Clinical trial NCT01543087: Duration of hSBA Response After a Primary Series of Bivalent rLP2086 Followed by a Booster Dose
Official title: A PHASE 3 STUDY TO ASSESS THE PERSISTENCE OF HSBA RESPONSE UP TO 48 MONTHS AFTER COMPLETION OF A PRIMARY SERIES OF BIVALENT RLP2086, AND THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A BOOSTER DOSE OF BIVALENT RLP2086
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Meningococcal Infection
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2012-03-02
Enrollment: 698
Sex: ALL
Minimum age (years): 10
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Primary purpose: OTHER

Brief summary: This study is to assess the longevity of immune response in adolescents for approximately 48 months after receipt of a primary series of bivalent rLP2086 vaccination, which is then followed by a booster dose and an assessment of immune response for 12 or 26 months post booster vaccination.

Detailed description: This study is to assess the longevity of immune responses in adolescents (aged 10 to \<19 years at the time of entry into a primary study) following receipt of a vaccination regimen of 2 or 3 doses of bivalent rLP2086 in a primary study. A booster dose of bivalent rLP2086 at approximately 48 months was given following the final dose of the 2- or 3-dose primary bivalent rLP2086 vaccination series. The study was therefore divided into Stage 1 (4-year persistence of immune responses following receipt of a primary vaccination series) and the booster stage (follow-up through 12 months for all boosted or 26 months for a subset of the boosted).

Subjects participating only in Stage 1 will attend up to 6 study visits for collection of a 20-mL blood sample at each visit. Subjects participating in both Stage 1 and booster stage will attend up to 9-10 study visits with 1 visit for booster dose vaccination and 8-9 visits for collection of a 20-mL blood sample at each visit.

Eligibility criteria: Inclusion Criteria for Stage 1:

1. Evidence of a personally signed and dated informed consent document (ICD) indicating that the subject (or a legal representative) has been informed of all pertinent aspects of the study.
2. Subjects who are willing and able to comply with scheduled visits, laboratory tests, and other study procedures.
3. Subjects who completed a primary study and received all the scheduled injections within the originally planned schedule, either with bivalent rLP2086 (either 2 or 3 doses) or with investigational product in cases where subject vaccine assignment is blinded at the time of consent for study B1971033.
4. Subjects who completed the blood draw following the last vaccination and subjects who completed the 6-month follow-up telephone call in the primary study.

Inclusion Criteria for Booster Stage Visits 7-10 (up to12 month post booster follow up):

1. Evidence of a personally signed and dated ICD indicating that the subject or subject's parent(s)/legal guardian has been informed of all pertinent aspects for Visits 7 to 10 of the booster stage of the study.
2. Subject continues to meet all Stage 1 inclusion and none of the Stage 1 exclusion criteria.
3. Subject is confirmed as having received bivalent rLP2086 in the primary vaccination study.
4. Subject has completed B1971033 Stage 1 and completed the Visit 6 blood draw.
5. Subject is available for the entire period of the booster stage and the subject or subject's parent(s)/legal guardian can be reached by telephone.
6. Healthy subject as determined by medical history, physical examination, and judgment of the investigator.
7. Male and female subjects of childbearing potential and at risk for pregnancy must agree to use a highly effective method of contraception through Visit 10 of the booster stage. A subject is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is sexually active. Refer to Section 4.5 for further information.
8. Negative urine pregnancy test for all female subjects on the day of the booster dose.

Inclusion Criteria for Booster Stage Visit11 (26 month post booster follow up):

1. For subject participating in Visit 11, evidence of a personally signed and dated ICD indicating that the subject or subject's parent(s)/legal guardian has been informed of all pertinent aspects of Visit 11.
2. Subject continues to meet all Stage 1 inclusion and none of the Stage 1 exclusion criteria.
3. Subject must have received 2 or 3 doses of bivalent rLP2086 in the primary study on a 0-, 2-, and 6-month or a 0- and 6-month schedule.
4. Subject must have completed booster vaccination at Visit 7.

Exclusion Criteria for Stage 1:

1. Subjects who are investigational site staff members directly involved in the conduct of the trial and their family members, site staff members otherwise supervised by the investigator, or subjects who are Pfizer employees directly involved in the conduct of the trial.
2. With the exception of the primary study of bivalent rLP2086, participation in other studies within the 1-month (30-day) period before study Visit 1 and/or during study participation. Participation in purely observational studies is permitted.
3. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
4. History of culture-proven disease caused by N meningitidis or Neisseria gonorrhoeae.
5. Bleeding diathesis or condition associated with prolonged bleeding time that would contraindicate blood draw.
6. Receipt of any blood products, including gamma globulin, in the period from 6 months before any study visit.
7. Vaccination with any licensed or experimental meningococcal serogroup B vaccine since being enrolled in the primary Pfizer-sponsored MnB study (other than study vaccines permitted in the primary study).
8. Subjects who were not compliant with primary study eligibility criteria while enrolled in the primary study.

