Immunogenicity and Safety of a Meningococcal Conjugate Vaccine Given Concomitantly With Other Vaccines in Toddlers

Meningitis, Meningococcal Clinical Trial

Official title:

Immunogenicity and Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine Administered Concomitantly With Other Pediatric Vaccines in Healthy Toddlers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03205371
• Other study ID #: MET57
• Secondary ID: U1111-1161-2787
• Status: Completed
• Phase: Phase 3
• Start date: November 7, 2016
• Est. completion date: July 19, 2018

Study information

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

Clinical Trial Summary

This Phase III, open-label, randomized, parallel-group, active-controlled, multicenter study was conducted to assess the immunogenicity and safety of a single dose of Meningococcal Polysaccharide (Serogroups A, C, Y and W) Tetanus Toxoid (MenACYW) Conjugate vaccine when administered alone and in combination with other pediatric vaccines in healthy toddlers in South Korea, Thailand, the Russian Federation, and Mexico. Primary Objective: - To describe the immunogenicity profile of MenACYW Conjugate vaccine administered alone or concomitantly with licensed pediatric vaccine(s) (measles-mumps-rubella vaccine [MMR] + Varicella, diphtheria, tetanus, acellular pertussis, hepatitis B, poliomyelitis, and Haemophilus influenzae type-b Conjugate vaccine [DTaP-IPV-HB-Hib], or pneumococcal Conjugate vaccine [PCV13]). Secondary Objective: - To describe the immunogenicity profile of licensed pediatric vaccine(s) (MMR + Varicella, DTaP-IPV-HB-Hib, or PCV13) when administered alone or concomitantly with MenACYW Conjugate vaccine.

Description:

Healthy, meningococcal-vaccine naïve toddlers aged 12 to 23 months were randomized either to a single dose of MenACYW Conjugate vaccine alone or in combination with other pediatric vaccines in healthy toddlers in South Korea and Thailand (MMR + varicella vaccine), the Russian Federation (PCV13), and Mexico (DTaP-IPV-HB-Hib). Immunogenicity (pre- and 30 days post-vaccination) and safety was assessed.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1183
• Est. completion date: July 19, 2018
• Est. primary completion date: July 19, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 12 Months to 23 Months

Eligibility

Inclusion Criteria:

• For South Korea: Korean males and females aged 12 to 23 months on the day of the first study visit.
• For Mexico: Males and females aged 12 to 23 months on the day of the first study visit.
• For the Russian Federation: Males and females aged 12 to 14 months or 16 to 23 months on the day of the first study visit (eligible for enrollment to MenACYW Conjugate vaccine group) or 15 to 23 months on the day of the first study visit (eligible for enrollment to the MenACYW Conjugate vaccine positive(+) PCV13 group or the PCV13 group).
• For Thailand: Thai males and females aged 12 to 23 months on the day of the first study visit
• Participants had received all recommended standard of care vaccinations according to their age as per local regulations*.
• For the Russian Federation only, participants aged 15 to 23 months on the day of the first study visit (eligible for enrollment to MenACYW Conjugate vaccine+PCV13 group or the PCV13 group) must not had received the third PCV13 vaccination corresponding to his or her age as per the country's National Immunization Program (NIP). The 2nd dose of PCV13 must had been administered at least 4 weeks before the 3rd dose of PCV13 was administered in the study.
• For South Korea, participants must not had received the MMR or Varicella vaccination corresponding to his or her age at inclusion.
• For Mexico, participants must not had received the DTaP-IPV-HB-Hib vaccination corresponding to his or her age at inclusion.
• For Thailand, participants must not have received the any dose of MMR or V vaccination.
• Informed consent form was signed and dated by the parent(s) or guardian if allowed by local regulations (and by independent witnesses if required by local regulations)†.
• Participant and parent/guardian were able to attend all scheduled visits and to comply with all trial procedures.
• *Participants must had received the total number of doses expected for each vaccine recommended for his/her age in the respective NIPs, but inclusion of participants with variations in the vaccine administration timeframes is considered acceptable if the total number of doses for the corresponding vaccines had been completed (e.g., in Mexico, 3 infant doses of the pentavalent vaccine must had been administered but the 4th dose due in the 2nd year of life should not had been administered for participants to be included in the trial). For the Russian Federation only, participants that had not received a seasonal flu vaccination from 6 months of age according to the Russian NIP were still eligible to participate in this study. For Thailand only, participants who had received a vaccine ahead of the schedule can still be included in the study provided the first doses of MMR and Varicella vaccines have not been administered prior to inclusion.
• †In the Russian Federation, as per local regulations, only the participant's parent(s) are entitled to sign an informed consent form. A child under the responsibility of a guardian were not included in the study.

