Immunogenicity, Safety and Tolerability of a Neisseria Meningitidis Serogroup B Bivalent Recominant Lipoprotein 2086 Vaccine (Bivalent rLP2086) in Healthy Toddlers.
- Conditions
- Meningococcal B Disease
- Interventions
- Biological: rLP2086 vaccineBiological: Pediatric HAV vaccine
- Registration Number
- NCT02534935
- Lead Sponsor
- Pfizer
- Brief Summary
The purpose of this study is to investigate the immunogenicity, safety and tolerability of a new vaccine that might prevent meningococcal B disease. The study will be conducted in healthy toddlers aged between 12 and 24 months.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 396
- Male or female subject aged 12 to <15 months or 18 to <24 months during sentinel-cohort enrollment, Or,12 to <24 months during expanded-cohort enrollment.
- Subjects must have received all vaccinations in the relevant National Immunization Program (NIP) for their age group.
- Subject is determined to be in good health by medical history, physical examination, and judgment of the investigator.
- Previous vaccination with any meningococcal serogroup B vaccine.
- Previous vaccination with HAV vaccine, or requirement to receive nonstudy HAV vaccine during Stage 1 of the study.
- Contraindication to vaccination with any HAV vaccine or known latex allergy.
- A previous anaphylactic reaction to any vaccine or vaccine-related component.
- Bleeding diathesis or condition associated with prolonged bleeding time that would contraindicate intramuscular injection.
- A known or suspected disorder of the immune system that would prevent an immune response to the vaccine, such as subjects with congenital or acquired defects in B-cell function or those receiving systemic immunosuppressive therapy. Subjects with terminal complement deficiency may be included.
- History of microbiologically proven disease caused by N meningitidis or Neisseria gonorrhoeae.
- Significant neurologic disorder or history of seizure (excluding simple febrile seizure).
- Receipt of any blood products, including immunoglobulin, within 6 months before the first study vaccination until the end of Stage 1.
- Current chronic use of systemic antibiotics.
- Received any investigational drugs, vaccines or devices within 28 days before administration of the first study vaccination and/or during study participation.
- Any neuroinflammatory or autoimmune condition, including but not limited to transverse myelitis, uveitis, optic neuritis, and multiple sclerosis.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description rLP2086 vaccine rLP2086 vaccine Arm stratified by age: ≥12 to \<18 months and ≥18 to \<24 months Control Pediatric HAV vaccine Arm stratified by age: ≥12 to \<18 months and ≥18 to \<24 months
- Primary Outcome Measures
Name Time Method Percentage of Participants Reporting Pre-specified Local Reactions Within 7 Days After Vaccination 3 within 7 Days after Vaccination 3 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).
Percentage of Participants Reporting Pre-specified Local Reactions Within 7 Days After Vaccination 2 within 7 Days after Vaccination 2 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).
Percentage of Participants With at Least 1 Adverse Event (AE), Serious Adverse Event (SAE), Medically Attended Adverse Event (MAE), Newly Diagnosed Chronic Medical Condition (NDCMC) and Immediate Adverse Event (IAE) Within 30 Days After Vaccination 1 within 30 Days after Vaccination 1 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.
Percentage of Participants With at Least 1 Serious Adverse Event (SAE), Medically Attended Adverse Event (MAE) and Newly Diagnosed Chronic Medical Condition (NDCMC) During the Follow up Phase From 1 month after Vaccination 3 up to 6 months after Vaccination 3 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.
Percentage of Participants With Serum Bactericidal Assay Using Human Complement (hSBA) Titers >= Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Neisseria Meningitidis Serogroup B (MnB) Test Strains 1 Month After Vaccination 3 1 month after Vaccination 3 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).
Percentage of Participants Reporting Pre-specified Local Reactions Within 7 Days After Vaccination 1 within 7 Days after Vaccination 1 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).
Percentage of Participants Reporting Systemic Events and Antipyretic Use Within 7 Days After Vaccination 1 within 7 Days after Vaccination 1 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).
Percentage of Participants With at Least 1 Adverse Event (AE), Serious Adverse Event (SAE), Medically Attended Adverse Event (MAE), Newly Diagnosed Chronic Medical Condition (NDCMC) and Immediate Adverse Event (IAE) Within 30 Days After Vaccination 2 within 30 Days after Vaccination 2 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.
Percentage of Participants With at Least 1 Adverse Event (AE), Serious Adverse Event (SAE), Medically Attended Adverse Event (MAE), Newly Diagnosed Chronic Medical Condition (NDCMC) and Immediate Adverse Event (IAE) Within 30 Days After Vaccination 3 within 30 Days after Vaccination 3 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.
Percentage of Participants Reporting Systemic Events and Antipyretic Use Within 7 Days After Vaccination 3 within 7 Days after Vaccination 3 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).
Percentage of Participants With at Least 1 Adverse Event (AE), Serious Adverse Event (SAE), Medically Attended Adverse Event (MAE) and Newly Diagnosed Chronic Medical Condition (NDCMC) Within 30 Days After Any Vaccination within 30 Days after any Vaccination 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.
Percentage of Participants With at Least 1 Adverse Event (AE), Serious Adverse Event (SAE), Medically Attended Adverse Event (MAE) and Newly Diagnosed Chronic Medical Condition (NDCMC) During the Vaccination Phase From the Vaccination 1 up to 1 month after Vaccination 3 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.
Percentage of Participants Reporting Systemic Events and Antipyretic Use Within 7 Days After Vaccination 2 within 7 Days after Vaccination 2 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).