Exclusion Criteria for Booster Stage:

1. Subjects who are scheduled to receive 1 or more doses of a human papillomavirus (HPV) vaccine as part of a 3-dose series during the 28 days after the booster vaccination.
2. A previous anaphylactic reaction to any vaccine or vaccine-related component.
3. Subjects receiving any allergen immunotherapy with a nonlicensed product or receiving allergen immunotherapy with a licensed product and are not on stable maintenance doses.
4. Bleeding diathesis or condition associated with prolonged bleeding time that would contraindicate intramuscular injection.
5. A known or suspected defect 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, those receiving chronic systemic (oral, intravenous, or intramuscular) corticosteroid therapy, or those receiving immunosuppressive therapy. Subjects in the United States with terminal complement deficiency are excluded from participation in this study. Please refer to the study reference manual (SRM) for additional details.
6. Significant neurological disorder or history of seizure (excluding simple febrile seizure).
7. Current chronic use of systemic antibiotics.
8. Current participation in another investigational study. Participation in purely observational studies is acceptable.
9. Received any investigational vaccines, drugs, or devices within 28 days before administration of the booster vaccination.
10. Any neuroinflammatory or autoimmune condition, including, but not limited to, transverse myelitis, uveitis, optic neuritis, and multiple sclerosis.
11. Pregnant female subjects, breastfeeding female subjects, male subjects with partners who are currently pregnant, or male and female subjects of childbearing potential who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol through Visit 10 of the study.

