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

NCT02534935 | Completed Phase 2 Results DMC

• 2 other identifiers: B19710352011-004400-38
• Study Type: interventional
• Target: 396
• Locations: 4 countries
• Sites: 25

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.

Conditions

Meningococcal B Disease

Keywords

Phase 2 Immunogenicity; Safety; Tolerability Study; rLP2086 Vaccine; Healthy Toddlers; Neisseria meningitidis; Duration of Immunogenicity

Outcome Measures

Primary Outcomes (14)

• 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

  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).

  1 month after Vaccination 3

• Percentage of Participants Reporting Pre-specified Local Reactions 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).

  within 7 Days after Vaccination 1

• Percentage of Participants Reporting Pre-specified Local Reactions 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).

  within 7 Days after Vaccination 2

• Percentage of Participants Reporting Pre-specified Local Reactions 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).

  within 7 Days after Vaccination 3

• Percentage of Participants Reporting Systemic Events and Antipyretic Use 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).

  within 7 Days after Vaccination 1

• Percentage of Participants Reporting Systemic Events and Antipyretic Use 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).

  within 7 Days after Vaccination 2

• Percentage of Participants Reporting Systemic Events and Antipyretic Use 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).

  within 7 Days after Vaccination 3

• 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

  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.

  within 30 Days after Vaccination 1

• 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

  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.

  within 30 Days after Vaccination 2

• 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

  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.

  within 30 Days after Vaccination 3

• 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

  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.

  within 30 Days after any Vaccination

• 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

  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.

  From the Vaccination 1 up to 1 month after Vaccination 3

• 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

  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.

  From 1 month after Vaccination 3 up to 6 months after Vaccination 3

• 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

  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.

  From Vaccination 1 up to 6 months after Vaccination 3

Secondary Outcomes (11)

• 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 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 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)

• 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 Reporting Pre-specified Local Reactions Within 7 Days After Booster Vaccination

  Within 7 days after booster vaccination

Study Arms (2)

rLP2086 vaccine

EXPERIMENTAL

Arm stratified by age: ≥12 to \<18 months and ≥18 to \<24 months

Biological: rLP2086 vaccine

Control

ACTIVE COMPARATOR

Arm stratified by age: ≥12 to \<18 months and ≥18 to \<24 months

Biological: Pediatric HAV vaccine

Interventions

rLP2086 vaccine BIOLOGICAL

60 mcg or 120mcg at 0, 2 and 6 months

rLP2086 vaccine

Pediatric HAV vaccine BIOLOGICAL

0.5-mL dose at months 0 and 6. Normal saline at month 2.

Control

Eligibility Criteria

• Age: 12 Months - 24 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (25)

The Canberra Hospital

Canberra, Garran, Australian Capital Territory, 2605, Australia

Location

Australian Clinical Research Network (ACRN)

Maroubra, New South Wales, 2035, Australia

Location

Maroubra Medical Centre

Maroubra, New South Wales, 2035, Australia

Location

Women's And Children's Hospital

North Adelaide, South Australia, 5006, Australia

Location

Murdoch Children's Research Institute

Parkville, Victoria, 3052, Australia

Location

Vaccine Trials Group, Telethon Kids Institute, Perth Children's Hospital

Nedlands, Western Australia, 6009, Australia

Location

Ordinace praktickeho lekare pro deti a dorost

Jindřichův Hradec, 377 01, Czechia

Location

Samostatna ordinace praktickeho lekare pro deti a dorost

Jindřichův Hradec, 377 01, Czechia

Location

Medicentrum 6 s.r.o

Praha 6 - Vokovice, 160 00, Czechia

Location

Prakticky Lekar Pro Deti A Mladez

Týnec nad Sázavou, 257 41, Czechia

Location

Espoo Vaccine Research Clinic

Espoo, 02230, Finland

Location

Helsinki South Vaccine Research Clinic

Helsinki, 00100, Finland

Location

Helsinki East Vaccine Research Clinic

Helsinki, 00930, Finland

Location

Jarvenpaa Vaccine Research Center

Jarvenpaa, 04400, Finland

Location

Pori Vaccine Research Clinic

Pori, 28100, Finland

Location

Tampere Vaccine Research Clinic

Tampere, 33100, Finland

Location

Turku Vaccine Research Clinic

Turku, 20520, Finland

Location

NZOZ Vitamed

Bydgoszcz, 85-079, Poland

Location

Prywatny Gabinet Lekarski dr n. med. Jerzy Brzostek

Dębica, 39-200, Poland

Location

Indywidualna Specjalistyczna Praktyka Lekarska Hanna Czajka

Krakow, 31-302, Poland

Location

Specjalistyczna Praktyka Lekarska GRAVITA

Lodz, 91-347, Poland

Location

NZOZ Praktyka Lekarza Rodzinnego Eskulap sp. z o.o

Lublin, 20-044, Poland

Location

Niepubliczny Zaklad Lecznictwa Ambulatoryjnego Michalkowice Jarosz i Partnerzy Spolka Lekarska

Siemianowice Śląskie, 41-103, Poland

Location

Szpital im. Sw. Jadwigi Slaskiej w Trzebnicy Oddzial Pediatryczny

Trzebnica, 55-100, Poland

Location

Uniwersytecki Szpital Kliniczny im. J. Mikulicza-Radeckiego we Wroclawiu Klinika Pediatrii i Chorob

Wroclaw, 50-368, Poland

Location

Related Publications (1)

• Marshall HS, Vesikari T, Richmond PC, Wysocki J, Szenborn L, Beeslaar J, Maguire JD, Balmer P, O'Neill R, Anderson AS, Pregaldien JL, Maansson R, Jiang HQ, Perez JL. Safety and immunogenicity of a primary series and booster dose of the meningococcal serogroup B-factor H binding protein vaccine (MenB-FHbp) in healthy children aged 1-9 years: two phase 2 randomised, controlled, observer-blinded studies. Lancet Infect Dis. 2023 Jan;23(1):103-116. doi: 10.1016/S1473-3099(22)00424-8. Epub 2022 Sep 7.

  PMID: 36087588 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

Limitations and Caveats

The immunogenicity data at 36 and 48 months after vaccination 3 was not collected due to change in planned analysis as per latest protocol amendment, according to which blood draw of participants at 36 and 48 months after Vaccination 3 was removed.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2015
• First Posted: August 28, 2015
• Study Start: August 31, 2015
• Primary Completion: August 21, 2017
• Study Completion: March 17, 2020
• Last Updated: September 27, 2021
• Results First Posted: April 17, 2018

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will share

Locations

PL (8); AU (6); CZ (4); FI (7)