Exclusion Criteria:

• Participation in the 4 weeks preceding the first 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 first trial vaccination or planned receipt of any vaccine prior to Visit 2 except for influenza vaccination, which may be received at least 2 weeks before or after the study investigational vaccines. This exception includes monovalent pandemic influenza vaccines and multivalent influenza vaccines.
• Previous vaccination against meningococcal disease with either the trial vaccine or another vaccine (i.e., mono- or polyvalent, polysaccharide, or conjugate meningococcal vaccine containing serogroups A, C, Y, or W; or meningococcal B vaccine).
• For participants enrolled at sites in the Russian Federation: previous vaccination with the third dose of PCV13 in participants 15 to 23 months of age (eligible for MenACYW Conjugate vaccine+PCV13 group or the PCV13).
• For participants enrolled at sites in Mexico: known history of seizures, or uncontrolled neurologic disorder (including epilepsy); or encephalopathy of unknown etiology occurring within 7 days following previous vaccination with pertussis containing vaccine; previous vaccination with DTaP-IPV-HB-Hib or DTaP-containing vaccine at 12 to 23 months of age.
• For participants enrolled at sites in South Korea and Thailand: known history of seizures, cerebral injury, or encephalopathy; previous vaccination with MMR or Varicella at 12 to 23 months of age.
• 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, according to the Investigator's judgment (specifically, but not limited to, participants with persistent complement deficiency, with anatomic or functional asplenia, or participants traveling 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.
• Verbal report of thrombocytopenia, as reported by the parent/guardian, contraindicating intramuscular (IM) vaccination by the Investigator's judgment.
• Known bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating IM vaccination by the Investigator's judgment.
• Personal history of Guillain-Barré syndrome (GBS).
• Personal history of an Arthus-like reaction after vaccination with a tetanus toxoid-containing vaccine.
• Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion.
• For participants enrolled at sites in South Korea or Mexico and Thailand: Moderate or severe acute illness/infection (according to investigator's judgment) on the day of vaccination or febrile illness (temperature >= 38.0 degree Celsius [°C]). A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided.
• For participants enrolled at sites in the Russian Federation: Acute disease of any severity on the day of vaccination or febrile illness (axillary temperature >= 37.0°C). A prospective participant should not be included in the study until the condition has resolved or the febrile event had subsided.
• Receipt of oral or injectable antibiotic therapy within 72 hours prior to the first blood draw.
• Identified as a natural or adopted child of the Investigator or employee with direct involvement in the proposed study.

Related Conditions & MeSH terms

• Meningitis
• Meningitis, Meningococcal

Intervention

Biological:
• MenACYW conjugate vaccine
Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine; 0.5 milliliter (mL), Intramuscular
• MMR
Measles, Mumps, and Rubella Virus Vaccine Live; 0.5 mL, Subcutaneous
• Varicella
Varicella Virus Vaccine Live; 0.5 mL, Subcutaneous
• DTaP-IPV-HB-Hib
Diphtheria, Tetanus, Pertussis (acellular component), Hepatitis B, Poliomyelitis (inactivated), and Haemophilus influenzae type-b conjugate vaccine (adsorbed); 0.5 mL, Intramuscular
• PCV13
Pneumococcal 13-valent Conjugate Vaccine; 0.5 mL, Intramuscular