Primary outcomes:
measure: Percentage of Participants in Stage 1 Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains at Month 6 (Visit 1) After Primary Vaccinations
timeFrame: Month 6 (Visit 1 of study B1971033)
measure: Percentage of Participants in Stage 1 Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains at Month 12 (Visit 2) After Primary Vaccinations
timeFrame: Month 12 (Visit 2 of study B1971033)
measure: Percentage of Participants in Stage 1 Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains at Month 18 (Visit 3) After Primary Vaccinations
timeFrame: Month 18 (Visit 3 of study B1971033)
measure: Percentage of Participants in Stage 1 Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains at Month 24 (Visit 4) After Primary Vaccinations
timeFrame: Month 24 (Visit 4 of study B1971033)
measure: Percentage of Participants in Stage 1 Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains at Month 36 (Visit 5) After Primary Vaccinations
timeFrame: Month 36 (Visit 5 of study B1971033)
measure: Percentage of Participants in Stage 1 Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains at Month 48 (Visit 6) After Primary Vaccinations
timeFrame: Month 48 (Visit 6 of study B1971033)
measure: Percentage of Booster Stage Participants Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains 1 Month After Last Vaccination in Primary Study
timeFrame: 1 month after last vaccination in primary study
measure: Percentage of Booster Stage Participants Achieving hSBA Titer Level (>=) Lower Limit of Quantitation for Each of the 4 Primary Strains Before Booster Vaccination (48 Months After Last Vaccination in Primary Study [Visit 6])
timeFrame: Visit 6 of study B1971033 (48 months after last vaccination in primary study)
measure: Percentage of Participants Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains 1 Month After the Booster Vaccination (Visit 8)
timeFrame: Visit 8 (1 month following the booster vaccination on Month 49)
measure: Percentage of Participants Achieving hSBATiter Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains 12 Months After the Booster Vaccination(Visit 10)
timeFrame: Visit 10 (12 months following the booster vaccination on Month 60)
measure: Percentage of Participants Achieving hSBA Titer Level Greater Than or Equal to(>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains 26 Months After the Booster Vaccination(Visit 11)
timeFrame: Visit 11 (26 months following the booster vaccination on Month 74)
measure: Percentage of Participants Reporting Local Reactions Within 7 Days After Booster Vaccination
timeFrame: Within 7 days after booster vaccination on Month 48
measure: Percentage of Participants Reporting Systemic Events and Antipyretic Use Within 7 Days After Booster Vaccination
timeFrame: Within 7 days after booster vaccination on Month 48
measure: Percentage of Participants With at Least 1 Adverse Event (AE), Serious Adverse Event (SAE), Newly Diagnosed Chronic Medical Condition (NDCMC) and Medically Attended Adverse Event (MAE) From Booster Vaccination Phase (Visit 7 to Visit 8)
timeFrame: From Visit 7 (Month 48) to Visit 8 (Month 49) in Booster stage
measure: Percentage of Participants With at Least 1 Serious Adverse Event (SAE) and Medically Attended Adverse Event (MAE) From Booster Follow-Up Phase (Visit 8 to Visit 9)
timeFrame: Visit 8 (Month 49) to Visit 9 (Month 54) in Booster stage
measure: Percentage of Participants With at Least 1 Serious Adverse Event (SAE) and Medically Attended Adverse Event (MAE) From Booster Vaccination Through 6 Months After Booster Vaccination (Visit 7 to Visit 9)
timeFrame: From Visit 7 (time of booster vaccination, Month 48) to Visit 9 (6 months after booster vaccination, Month 54)
measure: Percentage of Participants With Newly Diagnosed Chronic Medical Condition;(NDCMC) From the 6-Month Safety Telephone Call in the Primary Study Through 48 Months After the Last Dose in the Primary Study (Visit 6 in Stage 1)
timeFrame: Visit 1 of B1971033 (6-month safety telephone call after last dose in primary study) to Visit 6 of B1971033 (6 months after last primary dose to 48 months after last primary dose in primary study)
measure: Percentage of Participants With at Least 1 Newly Diagnosed Chronic Medical Condition (NDCMC) From 1 Month After Booster Vaccination Through 12 Months After Booster Vaccination (Visit 8 to Visit 10)
timeFrame: From Visit 8 (1 month after booster vaccination, Month 49) to Visit 10 (12 months after booster vaccination, Month 60)
measure: Percentage of Participants With at Least 1 Newly Diagnosed Chronic Medical Condition (NDCMC) From Booster Stage Vaccination Through 12 Months After Booster Vaccination (Visit 7 to Visit 10)
timeFrame: From Visit 7 (time of booster vaccination, Month 48) to Visit 10 (12 months after booster vaccination, Month 60)
measure: Percentage of Participants With Newly Diagnosed Chronic Medical Condition (NDCMC) From 1 Month After Booster Vaccination Through 26 Months After Booster Vaccination (Visit 8 to Visit 11)
timeFrame: From Visit 8 (1 month after booster vaccination, Month 49) to Visit 11 (26 months after booster vaccination, Month 74)
measure: Percentage of Participants With Newly Diagnosed Chronic Medical Condition (NDCMC) From Booster Vaccine Through 26 Months After Booster Vaccination (Visit 7 to Visit 11)
timeFrame: From Visit 7 (time of booster vaccination, Month 48) to Visit 11 (26 months after booster vaccination, Month 74)
measure: Percentage of Participants With at Least 1 Immediate Adverse Event (AE) After Booster Vaccination
timeFrame: Within 30 minutes after Booster Vaccination in Month 48
measure: Number of Days Participants Missed Work or School Due to AE From Booster Vaccination Through 6 Months After Booster Vaccination (Visit 7 Through Visit 9)
timeFrame: From Visit 7 (time of booster vaccination, Month 48) Through Visit 9 (6 months after booster vaccination, Month 54)
