A Clinical Trial to Study the Safety, Tolerance and Immunogenic Response to MCV4, Tdap and Bivalent rLP2086 Vaccine When Given at the Same Time to Children Between the Ages of 10 Through 12 Years of Age

Vaccines Clinical Trial

Official title:

A Phase 2, Randomized, Active-controlled, Observer-blinded Trial, To Assess The Safety, Tolerability, And Immunogenicity Of Mcv4, Tdap Vaccine And Bivalent Rlp2086 Vaccine When Administered Concomitantly In Healthy Subjects Aged > = 10 To <13 Years

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01461980
• Other study ID #: B1971015
• Secondary ID: 6108A1-2005
• Status: Completed
• Phase: Phase 2
• Start date: September 28, 2011
• Est. completion date: May 8, 2014

Study information

• Verified date: November 2018
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a clinical study to assess the safety, tolerance and immunogenic response to MCV4(quadrivalent meningococcal polysaccharide conjugate, meningococcal serogroups A,C,Y, and W135), Tdap (diphtheria, tetanus, and acellular pertussis), and bivalent rLP2086 vaccine. Healthy male and female subjects, between the ages of 10 to 12 years old, will be randomized into 1 of 3 groups. The subjects, investigators, site staff and sponsor will be blinded to all injections given throughout the study. An unblinded administrator will be responsible to administer the vaccinations to all subjects and will be unblinded to the subject randomization in order to determine which subjects were in randomized to group 3 so they may receive their catch-up vaccinations of MCV4 and Tdap. A final telephone contact will be conducted with all subjects 6-months post their last vaccination to obtain safety information.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2648
• Est. completion date: May 8, 2014
• Est. primary completion date: May 8, 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 10 Years to 12 Years

Eligibility

Inclusion Criteria:

• Evidence of a personally signed and dated informed consent document (ICD) indicating that the subject (and a legally authorized representative) has been informed of all pertinent aspects of the study.

• Parent /legally authorized representative and subjects who are willing and able to comply with scheduled visits, laboratory tests, and other study procedures.

• Male or female subject aged greater than or equal to 10 and <13 years at the time of enrollment.

• Available for the entire study period and can be reached by telephone.

• Healthy subject as determined by medical history, physical examination, and judgment of the investigator.

• Has received full series (5-dose series is preferred, 4-dose catch up series is allowed) of diphtheria, tetanus and pertussis (whole cell or acellular) vaccines per country specific recommendations applicable at the time of receipt.

• Male and female subjects of childbearing potential must agree to use a highly effective method of contraception throughout the study.

Exclusion Criteria:

• Previous vaccination with any meningococcal serogroup B vaccine.

• Vaccination with any diphtheria, tetanus or pertussis vaccine within 5 years of the first study vaccination.

• Previous vaccination with any MCV4 vaccine.

• A previous anaphylactic reaction to any vaccine or vaccine-related component.

• Contraindication to vaccination with MCV4 and/or Tdap vaccine.

• Subjects receiving any allergen immunotherapy with a non-licensed product or receiving allergen immunotherapy with a licensed product and are not on stable maintenance doses.

• Bleeding diathesis or condition associated with prolonged bleeding time that would contraindicate intramuscular injection.

• 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 with terminal complement deficiency may not be included.

• History of culture-proven disease caused by Neisseria meningitidis or Neisseria gonorrhoea.

• Significant neurological disorder or history of seizure (excluding simple febrile seizure).

• Receipt of any blood products, including immunoglobulin within 6 months before the first study vaccination.

• Current chronic use of systemic antibiotics.

• Any neuroinflammatory or autoimmune condition, including, but not limited to, transverse myelitis, uveitis, optic neuritis, and multiple sclerosis.

Related Conditions & MeSH terms

• Meningococcal Vaccines
• Vaccines

Intervention

Biological:
• rLP2086 + MCV4 + Tdap
At visit 1, group 1 will receive MCV4 + Tdap vaccines concomitantly with an injection of rLP2086. At visits 3 and 5 (Months 2 and 6), group 1 will receive an injection of rLP2086.
• MCV4 + Tdap + saline
At visit 1, group 2 will receive MCV4 + Tdap vaccines concomitantly with an injection of saline. At visits 3 and 5 (months 2 and 6), this group will receive a saline injection only.
• rLP2086 + saline
At visit 1, group 3 will receive 2 injections of saline concomitantly with an injection of rLP2086. At visits 3 and 5 (Months 2 and 6), group 3 will receive an injection of rLP2086. Subjects randomized to this group will receive MCV4 and Tdap following their final visit blood draw (Visit 6).