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi Pasteur, a Sanofi Company

Countries where clinical trial is conducted

Korea, Republic of,  Mexico,  Russian Federation,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Geometric Mean Titers of Meningococcal Serogroups A, C, Y, and W Antibodies Following Injection With MenACYW Conjugate Vaccine Administered Alone or Concomitantly With Other Pediatric Vaccines: Groups 1, 2, 4, 5, 7, 8, 10, and 11	Antibody titers of Meningococcal Serogroups A, C, Y, and W were measured by serum bactericidal assay using human complement (hSBA) assay. Data for this outcome measure was planned to reported for the combined population of Groups 1 and 10, Groups 2 and 11.	Day 0 and Day 30 post-vaccination
Primary	Percentage of Participants With Antibody Titers >=1:4 and >=1:8 Against Meningococcal Serogroups A, C, Y, and W Following Injection With MenACYW Conjugate Vaccine Administered Alone or With Other Pediatric Vaccines: Groups 1, 2, 4, 5, 7, 8, 10, and 11	Antibody titers of Meningococcal Serogroups A, C, Y, and W were measured by hSBA assay. Data for this outcome measure was planned to be reported for the combined population of Groups 1 and 10, Groups 2 and 11.	Day 0 and Day 30 post-vaccination
Primary	Percentage of Participants With >=4-Fold Rise in Antibody Titers Against Meningococcal Serogroups A, C, Y, and W Following Injection With MenACYW Conjugate Vaccine Administered Alone or With Other Pediatric Vaccines: Groups 1, 2, 4, 5, 7, 8, 10, and 11	Antibody titers of Meningococcal Serogroups A, C, Y, and W were measured by hSBA assay. Data for this outcome measure was planned to be reported for the combined population of Groups 1 and 10, Groups 2 and 11.	Day 0 up to Day 30 post-vaccination
Primary	Percentage of Participants Achieving hSBA Vaccine Seroresponse for Meningococcal Serogroups A, C, Y, and W Following Injection With MenACYW Conjugate Vaccine Administered Alone or Concomitantly With Pediatric Vaccines: Groups 1, 2, 4, 5, 7, 8, 10, and 11	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 titers <1:8 or at least a 4-fold increase in post-vaccination hSBA titers from pre- to post-vaccination, for participants with pre-vaccination titers >=1:8. Data for this outcome measure was planned to be reported for the combined population of Groups 1 and 10, Groups 2 and 11.	Day 30 post-vaccination
Secondary	Geometric Mean Titers of MMR-Varicella Antibodies Following Injection With MMR-Varicella Vaccine Administered Alone or Concomitantly With the MenACYW Conjugate Vaccine: Groups 1, 3, 10, and 12	Antibodies titers of Measles and Rubella were measured by enzyme immunoassay (EIA). Antibodies titers for mumps and varicella were measured by enzyme-linked immunosorbent assay (ELISA). Data for this outcome measure was planned to be reported for the combined population of Groups 1 and 10, Groups 3 and 12.	Day 0 and Day 30 post-vaccination
Secondary	Percentage of Participants With Immune Response Following Injection With MMR-Varicella Vaccine Administered Alone or Concomitantly With the MenACYW Conjugate Vaccine: Groups 1, 3, 10, and 12	Immune response for MMR-Varicella vaccine was defined as: anti-measles Antibody (Ab) concentrations >=255 milli-international unit per milliliter (mIU/mL), anti-mumps Ab concentrations: >=10 Ab units/mL, anti-rubella Ab concentrations >=10 international unit per milliliter (IU/mL),anti-varicella Ab concentrations >=5 glycoprotein enzyme-linked immunosorbent assay (gpELISA) Ab units/mL. Data for this outcome measure was planned to be reported for the combined population of Groups 1 and 10, Groups 3 and 12.	Day 0 and Day 30 post-vaccination
Secondary	Geometric Mean Titers of Pertussis Toxoid (PT) and Filamentous Hemagglutinin (FHA) Antibodies Following Injection With DTaP-IPV-HB-Hib Vaccine Administrated Alone or Concomitantly With the MenACYW Conjugate Vaccine: Groups 4 and 6	Antibodies titers of PT and FHA were measured by electrochemiluminescent (ECL) assay.	Day 0 and Day 30 post-vaccination
Secondary	Geometric Mean Titers of DTaP-IPV-HB-Hib Antibodies Following Injection With DTaP-IPV-HB-Hib Administered Alone or Concomitantly With the MenACYW Conjugate Vaccine: Groups 4 and 6	Antibodies titers of Diphtheria, Tetanus and Pertussis were measured by ECL assay. Antibodies titers of poliovirus types 1, 2, and 3 were measured by neutralization assay. Antibodies titers of Hepatitis B were measured by an immunodiagnostic system using chemiluminescence detection. Antibodies titers of Polyribosyl-ribitol phosphate (PRP) were measured by Farr-type radioimmunoassay (RIA).	Day 0 (for tetanus only) and Day 30 post-vaccination
