Trial Outcomes & Findings for Safety of a Quadrivalent Meningococcal Conjugate Vaccine Administered Concomitantly With Routine Pediatric Vaccines in Healthy Infants and Toddlers (NCT NCT03673462)

Last Updated: 2023-12-14

Results Overview

An AE was any untoward medical occurrence in a clinical investigation participant administered a medicinal product and which did not have any causal relationship with the treatment. An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the case report book (CRB) in terms of diagnosis and/or onset window post-vaccination. Immediate adverse events are unsolicited systemic adverse events occurring in the 30 minutes after injection. Reported AEs for each arm were presented as pre-specified in protocol.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

2797 participants

Primary outcome timeframe

Within 30 minutes post-any vaccination

Results posted on

2023-12-14

Participant Flow

Study was conducted at 75 sites in Puerto Rico and United States from 17 September 2018 to 16 March 2023.

A total of 2797 participants were enrolled and randomized in the study.

Participant milestones

Participant milestones
Measure	Group 1: MenACYW Conjugate Vaccine Healthy infants aged greater than equal to (\>=) 42 to less than equal to (\<=) 89 days (at the time of enrollment) received MenACYW Conjugate Vaccine at the age of Months 2, 4, 6, and 12 along with Pentacel® (DTaP-IPV/Hib vaccine) at 2, 4, and 6 months of age; PREVNAR 13® (pneumococcal 13-valent conjugate vaccine; PCV13) at 2, 4, 6, and 12 months of age; RotaTeq® (rotavirus vaccine) at 2, 4, and 6 months of age; ENGERIX-B® (hepatitis B vaccine) at 2 and 6 months of age; and M-M-R® II (measles, mumps, and rubella vaccine) and VARIVAX® (varicella vaccine) at 12 months of age.	Group 2: MENVEO® Healthy infants aged \>= 42 to \<= 89 days (at the time of enrollment) received MENVEO® Conjugate Vaccine at the age of Months 2, 4, 6, and 12 along with Pentacel® (DTaP-IPV/Hib vaccine) at 2, 4, and 6 months of age; PREVNAR 13® (PCV13) at 2, 4, 6, and 12 months of age; RotaTeq® (rotavirus vaccine) at 2, 4, and 6 months of age; ENGERIX-B® (hepatitis B vaccine) at 2 and 6 months of age; and M-M-R® II (measles, mumps, and rubella vaccine) and VARIVAX® (varicella vaccine) at 12 months of age.
Overall Study STARTED	2099	698
Overall Study Safety Analysis Set (SafAS)	2080	697
Overall Study Vaccinated at 2 Months	2080	695
Overall Study Vaccinated at 4 Months	2005	663
Overall Study Vaccinated at 6 Months	1951	648
Overall Study Vaccinated at 12 Months	1838	623
Overall Study COMPLETED	1799	611
Overall Study NOT COMPLETED	300	87

Reasons for withdrawal

Reasons for withdrawal
Measure	Group 1: MenACYW Conjugate Vaccine Healthy infants aged greater than equal to (\>=) 42 to less than equal to (\<=) 89 days (at the time of enrollment) received MenACYW Conjugate Vaccine at the age of Months 2, 4, 6, and 12 along with Pentacel® (DTaP-IPV/Hib vaccine) at 2, 4, and 6 months of age; PREVNAR 13® (pneumococcal 13-valent conjugate vaccine; PCV13) at 2, 4, 6, and 12 months of age; RotaTeq® (rotavirus vaccine) at 2, 4, and 6 months of age; ENGERIX-B® (hepatitis B vaccine) at 2 and 6 months of age; and M-M-R® II (measles, mumps, and rubella vaccine) and VARIVAX® (varicella vaccine) at 12 months of age.	Group 2: MENVEO® Healthy infants aged \>= 42 to \<= 89 days (at the time of enrollment) received MENVEO® Conjugate Vaccine at the age of Months 2, 4, 6, and 12 along with Pentacel® (DTaP-IPV/Hib vaccine) at 2, 4, and 6 months of age; PREVNAR 13® (PCV13) at 2, 4, 6, and 12 months of age; RotaTeq® (rotavirus vaccine) at 2, 4, and 6 months of age; ENGERIX-B® (hepatitis B vaccine) at 2 and 6 months of age; and M-M-R® II (measles, mumps, and rubella vaccine) and VARIVAX® (varicella vaccine) at 12 months of age.
Overall Study Adverse Event	11	1
Overall Study Protocol Violation	25	11
Overall Study Withdrawal by Parent/Guardian	162	56
Overall Study Lost to Follow-up	102	19