Locations

Country	Name	City	State
United States	Radiant Research, Inc	Akron	Ohio
United States	Radiant Research, Inc.	Anderson	South Carolina
United States	Emory University School of Medicine	Atlanta	Georgia
United States	Emory University School of Medicine Department of Pediatrics	Atlanta	Georgia
United States	Radiant Research, Inc	Atlanta	Georgia
United States	Heartland Research Associates, LLC	Augusta	Kansas
United States	Tekton Research, Inc.	Austin	Texas
United States	Kentucky Pediatric/Adult Research	Bardstown	Kentucky
United States	Radiant Research, Inc.	Birmingham	Alabama
United States	Internal Medicine & Pediatric Associates of Bristol, PC	Bristol	Tennessee
United States	PMG Research of Bristol	Bristol	Tennessee
United States	PI-Coor Clinical Research, LLC	Burke	Virginia
United States	Clinical Research Advantage Inc/ East Valley Family Physicians, PLC	Chandler	Arizona
United States	Radiant Research, Inc.	Chandler	Arizona
United States	Charleston Pediatrics	Charleston	South Carolina
United States	Pediatric Associates of Charlottesville, PLC	Charlottesville	Virginia
United States	Pediatric Associates of Charlottesville, PLC - North Satellite	Charlottesville	Virginia
United States	Pediatric Associates of Charlottesville, PLC - West Satellite	Charlottesville	Virginia
United States	Cincinnati Center for Clinical Research, Satellite Site - Clinic	Cincinnati	Ohio
United States	Cincinnati Childrens Hospital Medical Center Gamble Program for Clinical Studies	Cincinnati	Ohio
United States	Dr. Shelly David Senders, MD Inc. dba Senders Pediatrics	Cleveland	Ohio
United States	Rapid Medical Research, Inc.	Cleveland	Ohio
United States	Senders Pediatrics	Cleveland	Ohio
United States	Colorado Springs Family Practice	Colorado Springs	Colorado
United States	Lynn Institute of the Rockies	Colorado Springs	Colorado
United States	Radiant Research	Columbus	Ohio
United States	Clinical Research Advantage, Inc./ Ridge Family Practice, PC	Council Bluffs	Iowa
United States	Office of Richard Ohnmacht	Cranston	Rhode Island
United States	Radiant Research, Inc.	Dallas	Texas
United States	North Georgia Clinical Research Center dba Whites Pediatrics	Dalton	Georgia
United States	Costal Clinical Research, Inc.	Daphne	Alabama
United States	Ohio Pediatric Research Association	Dayton	Ohio
United States	Ohio Pediatrics, Inc.	Dayton	Ohio
United States	Northern Illinois Research Associates	DeKalb	Illinois
United States	Radiant Research, Inc.	Denver	Colorado
United States	Duke Health Center	Durham	North Carolina
United States	Duke University Medical Center - Duke Health Center	Durham	North Carolina
United States	Durham Pediatrics	Durham	North Carolina
United States	Child Health Care Associates	East Syracuse	New York
United States	Christopher Brad Redden, ARNP Healthcare One Urgent Care and Family Practice	El Reno	Oklahoma
United States	Innovis Health	Fargo	North Dakota
United States	Odyssey Research	Fargo	North Dakota
United States	Clinical Research Advantage, Inc. / Prairie Fields Family Medicine, PC	Fremont	Nebraska
United States	Kaiser Permanente Fresno	Fresno	California
United States	Kaiser Permanente Hayward	Hayward	California
United States	Clinical Research Center of Nevada	Henderson	Nevada
United States	Advances in Health Research, Inc	Houston	Texas
United States	Pediatric Healthcare of Northwest Houston	Houston	Texas
United States	Pediatric Healthcare of Northwest Houston	Houston	Texas
United States	Texas Center for Drug Development, Inc.	Houston	Texas
United States	West Houston Clinical Research Service	Houston	Texas
United States	Ohio Pediatrics, Inc.	Huber Heights	Ohio
United States	Pediatric Care Medical Group	Huntington Beach	California
United States	The Children's Clinic of Jonesboro, PA	Jonesboro	Arkansas
United States	The Center for Pharmaceutical Research, PC	Kansas City	Missouri
United States	Ohio Pediatric Research	Kettering	Ohio
United States	Gundersen Clinic, LTD	La Crosse	Wisconsin
United States	Clinical Research Center of Nevada	Las Vegas	Nevada
United States	Midwest Children's Health Research Institute	Lincoln	Nebraska
United States	Arkansas Pediatric Clinic	Little Rock	Arkansas
United States	Loma Linda University	Loma Linda	California
