogenicity population: participants eligible for study, randomized to 120 mcg bivalent rLP2086 during stage 1, received scheduled investigational products, had blood drawn prior to booster vaccination dose and post-booster vaccination blood drawn (Visit 13) within 28-42 days from booster vaccination (Visit 12) and had no important protocol deviation. N=number of participants evaluable for this outcome measure and number analyzed=participants evaluable at specific rows.

Percentage of participants achieving hSBA titer \>= LLOQ were computed along with corresponding 2-sided 95% CIs. LLOQ was 1:16 for PMB80 (A22) and 1:8 for PMB2001 (A56), PMB2948 (B24), and PMB2707 (B44).

Time frame: 1 month (Mon) after Vaccination (Vac) 2

Population: Evaluable immunogenicity population: all eligible participants randomized to study, received scheduled investigational products, had pre and post vaccination blood drawn with valid and determinate assay results and had no important protocol deviation. Here N signifies number of participants evaluable for this outcome measure.

Immediate AE was defined as AEs occurring within the first 30 minutes after investigational product administration.

Time frame: Within 30 minutes after booster vaccination

Population: Booster safety population included all participants who received the booster dose at 23 months after vaccination 3 (Visit 12), and for whom safety information was available.

SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; lack of efficacy in an approved indication; important medical event. A MAE was defined as a non-serious AE that resulted in an evaluation at a medical facility. An NDCMC was defined as a disease or medical condition that was not identified prior to study start and was expected to be persistent or otherwise long-lasting in its effects.

Time frame: Booster vaccination to 1 month after booster vaccination (T1), 1 month after booster vaccination to 6 months after booster vaccination (T2) and booster vaccination through 6 months after booster vaccination (T3)

Population: Booster safety population included all participants who received the booster dose at 23 months after Vaccination 3 (Visit 12), and for whom safety information was available.

Time frame: Before Vaccination 1 (T1), 1 month after Vaccination 2 (T2), 1 month after Vaccination 3 (T3), 6 months after Vaccination 3 (T4), 12 months after Vaccination 3 (T5) and 24 months after Vaccination 3 (T6)

Population: Evaluable immunogenicity population: all eligible participants randomized to study, received scheduled investigational products, had pre and post vaccination blood drawn with valid and determinate assay results and had no important protocol deviation. Here N signifies number of participants evaluable for this outcome measure and n signifies participants evaluable at specific rows.