Immunogenicity and Safety of a Booster Dose of an Investigational Quadrivalent Meningococcal Conjugate Vaccine

Meningitis Clinical Trial

Official title:

Immunogenicity and Safety of a Booster Dose of an Investigational Quadrivalent Meningococcal Conjugate Vaccine in Adolescents and Adults

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02752906
• Other study ID #: MET56
• Secondary ID: U1111-1161-27102
• Status: Completed
• Phase: Phase 3
• Start date: April 15, 2016
• Est. completion date: December 19, 2016

Study information

• Verified date: March 2022
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of the study was to describe the safety and antibody response to booster administration with Meningococcal Polysaccharide (Serogroups A, C, Y and W) Tetanus Toxoid (MenACYW) Conjugate vaccine in participants who received their first quadrivalent meningococcal Conjugate vaccine dose in the past 4-10 years.

Primary Objective:

• To demonstrate the non-inferiority of the vaccine seroresponse of meningococcal serogroups A, C, Y, and W following the administration of a booster dose of MenACYW Conjugate vaccine compared to those observed following the administration of a booster dose of Menactra® in participants who were first vaccinated with 1 dose of a quadrivalent meningococcal vaccine 4 to 10 years before the booster dose.

Secondary Objectives:

• To evaluate the vaccine seroresponse of meningococcal serogroups A, C, Y, and W measured using human serum bactericidal assay (hSBA) in serum specimens collected 6 days after vaccination in a subset of 120 participants.

• To evaluate the antibody responses (geometric mean titers) to serogroups A, C, Y, and W measured using hSBA on Day 0 (pre-vaccination) and Day 30 after vaccination.

Observational Objectives:

• To describe the antibody titers against meningococcal serogroups A, C, Y, and W measured by hSBA assessed at Day 0, Day 6, and Day 30 days after vaccination.

• To describe the antibody responses to the meningococcal serogroups A, C, Y, and W before and 30 days after vaccination with MenACYW Conjugate vaccine or Menactra® measured by rabbit serum bactericidal assay (rSBA) in a subset of participants.

• To describe the safety profile of MenACYW Conjugate vaccine compared to that of a licensed Menactra® after booster vaccination.

Description:

Healthy adolescents and adults who had received 1 dose of a quadrivalent meningococcal Conjugate vaccine 4 to 10 years previously were randomized to receive either 1 dose of MenACYW Conjugate vaccine or licensed Menactra®. All participants underwent immunogenicity assessment at baseline (pre-vaccination) and post-vaccination and were also evaluated for safety up to Day 180 post-vaccination. In addition, a subset had an additional blood sample collected at 6 days post-vaccination for immunogenicity assessment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 810
• Est. completion date: December 19, 2016
• Est. primary completion date: December 19, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 15 Years and older

Eligibility

Inclusion Criteria:

• Aged >= 15 years on the day of inclusion.

• Participant has documented record of having received 1 dose of a quadrivalent meningococcal conjugate vaccine 4 to 10 years prior to study vaccination.

• Participant aged 15 to < 18 years: assent form signed and dated by the participant and informed consent form (ICF) signed and dated by the parent or guardian.

• Participant aged >=18 years: ICF signed and dated by the participant.

• Participants aged 15 to < 18 years: both the participant and parent / guardian were able to attend all scheduled visits and to comply with all trial procedures.

• Participants aged >= 18 years: able to attend all scheduled visits and to comply with all trial procedures.

Exclusion Criteria:

• Participant was pregnant, lactating, or of childbearing potential (to be considered of non-childbearing potential, a female must be pre-menarche or post-menopausal for at least 1 year, surgically sterile, or using an effective method of contraception or abstinence from at least 4 weeks prior to vaccination until at least 4 weeks after vaccination).

• Participation in the 4 weeks preceding the trial vaccination or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure.

• Receipt of any vaccine in the 4 weeks (28 days) preceding the trial vaccination or planned receipt of any vaccine before Day 30 visit except for influenza vaccination, which may be received at least 2 weeks before study investigational vaccines. This exception includes monovalent pandemic influenza vaccines and multivalent influenza vaccines.

• Previous vaccination against meningococcal disease with either an investigational or approved meningococcal B vaccine.

• Receipt of immune globulins, blood or blood-derived products in the past 3 months.

• Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months).

• History of meningococcal infection, confirmed either clinically, serologically, or microbiologically.

• At high risk for meningococcal infection during the trial (specifically, but not limited to, participants with persistent complement deficiency, with anatomic or functional asplenia, or participants travelling to countries with high endemic or epidemic disease).

• Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccine(s) used in the trial or to a vaccine containing any of the same substances.

• Personal history of an Arthus-like reaction after vaccination with a tetanus toxoid-containing vaccine.

• Personal history of Guillain-Barré syndrome.

• Verbal report of thrombocytopenia, contraindicating intramuscular vaccination in the Investigator's opinion.

• Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination in the Investigator's opinion.

• Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily.

• Current alcohol abuse or drug addiction.

• Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion.

• Moderate or severe acute illness/infection (according to the Investigator's judgment) on the day of vaccination or febrile illness (temperature >= 100.4°Fahrenheit [F]). A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided.

• Receipt of oral or injectable antibiotic therapy within 72 hours prior to the first blood draw.