United States	Loma Linda University Health Care Pediatric Clinic	Loma Linda	California
United States	Loma Linda University Medical Center	Loma Linda	California
United States	Bluegrass Clinical Research, Inc.	Louisville	Kentucky
United States	Brownsboro Park Pediatrics	Louisville	Kentucky
United States	University of Louisville Pediatrics: Children and Youth Project	Louisville	Kentucky
United States	Pediatrics and Adolescent Medicine, PA	Marietta	Georgia
United States	Advanced Clinical Research	Meridian	Idaho
United States	Clinical Research Advantage, Inc./Desert	Mesa	Arizona
United States	Clinical Research Advantage, Inc./Mesa Family Medical Center, PC	Mesa	Arizona
United States	Monroe Clinic	Monroe	Wisconsin
United States	Loma Linda University Health Care - Moreno Valley Pediatrics	Moreno Valley	California
United States	PMG Research of Charleson	Mount Pleasant	South Carolina
United States	Radiant Research, Inc.	Murray	Utah
United States	Clinical Research Associates, Inc.	Nashville	Tennessee
United States	Lynn Institute of Norman (LION)	Norman	Oklahoma
United States	Norwich Pediatric Group, P.C.	Norwich	Connecticut
United States	Lynn Health Science Institute	Oklahoma City	Oklahoma
United States	Creighton Pediatric Infectious Diseases Creighton University Medical Center	Omaha	Nebraska
United States	Quality Clinical Research, Inc.	Omaha	Nebraska
United States	Bayview Research Group, LLC	Paramount	California
United States	Center for Clinical Trials, LLC	Paramount	California
United States	PMG Research of Raleigh, LLC	Raleigh	North Carolina
United States	PMG Research of Raleigh, LLC	Raleigh	North Carolina
United States	PMG Research of Raleigh, LLC -	Raleigh	North Carolina
United States	Kaiser Permanente Sacramento	Sacramento	California
United States	Mercy Health Research	Saint Louis	Missouri
United States	Radiant Research, Inc.	Saint Louis	Missouri
United States	Saint Louis University	Saint Louis	Missouri
United States	Sundance Clinical Research, LLC	Saint Louis	Missouri
United States	Allina Health Bandana Square Clinic	Saint Paul	Minnesota
United States	Aspen Medical Group	Saint Paul	Minnesota
United States	Aspen Medical Group/ Odyssey Research	Saint Paul	Minnesota
United States	J. Lewis Resarch Incorporated, Foothill Family Clinic	Salt Lake City	Utah
United States	J. Lewis Research Inc. - Foothill Family Clinic South	Salt Lake City	Utah
United States	Jean Brown Research	Salt Lake City	Utah
United States	Child Care Associates	San Antonio	Texas
United States	Clinical Trials of Texas, Inc.	San Antonio	Texas
United States	First Steps Pediatrics	San Antonio	Texas
United States	Radiant Research, Inc.	San Antonio	Texas
United States	California Research Foundation	San Diego	California
United States	J. Lewis Research, Inc. - Jordan River Family Medicine	South Jordan	Utah
United States	Southwestern Medical Clinic Lakeland Healthcare Affiliate	Stevensville	Michigan
United States	University of South Florida	Tampa	Florida
United States	Pediatric Healthcare of Northwest Houston	Tomball	Texas
United States	Pediatric Healthcare of Northwest Houston, PA	Tomball	Texas
United States	Radiant Research, Inc.	Tucson	Arizona
United States	Radiant Research, Inc.	Tucson	Arizona
United States	Oklahoma State University - Center for Health Sciences - Pediatric Research	Tulsa	Oklahoma
United States	Bayview Research Group, LLC	Valley Village	California
United States	The Vancouver Clinic	Vancouver	Washington
United States	The Vancouver Clinic	Vancouver	Washington
United States	Omega Medical Research	Warwick	Rhode Island
United States	Advanced Clinical Research	West Jordan	Utah
United States	Heartland Research Associates, LLC	Wichita	Kansas
United States	Via Christi Clinic, P.A.	Wichita	Kansas
United States	Pediatrics and Adolescent Medicine	Woodstock	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Immunogloblulin G (IgG) Measured by GMC	IgG GMCs of 4 MCV4 antigens (serogroup A, serogroup C, serogroup Y and serogroup W-135) of participants were computed along with corresponding 2-sided 95% CIs. CIs were back transformations of confidence levels based on Student t distribution for mean logarithm of titers.	Before Vaccination 1, 1 Month after Vaccination 1