Percentage of Participants With at Least 1 Serious Adverse Event (SAE), Medically Attended Adverse Event (MAE) and Newly Diagnosed Chronic Medical Condition (NDCMC) From Vaccination 1 up to 6 Months After Vaccination 3 From Vaccination 1 up to 6 months after Vaccination 3 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.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With hSBA Titer >= LLOQ for Each of the 4 Primary MnB Test Strains 1 Month After Vaccination 2 1 month (Mon) after Vaccination (Vac) 2 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).
Percentage of Participants With at Least 1 Adverse Event (AE) From Booster Vaccination to 1 Month After Booster Vaccination Booster vaccination up to 1 month after booster vaccination An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship.
Percentage of Participants With Serum Bactericidal Assay Using hSBA Titers >=1:4, >=1:8, >=1:16, >=1:32, >=1:64 and >=1:128 for Each of the 4 Primary Test Strains 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) Percentage of Participants With hSBA Titer Between 12 Months to Less Than (<) 24 Months >= LLOQ for Each of the 4 Primary MnB Test Strains at 1, 6, 12, and 24 Months After Vaccination 3 1, 6, 12, 24 months after Vaccination 3 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).
Percentage of Participants Reporting Pre-specified Local Reactions Within 7 Days After Booster Vaccination Within 7 days after booster vaccination 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).
Serum Bactericidal Assay Using Human Complement (hSBA) Geometric Mean Titers (GMTs) for Each of the 4 MnB Primary Test Strains at Before Booster Vaccination and 1 Month After Booster Vaccination Before booster vaccination and 1 month after booster vaccination The LLOQ was 1:16 for A22, 1:8 for A56, B24, and B44. Titers below the LLOQ were set to 0.5\*LLOQ for analysis. Titers were expressed in terms of 1/dilution.
Percentage of Participants Reporting Systemic Events and Antipyretic Use Within 7 Days After Booster Vaccination Within 7 days after booster vaccination 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.
Serum Bactericidal Assay Using Human Complement (hSBA) Geometric Mean Titers (GMTs) for Each of the 4 Primary Test Strains 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) Percentage of Participants With Immediate Adverse Event (IAE) After Booster Vaccination Within 30 minutes after booster vaccination Immediate AE was defined as AEs occurring within the first 30 minutes after investigational product administration.
Percentage of Participants With SAE, MAE, NDCMC From Booster Vaccination to 1 Month After Booster Vaccination, 1 Month After Booster Vaccination to 6 Months After Booster Vaccination and Booster Vaccination Through 6 Months After Booster Vaccination 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) 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.
Percentage of Participants With hSBA Titer >=LLOQ >=1:4, >=1:8, >=1:16, >=1:32, >=1:64 and >=1:128 for Each of the 4 Primary Test Strains Before Booster Vaccination, and 1 Month After Booster Vaccination Before booster vaccination and 1 month after booster vaccination 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.
Trial Locations
- Locations (25)
The Canberra Hospital
🇦🇺Canberra, Garran, Australian Capital Territory, Australia
Vaccine Trials Group, Telethon Kids Institute, Perth Children's Hospital
🇦🇺Nedlands, Western Australia, Australia
Australian Clinical Research Network (ACRN)
🇦🇺Maroubra, New South Wales, Australia
Murdoch Children's Research Institute
🇦🇺Parkville, Victoria, Australia
Maroubra Medical Centre
🇦🇺Maroubra, New South Wales, Australia
Women's And Children's Hospital
🇦🇺North Adelaide, South Australia, Australia
Medicentrum 6 s.r.o
🇨🇿Praha 6 - Vokovice, Czechia
Prakticky Lekar Pro Deti A Mladez
🇨🇿Tynec Nad Sazavou, Czechia
Samostatna ordinace praktickeho lekare pro deti a dorost
🇨🇿Jindrichuv Hradec, Czechia
Ordinace praktickeho lekare pro deti a dorost
🇨🇿Jindrichuv Hradec, Czechia
Espoo Vaccine Research Clinic
🇫🇮Espoo, Finland
Helsinki South Vaccine Research Clinic
🇫🇮Helsinki, Finland
Jarvenpaa Vaccine Research Center
🇫🇮Jarvenpaa, Finland
Helsinki East Vaccine Research Clinic
🇫🇮Helsinki, Finland
Pori Vaccine Research Clinic
🇫🇮Pori, Finland
Tampere Vaccine Research Clinic
🇫🇮Tampere, Finland
NZOZ Vitamed
🇵🇱Bydgoszcz, Poland
Turku Vaccine Research Clinic
🇫🇮Turku, Finland
Specjalistyczna Praktyka Lekarska GRAVITA
🇵🇱Lodz, Poland
Prywatny Gabinet Lekarski dr n. med. Jerzy Brzostek
🇵🇱Debica, Poland
Indywidualna Specjalistyczna Praktyka Lekarska Hanna Czajka
🇵🇱Krakow, Poland
Niepubliczny Zaklad Lecznictwa Ambulatoryjnego Michalkowice Jarosz i Partnerzy Spolka Lekarska
🇵🇱Siemianowice Slaskie, Poland
NZOZ Praktyka Lekarza Rodzinnego Eskulap sp. z o.o
🇵🇱Lublin, Poland
Szpital im. Sw. Jadwigi Slaskiej w Trzebnicy Oddzial Pediatryczny
🇵🇱Trzebnica, Poland
Uniwersytecki Szpital Kliniczny im. J. Mikulicza-Radeckiego we Wroclawiu Klinika Pediatrii i Chorob
🇵🇱Wroclaw, Poland