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

NCT ID: NCT03205371

Last Updated: 2022-04-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1183 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-07
• Study Completion Date: 2018-07-19

Brief 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.

Detailed 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.

Conditions

Meningitis, Meningococcal

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

South Korea(Group1):MenACYW Conjugate + MMR+ Varicella Vaccine

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) received single dose of MenACYW Conjugate vaccine, MMR vaccine, and varicella vaccine on Day 0.

Group Type: EXPERIMENTAL

MenACYW conjugate vaccine

Intervention Type: BIOLOGICAL

Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine; 0.5 milliliter (mL), Intramuscular

MMR

Intervention Type: BIOLOGICAL

Measles, Mumps, and Rubella Virus Vaccine Live; 0.5 mL, Subcutaneous

Varicella

Intervention Type: BIOLOGICAL

Varicella Virus Vaccine Live; 0.5 mL, Subcutaneous

South Korea (Group 2): MenACYW Conjugate Vaccine

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) received single dose of MenACYW Conjugate vaccine on Day 0.

Group Type: EXPERIMENTAL

MenACYW conjugate vaccine

Intervention Type: BIOLOGICAL

Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine; 0.5 milliliter (mL), Intramuscular

South Korea (Group 3): MMR + Varicella Vaccine

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) received single dose of MMR vaccine and varicella vaccine on Day 0.

Group Type: ACTIVE_COMPARATOR

MMR

Intervention Type: BIOLOGICAL

Measles, Mumps, and Rubella Virus Vaccine Live; 0.5 mL, Subcutaneous

Varicella

Intervention Type: BIOLOGICAL

Varicella Virus Vaccine Live; 0.5 mL, Subcutaneous

Thailand (Group 10):MenACYW Conjugate +MMR+Varicella Vaccine

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) received single dose of MenACYW Conjugate vaccine, MMR vaccine, and varicella vaccine on Day 0.

Group Type: EXPERIMENTAL

MenACYW conjugate vaccine

Intervention Type: BIOLOGICAL

Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine; 0.5 milliliter (mL), Intramuscular

MMR

Intervention Type: BIOLOGICAL

Measles, Mumps, and Rubella Virus Vaccine Live; 0.5 mL, Subcutaneous

Varicella

Intervention Type: BIOLOGICAL

Varicella Virus Vaccine Live; 0.5 mL, Subcutaneous

Thailand (Group 11):MenACYW Conjugate Vaccine

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) received single dose of MenACYW Conjugate vaccine on Day 0.

Group Type: EXPERIMENTAL

MenACYW conjugate vaccine

Intervention Type: BIOLOGICAL

Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine; 0.5 milliliter (mL), Intramuscular

Thailand (Group 12): MMR + Varicella Vaccine

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) received single dose of MMR vaccine and varicella vaccine on Day 0.

Group Type: ACTIVE_COMPARATOR

MMR

Intervention Type: BIOLOGICAL

Measles, Mumps, and Rubella Virus Vaccine Live; 0.5 mL, Subcutaneous

Varicella

Intervention Type: BIOLOGICAL

Varicella Virus Vaccine Live; 0.5 mL, Subcutaneous

Mexico (Group 4): MenACYW Conjugate + DTaP-IPV-HB-Hib Vaccine

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) received single dose of MenACYW Conjugate vaccine and diphtheria, tetanus, acellular pertussis, hepatitis B, poliomyelitis and Haemophilus influenzae type-b (DTaP-IPV-HB-Hib) vaccine on Day 0.

Group Type: EXPERIMENTAL

MenACYW conjugate vaccine

Intervention Type: BIOLOGICAL

Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine; 0.5 milliliter (mL), Intramuscular

DTaP-IPV-HB-Hib

Intervention Type: BIOLOGICAL

Diphtheria, Tetanus, Pertussis (acellular component), Hepatitis B, Poliomyelitis (inactivated), and Haemophilus influenzae type-b conjugate vaccine (adsorbed); 0.5 mL, Intramuscular

Mexico (Group 5): MenACYW Conjugate Vaccine

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) received single dose of MenACYW Conjugate vaccine on Day 0.

Group Type: EXPERIMENTAL

MenACYW conjugate vaccine

Intervention Type: BIOLOGICAL

Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine; 0.5 milliliter (mL), Intramuscular

Mexico (Group 6): DTaP-IPV-HB-Hib Vaccine

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 23 months) received single dose of DTaP-IPV-HB-Hib vaccine on Day 0.