• Identified as an Investigator or employee of the Investigator or study center with direct involvement in the proposed study, or identified as an immediate family member (i.e., parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study.

Related Conditions & MeSH terms

• Meningitis
• Meningitis, Meningococcal
• Meningococcal Infections
• Meningococcal Meningitis

Intervention

Biological:
• Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine
0.5 milliliter (mL), Intramuscular
• Meningococcal (Groups A, C, Y and W 135) Polysaccharide Diphtheria Toxoid Conjugate Vaccine
0.5 mL, Intramuscular

Locations

Country	Name	City	State
Puerto Rico	Investigational Site Number 030	San Juan
United States	Investigational Site Number 013	Bardstown	Kentucky
United States	Investigational Site Number 016	Birmingham	Alabama
United States	Investigational Site Number 019	Cincinnati	Ohio
United States	Investigational Site Number 032	Dothan	Alabama
United States	Investigational Site Number 005	Downey	California
United States	Investigational Site Number 009	Erie	Pennsylvania
United States	Investigational Site Number 011	Fairfield	Ohio
United States	Investigational Site Number 012	Fargo	North Dakota
United States	Investigational Site Number 007	Hermitage	Pennsylvania
United States	Investigational Site Number 025	Huber Heights	Ohio
United States	Investigational Site Number 022	Jonesboro	Arkansas
United States	Investigational Site Number 008	Kansas City	Missouri
United States	Investigational Site Number 021	Kettering	Ohio
United States	Investigational Site Number 014	La Puente	California
United States	Investigational Site Number 023	Lincoln	Nebraska
United States	Investigational Site Number 026	Mesa	Arizona
United States	Investigational Site Number 015	Metairie	Louisiana
United States	Investigational Site Number 027	Nicholasville	Kentucky
United States	Investigational Site Number 031	Omaha	Nebraska
United States	Investigational Site Number 006	Rochester	New York
United States	Investigational Site Number 028	Saint Louis	Missouri
United States	Investigational Site Number 003	Salt Lake City	Utah
United States	Investigational Site Number 020	Salt Lake City	Utah
United States	Investigational Site Number 001	San Diego	California
United States	Investigational Site Number 029	San Diego	California
United States	Investigational Site Number 017	South Jordan	Utah
United States	Investigational Site Number 010	Troy	Michigan
United States	Investigational Site Number 024	Tullahoma	Tennessee
United States	Investigational Site Number 018	Woburn	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi Pasteur, a Sanofi Company

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (1)

Áñez G, Hedrick J, Simon MW, Christensen S, Jeanfreau R, Yau E, Pan J, Jordanov E, Dhingra MS. Immunogenicity and safety of a booster dose of a quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT) in adolescents and adults: a Phase III — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Seroresponse to Meningococcal Serogroups A, C, Y, and W Following Vaccination With Either MenACYW Conjugate Vaccine or Menactra® Vaccine	The serum bactericidal assay using human complement (hSBA) vaccine seroresponse for serogroups A, C, Y, and W was defined as post-vaccination hSBA titers >= 1:16 for participants with pre-vaccination hSBA titers < 1:8 or at least a 4-fold increase in hSBA titers from pre- to post-vaccination for participants with pre-vaccination hSBA titers >= 1:8.	Day 30 (post-vaccination)
Secondary	Percentage of Participants With Seroresponse to Meningococcal Serogroups A, C, Y, and W Following Vaccination With Either MenACYW Conjugate Vaccine or Menactra® Vaccine at Day 6 After Vaccination	The hSBA vaccine seroresponse for serogroups A, C, Y, and W was defined as post-vaccination hSBA titers >= 1:16 for participants with pre-vaccination hSBA titers < 1:8 or at least a 4-fold increase in hSBA titers from pre- to post-vaccination for participants with pre-vaccination hSBA titers >= 1:8.	Day 6 (post-vaccination)
Secondary	Geometric Mean Titers Against Meningococcal Serogroups A, C, Y, and W Antibodies Following Vaccination With Either MenACYW Conjugate Vaccine or Menactra® Vaccine	Meningococcal antibody responses against Serogroups A, C, Y, and W were measured by hSBA.	Day 30 (post-vaccination)
Secondary	Number of Participants With Solicited Injection Site Reactions or Systemic Reactions Following Vaccination With Either MenACYW Conjugate Vaccine or Menactra® Vaccine	A Solicited Reaction (SR) was an Adverse Event (AE) that was prelisted (i.e., solicited) in the electronic case report form (eCRF) and considered to be related to vaccination (adverse drug reaction). Solicited injection site reactions: Pain (Grade 1: no interference with activity, Grade 2: some interference with activity, Grade 3: significantly prevent daily activity), erythema and swelling (Grade 1: >=25 millimeter [mm] to <= 50 mm, Grade 2: >=51 to <=100 mm, Grade 3: > 100 mm). Solicited systemic reactions: Fever (Grade 1: >=38.0 degree Celsius (°C) to <=38.4°C, Grade 2: >=38.5°C to <=38.9 °C, Grade 3: >= 39°C), headache, malaise, and myalgia (Grade 1: no interference with activity, Grade 2: some interference with activity, Grade 3: significant; prevents daily activity. Number of participants with any of the Grade (1, 2 or 3) and with each Grade (1, 2 and 3) solicited injection-site and systemic reactions were reported.	Within 7 days post-vaccination