Clinical trial NCT03205371: Immunogenicity and Safety of a Meningococcal Conjugate Vaccine Given Concomitantly With Other Vaccines in Toddlers
Official title: Immunogenicity and Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine Administered Concomitantly With Other Pediatric Vaccines in Healthy Toddlers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Meningitis, Meningococcal
Keywords: Meningitis
Meningococcal Meningitis
Meningococcal Infections
MenACYW Conjugate vaccine
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2017-07-02
Enrollment: 1183
Sex: ALL
Minimum age (years): 12
Maximum age (years): 23
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase III, open-label, randomized, parallel-group, active-controlled, multicenter study
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: 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
timeFrame: Day 0 and Day 30 post-vaccination
measure: 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
timeFrame: Day 0 and Day 30 post-vaccination
measure: 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
timeFrame: Day 0 up to Day 30 post-vaccination
measure: 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
timeFrame: Day 30 post-vaccination
Secondary outcomes:
measure: 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
timeFrame: Day 0 and Day 30 post-vaccination
measure: 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
timeFrame: Day 0 and Day 30 post-vaccination
measure: 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
timeFrame: Day 0 and Day 30 post-vaccination
measure: 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
timeFrame: Day 0 (for tetanus only) and Day 30 post-vaccination
measure: 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
timeFrame: Day 0 (tetanus only) and Day 30 post-vaccination
measure: 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
timeFrame: Day 0 and Day 30 post-vaccination
measure: 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
timeFrame: Day 0 and Day 30 post-vaccination
measure: Percentage of Participants With Immune Response Following Injection With PCV13 Vaccine Administered Alone or Concomitantly With the MenACYW Conjugate Vaccine: Groups 7 and 9
timeFrame: Day 0 and Day 30 post-vaccination
measure: Number of Participants Reporting at Least One Solicited Injection Site Reactions (Tenderness, Erythema, and Swelling): Groups 1, 2, 3, 10, 11, and 12
timeFrame: Within 7 days post vaccination
measure: Number of Participants Reporting at Least One Solicited Injection Site Reactions (Tenderness, Erythema, and Swelling): Groups 4, 5, and 6
timeFrame: Within 7 days post vaccination
measure: Number of Participants Reporting at Least One Solicited Injection Site Reactions (Tenderness, Erythema, and Swelling): Groups 7, 8, and 9
timeFrame: Within 7 days post vaccination
measure: Number of Participants Reporting at Least One Solicited Systemic Reactions (Fever, Vomiting, Abnormal Crying, Drowsiness, Appetite Loss, and Irritability)
timeFrame: Within 7 days post vaccination
Other outcomes:
Locations:
city: Ansan
country: Korea, Republic of
city: Anyang
country: Korea, Republic of
city: Daegu
country: Korea, Republic of
city: Daejeon
country: Korea, Republic of
city: Gwangju
country: Korea, Republic of
city: Ilsan
country: Korea, Republic of
city: Incheon
country: Korea, Republic of
city: Jeju City
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Suwon-si
country: Korea, Republic of
city: Wŏnju
country: Korea, Republic of
city: Yangsan
country: Korea, Republic of
city: Acapulco
country: Mexico
city: Mexico City
country: Mexico
city: Tlaltizapan
country: Mexico
city: Barnaul
country: Russian Federation
city: Kazan'
country: Russian Federation
city: Krasnodar
country: Russian Federation
city: Moscow
country: Russian Federation
city: Murmansk
country: Russian Federation
city: Novosibirsk
country: Russian Federation
city: Perm
country: Russian Federation
city: Saint Petersburg
country: Russian Federation
city: Saint Petersburg
country: Russian Federation
city: Saint Petersburg
country: Russian Federation
city: Samara
country: Russian Federation
city: Smolensk
country: Russian Federation
city: Tomsk
country: Russian Federation
city: Yekaterinburg
country: Russian Federation
city: Pathum Wan
country: Thailand
state: Bangkok
city: Rajthevi
country: Thailand
state: Bangkok
Study officials:
affiliation: Sanofi Pasteur, a Sanofi Company
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.