Group Type: ACTIVE_COMPARATOR

DTaP-IPV-HB-Hib

Intervention Type: BIOLOGICAL

Diphtheria, Tetanus, Pertussis (acellular component), Hepatitis B, Poliomyelitis (inactivated), and Haemophilus influenzae type-b conjugate vaccine (adsorbed); 0.5 mL, Intramuscular

Russian Federation (Group7): MenACYW Conjugate + PCV13 Vaccine

Healthy, meningococcal-vaccine naïve toddlers (aged 15 to 23 months) received single dose of MenACYW Conjugate vaccine and pneumococcal Conjugate vaccine (PCV13) on Day 0.

Group Type: EXPERIMENTAL

MenACYW conjugate vaccine

Intervention Type: BIOLOGICAL

Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine; 0.5 milliliter (mL), Intramuscular

PCV13

Intervention Type: BIOLOGICAL

Pneumococcal 13-valent Conjugate Vaccine; 0.5 mL, Intramuscular

Russian Federation (Group 8): MenACYW Conjugate Vaccine

Healthy, meningococcal-vaccine naïve toddlers (aged 12 to 14 months or 16 to 23 months) received single dose of MenACYW Conjugate vaccine on Day 0.

Group Type: EXPERIMENTAL

MenACYW conjugate vaccine

Intervention Type: BIOLOGICAL

Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine; 0.5 milliliter (mL), Intramuscular

Russian Federation (Group 9): PCV13 Vaccine

Healthy, meningococcal-vaccine naïve toddlers (aged 15 to 23 months) received single dose of PCV13 vaccine on Day 0.

Group Type: ACTIVE_COMPARATOR

PCV13

Intervention Type: BIOLOGICAL

Pneumococcal 13-valent Conjugate Vaccine; 0.5 mL, Intramuscular

Interventions

MenACYW conjugate vaccine

Meningococcal Polysaccharide (Serogroups A, C, Y, and W) Tetanus Toxoid Conjugate Vaccine; 0.5 milliliter (mL), Intramuscular

Intervention Type: BIOLOGICAL

MMR

Measles, Mumps, and Rubella Virus Vaccine Live; 0.5 mL, Subcutaneous

Intervention Type: BIOLOGICAL

Varicella

Varicella Virus Vaccine Live; 0.5 mL, Subcutaneous

Intervention Type: BIOLOGICAL

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

Intervention Type: BIOLOGICAL

PCV13

Pneumococcal 13-valent Conjugate Vaccine; 0.5 mL, Intramuscular

Intervention Type: BIOLOGICAL

Eligibility Criteria

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.

• Minimum Eligible Age: 12 Months
• Maximum Eligible Age: 23 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Sanofi Pasteur, a Sanofi Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Sanofi Pasteur, a Sanofi Company

Locations

Acapulco, , Mexico

Mexico City, , Mexico

Tlaltizapán, , Mexico

Barnaul, , Russia

Kazan', , Russia

Krasnodar, , Russia

Moscow, , Russia

Murmansk, , Russia

Novosibirsk, , Russia

Perm, , Russia

Saint Petersburg, , Russia

Saint Petersburg, , Russia

Saint Petersburg, , Russia

Samara, , Russia

Smolensk, , Russia

Tomsk, , Russia

Yekaterinburg, , Russia

Ansan, , South Korea

Anyang, , South Korea

Daegu, , South Korea

Daejeon, , South Korea

Gwangju, , South Korea

Ilsan, , South Korea

Incheon, , South Korea

Jeju City, , South Korea

Seoul, , South Korea

Seoul, , South Korea

Seoul, , South Korea

Seoul, , South Korea

Seoul, , South Korea

Seoul, , South Korea

Seoul, , South Korea

Suwon, , South Korea

Wŏnju, , South Korea

Yangsan, , South Korea

Pathum Wan, Bangkok, Thailand

Rajthevi, Bangkok, Thailand

Countries

Mexico; Russia; South Korea; Thailand

References

Dhingra MS, Namazova-Baranova L, Arredondo-Garcia JL, Kim KH, Limkittikul K, Jantarabenjakul W, Perminova O, Kobashi IAR, Bae CW, Ojeda J, Park J, Chansinghakul D, B'Chir S, Neveu D, Bonaparte M, Jordanov E. Immunogenicity and safety of a quadrivalent meningococcal tetanus toxoid-conjugate vaccine administered concomitantly with other paediatric vaccines in toddlers: a phase III randomised study. Epidemiol Infect. 2021 Apr 5;149:e90. doi: 10.1017/S0950268821000698.

Reference Type: DERIVED

PMID: 33814028 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://www.sanofipasteur.com

Related info

Other Identifiers

U1111-1161-2787

Identifier Type: OTHER

Identifier Source: secondary_id

MET57

Identifier Type: -

Identifier Source: org_study_id