Other	Percentage of Participants Achieving at Least 4-Fold Increase in Serum Bactericidal Assay Using Human Complement (hSBA) Titer Level		1 Month after Vaccination (Vac) 2, 3
Other	Percentage of Participants With at Least One Adverse Event (AE)	An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship.	Vaccination phase (baseline up to 1 month after Vaccination 3); Follow-up phase (from 1 month up to 6 months after Vaccination 3)
Primary	Geometric Mean Concentrations (GMC) for Diphtheria and Tetanus Antigens	Antibody GMCs of 2 antigens of diphtheria and tetanus toxoid were computed in International Units per milliliter (IU/mL) along with corresponding 2-sided 95 percent (%) confidence intervals (CIs). Here, 'number of participants analyzed' signifies participants with valid and determinate assay results for given antigen.	1 Month after Vaccination 1
Primary	Geometric Mean Concentrations (GMC) for Acellular Pertussis Antigens	Antibody GMCs of 4 acellular pertussis antigens (pertussis toxoid, pertussis filamentous hemagglutinin, pertussis pertactin and pertussis fimbrial agglutinogens types 2+3) were computed in Enzyme-linked immunosorbent assay (ELISA) units per milliliter (EU/mL) along with corresponding 2-sided 95% CIs.	1 Month after Vaccination 1
Primary	Geometric Mean Titer (GMT) for Meningococcal Conjugate Vaccine (MCV4) Antigens	Antibody GMTs of 4 MCV4 antigens (serogroup A, serogroup C, serogroup Y and serogroup W-135) were computed along with corresponding 2-sided 95% CIs.	1 Month after Vaccination 1
Primary	Serum Bactericidal Assay Using Human Complement (hSBA) GMTs of PMB80 [A22] and PMB2948 [B24] 1 Month After Vaccination 3	Antibody hSBA GMTs of primary strain PMB80 [A22] and PMB2948 [B24] were computed along with corresponding 2-sided 95% CIs. hSBA titers from the 2 primary strains were logarithmically transformed for analysis. Here, 'number of participants analyzed' signifies evaluable immunogenicity population and 'N' signifies participants with valid and determinate assay results for given strain for each group, respectively.	1 Month after Vaccination 3
Secondary	Percentage of Participants With Seroresponse for Tetanus, Diphtheria and Acellular Pertussis (Tdap) and Meningococcal Conjugate Vaccine (MCV4) Antigens	Seroconversion rate for Tdap antigens was defined as greater than or equal to (>=) 4-, 2-fold rise in antibody concentration, if prevaccination antibody concentration was less than or equal to (<=), greater than (>) cutoff value, respectively. For MCV4 antigens >=4-fold rise on serum bactericidal assay using rabbit complement (rSBA) titers if baseline value >= lower limit of quantitation (LLOQ), postdose rSBA titers >=2×LLOQ if baseline value was less than (<) LLOQ. Cutoff value =0.1 IU/mL for diphtheria and tetanus, 0.9,2.9,3.0,10.6 EU/mL for pertussis toxoid, filamentous hemagglutinin, pertactin, fimbriae agglutinogens types 2 + 3, respectively.	1 Month after Vaccination 1
Secondary	Percentage of Participants Achieving Predefined Antibody Level for Diphtheria and Tetanus Antigens	Participants with antibody concentration level of greater than or equal to 1.0 IU/mL for diphtheria and tetanus antigens were computed along with corresponding 2-sided 95% CIs.	1 Month after Vaccination 1
Secondary	Serum Bactericidal Assay Using Human Complement (hSBA) GMTs of PMB80 [A22] and PMB2948 [B24] Before Vaccination 1 and 1 Month After Vaccination 2	Antibody hSBA of primary strain PMB80 [A22] and PMB2948 [B24] were computed along with corresponding 2-sided 95% CIs. hSBA titers from the 2 primary strains were logarithmically transformed for analysis.	Before Vaccination 1, 1 Month after Vaccination (Vac) 2
Secondary	Percentage of Participants With Serum Bactericidal Assay Using Human Complement (hSBA) Titer >= Lower Limit of Quantitation (LLOQ)	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 PMB2948 [B24].	Before Vaccination 1, 1 Month after Vaccination (Vac) 2, 3
Secondary	Percentage of Participants With Serum Bactericidal Assay Using Human Complement (hSBA) Titer >= Prespecified Titer Level	Antibody hSBA of primary strain PMB80 [A22] and PMB2948 [B24] with hSBA titers >=1:4, >=1:8, >=1:16, >=1:32, >=1:64, and >=1:128 were computed along with corresponding 2-sided 95% CIs.	Before Vaccination 1, 1 Month after Vaccination (Vac) 2, 3