Secondary	Percentage of Participants With Immune Response Following Injection With DTaP-IPV-HB-Hib Vaccine Administered Alone or Concomitantly With the MenACYW Conjugate Vaccine: Groups 4 and 6	Immune response for DTaP-IPV-HB-Hib vaccine was defined as: anti-tetanus Ab concentrations: >= 0.01 and 0.1 IU/mL at Day 0 and >= 0.1 and 1.0 IU/mL at Day 30, anti-diphtheria Ab concentrations: >= 0.1 and 1.0 IU/mL, anti-PRP Ab concentrations >= 0.15 and 1.0 microgram per milliliter (mcg/mL), anti-poliovirus types 1, 2, and 3 Ab titers >= 1:8, anti-hepatitis B surface antigen Ab concentrations >= 10 mIU/mL, >= 100 mIU/mL.	Day 0 (tetanus only) and Day 30 post-vaccination
Secondary	Percentage of Participants With Vaccine Response of PT and FHA Antibodies Following Injection With DTaP-IPV-HB-Hib Vaccine Administered Alone or Concomitantly With the MenACYW Conjugate Vaccine: Groups 4 and 6	Pertussis and FHA vaccine response was defined as: if the pre-vaccination concentration is < 4 * lower limit of quantification (LLOQ is equal to 2), then the post-vaccination concentration is >=4 * pre-vaccination concentration and if the pre-vaccination concentration is >= 4 * LLOQ, then the post-vaccination concentration is >= 2 * pre-vaccination concentration.	Day 0 and Day 30 post-vaccination
Secondary	Geometric Mean Titers of PCV13 Serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F Antibodies Following Injection With PCV13 Vaccine Administrated Alone or Concomitantly With the MenACYW Conjugate Vaccine: Groups 7 and 9	Antibodies of pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F were measured by ECL assay.	Day 0 and Day 30 post-vaccination
Secondary	Percentage of Participants With Immune Response Following Injection With PCV13 Vaccine Administered Alone or Concomitantly With the MenACYW Conjugate Vaccine: Groups 7 and 9	Immune response for PCV13 for serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F was defined as: antibodies concentrations >=0.35 mcg/mL or >=1.0 mcg/mL.	Day 0 and Day 30 post-vaccination
Secondary	Number of Participants Reporting at Least One Solicited Injection Site Reactions (Tenderness, Erythema, and Swelling): Groups 1, 2, 3, 10, 11, and 12	Solicited Reaction (SR) was defined as 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: tenderness, erythema, and swelling. Tenderness: Grade 3: cries when injected limb moved or the movement of the injected limb reduced, Erythema and swelling: Grade 3: >= 50 millimeter (mm). Participants with any of the Grade and Grade 3 solicited injection-site reactions were reported.	Within 7 days post vaccination
Secondary	Number of Participants Reporting at Least One Solicited Injection Site Reactions (Tenderness, Erythema, and Swelling): Groups 4, 5, and 6	SR was defined as an AE that was prelisted (i.e., solicited) in the eCRF and considered to be related to vaccination (adverse drug reaction). Solicited injection site reactions: tenderness, erythema, and swelling. Tenderness: Grade 3: cries when injected limb moved or the movement of the injected limb reduced, Erythema and swelling: Grade 3: >= 50 mm. Participants with any of the Grade and Grade 3 solicited injection-site reactions were reported.	Within 7 days post vaccination
Secondary	Number of Participants Reporting at Least One Solicited Injection Site Reactions (Tenderness, Erythema, and Swelling): Groups 7, 8, and 9	SR was defined as an AE that was prelisted (i.e., solicited) in the eCRF and considered to be related to vaccination (adverse drug reaction). Solicited injection site reactions: tenderness, erythema, and swelling. Tenderness: Grade 3: cries when injected limb moved, or the movement of the injected limb reduced, Erythema and swelling: Grade 3: >= 50 mm. Participants with any of the Grade and Grade 3 solicited injection-site reactions were reported.	Within 7 days post vaccination
Secondary	Number of Participants Reporting at Least One Solicited Systemic Reactions (Fever, Vomiting, Abnormal Crying, Drowsiness, Appetite Loss, and Irritability)	SR was defined as an AE that was prelisted (i.e., solicited) in the eCRF and considered to be related to vaccination (adverse drug reaction). Solicited systemic reaction: Fever: Grade 3: > 39.5 degree Celsius, Vomiting: Grade 3: >= 6 episodes per 24 hours or requiring parenteral hydration, Crying abnormal: Grade 3: > 3 hours, Drowsiness: Grade 3: sleeping most of the time or difficult to wake up, Appetite lost: Grade 3: refuses >= 3 feeds/meals or refuses most feeds/meals, Irritability: Grade 3: inconsolable. Participants with any of the Grade and Grade 3 solicited systemic reactions were reported.	Within 7 days post vaccination

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