Secondary outcomes:
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Clinical Research Advantage, Inc. / East Valley Family Physicians, PLC
state: Arizona
city: Chandler
country: United States
facility: Clinical Research Advantage, Inc./ East Valley Family Physicians, PLC
state: Arizona
city: Huntington Beach
country: United States
facility: St. Joseph Heritage Healthcare
state: California
city: Paramount
country: United States
facility: Center For Clinical Trials, LLC
state: California
city: San Diego
country: United States
facility: California Research Foundation
state: California
city: Valley Village
country: United States
facility: Bayview Research Group
state: California
city: Tampa
country: United States
facility: USF Health South Tampa Center for Advanced Healthcare
state: Florida
city: Tampa
country: United States
facility: USF Health
state: Florida
city: Dalton
country: United States
facility: North Georgia Research Clinical Center
state: Georgia
city: Marietta
country: United States
facility: Pediatrics and Adolescent Medicine, PA
state: Georgia
city: Woodstock
country: United States
facility: Pediatrics And Adolescent Medicine, P.A.
state: Georgia
city: Meridian
country: United States
facility: Advanced Clinical Research
state: Idaho
city: Council Bluffs
country: United States
facility: Clinical Research Advantage, Inc.
state: Iowa
city: Augusta
country: United States
facility: Heartland Research Associates, LLC
state: Kansas
city: Bardstown
country: United States
facility: Kentucky Pediatric/Adult Research
state: Kentucky
city: Louisville
country: United States
facility: U of L Pediatrics: Downtown
state: Kentucky
city: Louisville
country: United States
facility: Brownsboro Park Pediatrics
state: Kentucky
city: Louisville
country: United States
facility: Bluegrass Clinical Research, Inc.
state: Kentucky
city: Stevensville
country: United States
facility: Southwestern Medical Clinic Lakeland Healthcare Affiliate
state: Michigan
city: Kansas City
country: United States
facility: The Center For Pharmaceutical Research
state: Missouri
city: Fremont
country: United States
facility: Clinical Research Advantage, Inc. (Prairie Fields Family Medicine, PC)
state: Nebraska
city: Lincoln
country: United States
facility: Midwest Children's Health Research Institute
state: Nebraska
city: Omaha
country: United States
facility: Creighton University Pediatric Infectious Diseases
state: Nebraska
city: Henderson
country: United States
facility: Clinical Research Center of Nevada,LLC
state: Nevada
city: Cleveland
country: United States
facility: Dr. Shelly David Senders MD Inc. dba Senders Pediatrics
state: Ohio
city: Dayton
country: United States
facility: Ohio Pediatric Research Association
state: Ohio
city: Dayton
country: United States
facility: Ohio Pediatrics, Inc
state: Ohio
city: Houston
country: United States
facility: West Houston Clinical Research Service (WHCRS)
state: Texas
city: Salt Lake City
country: United States
facility: J. Lewis Research, Inc. / Foothill Family Clinic
state: Utah
city: Salt Lake City
country: United States
facility: J. Lewis Research, Inc. / Foothill Family Clinic South
state: Utah
city: Salt Lake City
country: United States
facility: BB Holdings, LLC., dba Jean Brown Research
state: Utah
city: South Jordan
country: United States
facility: J. Lewis Research Inc, Jordan River Family Medicine
state: Utah
city: West Jordan
country: United States
facility: Advanced Clinical Research
state: Utah
city: Vancouver
country: United States
facility: The Vancouver Clinic, Inc. PS
state: Washington
city: Monroe
country: United States
facility: Monroe Clinic
state: Wisconsin
city: Monroe
country: United States
facility: Research and Education Association for Clinical Health, Inc.
state: Wisconsin
city: Holice
country: Czechia
facility: Ordinace praktickeho lekare pro deti a dorost
city: Hradec Kralove
country: Czechia
facility: Ordinace praktickeho lekare pro deti a dorost
city: Hradec Kralove
country: Czechia
facility: Ordinace praktickeho lekare pro deti a dorost
city: Hradec Kralove
country: Czechia
facility: Fakultni nemocnice Hradec Kralove
city: Jindrichuv Hradec
country: Czechia
facility: Ordinace praktickeho lekare pro deti a dorost
city: Odolena Voda
country: Czechia
facility: Ordinace praktickeho lekare pro deti a dorost
city: Pardubice
country: Czechia
facility: Ordinace praktickeho lekare pro deti a dorost
city: Pardubice
country: Czechia
facility: Ordinace praktickeho lekare pro deti a dorost
city: Praha - Nusle
country: Czechia
facility: Ordinace praktickeho lekare pro deti a dorost
city: Praha 6
country: Czechia
facility: Ordinace praktickeho lekare pro deti a dorost
city: Sezemice
country: Czechia
facility: Ordinace praktickeho lekare pro deti a dorost
city: Aarhus N
country: Denmark
facility: Aarhus University hospital Skejby
city: Jarvenpaa
country: Finland
facility: Jarvenpaa Vaccine Research Clinic
city: Pori
country: Finland
facility: Pori Vaccine Research Clinic
city: Tampere
country: Finland
facility: Tampere Vaccine Research Clinic
city: Turku
country: Finland
facility: Turku Vaccine Research Clinic
city: Bad Saulgau
country: Germany
facility: Kinder - und Jugendarzt Praxis
city: Bramsche
country: Germany
facility: Kinderarzt Praxis
city: Eskilstuna
country: Sweden
facility: Infektionskliniken Malarsjukhuset
city: Malmo
country: Sweden
facility: Skanes Universitetssjukhus
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Vesikari T, Ostergaard L, Beeslaar J, Absalon J, Eiden JJ, Jansen KU, Jones TR, Harris SL, Maansson R, Munson S, O'Neill RE, York LJ, Perez JL. Persistence and 4-year boosting of the bactericidal response elicited by two- and three-dose schedules of MenB-FHbp: A phase 3 extension study in adolescents. Vaccine. 2019 Mar 14;37(12):1710-1719. doi: 10.1016/j.vaccine.2018.11.073. Epub 2019 Feb 12.