Baseline Characteristics

Safety of a Quadrivalent Meningococcal Conjugate Vaccine Administered Concomitantly With Routine Pediatric Vaccines in Healthy Infants and Toddlers

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group 1: MenACYW Conjugate Vaccine n=2099 Participants Healthy infants aged \>= 42 to \<= 89 days (at the time of enrollment) received MenACYW Conjugate Vaccine at the age of Months 2, 4, 6, and 12 along with Pentacel® (DTaP-IPV/Hib vaccine) at 2, 4, and 6 months of age; PREVNAR 13® (pneumococcal 13-valent conjugate vaccine; PCV13) at 2, 4, 6, and 12 months of age; RotaTeq® (rotavirus vaccine) at 2, 4, and 6 months of age; ENGERIX-B® (hepatitis B vaccine) at 2 and 6 months of age; and M-M-R® II (measles, mumps, and rubella vaccine) and VARIVAX® (varicella vaccine) at 12 months of age.	Group 2 MENVEO® n=698 Participants Healthy infants aged \>= 42 to \<= 89 days (at the time of enrollment) received MENVEO® Conjugate Vaccine at the age of Months 2, 4, 6, and 12 along with Pentacel® (DTaP-IPV/Hib vaccine) at 2, 4, and 6 months of age; PREVNAR 13® (PCV13) at 2, 4, 6, and 12 months of age; RotaTeq® (rotavirus vaccine) at 2, 4, and 6 months of age; ENGERIX-B® (hepatitis B vaccine) at 2 and 6 months of age; and M-M-R® II (measles, mumps, and rubella vaccine) and VARIVAX® (varicella vaccine) at 12 months of age.	Total n=2797 Participants Total of all reporting groups
Age, Continuous	64.7 days STANDARD_DEVIATION 6.63 • n=5 Participants	64.9 days STANDARD_DEVIATION 6.77 • n=7 Participants	64.7 days STANDARD_DEVIATION 6.67 • n=5 Participants
Sex: Female, Male Female	998 Participants n=5 Participants	336 Participants n=7 Participants	1334 Participants n=5 Participants
Sex: Female, Male Male	1101 Participants n=5 Participants	362 Participants n=7 Participants	1463 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	8 Participants n=5 Participants	0 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) Asian	28 Participants n=5 Participants	12 Participants n=7 Participants	40 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	10 Participants n=5 Participants	5 Participants n=7 Participants	15 Participants n=5 Participants
Race (NIH/OMB) Black or African American	210 Participants n=5 Participants	67 Participants n=7 Participants	277 Participants n=5 Participants
Race (NIH/OMB) White	1719 Participants n=5 Participants	580 Participants n=7 Participants	2299 Participants n=5 Participants
Race (NIH/OMB) More than one race	102 Participants n=5 Participants	31 Participants n=7 Participants	133 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	22 Participants n=5 Participants	3 Participants n=7 Participants	25 Participants n=5 Participants

PRIMARY outcome

Timeframe: Within 30 minutes post-any vaccination

Population: Analysis was performed on SafAS that included all participants who had received at least one dose of the study vaccines and had any safety data available.

Outcome measures

Outcome measures
Measure	Group 1: MenACYW Conjugate Vaccine n=2080 Participants Healthy infants aged \>= 42 to \<= 89 days (at the time of enrollment) received MenACYW Conjugate Vaccine at the age of Months 2, 4, 6, and 12 along with Pentacel® (DTaP-IPV/Hib vaccine) at 2, 4, and 6 months of age; PREVNAR 13® (pneumococcal 13-valent conjugate vaccine; PCV13) at 2, 4, 6, and 12 months of age; RotaTeq® (rotavirus vaccine) at 2, 4, and 6 months of age; ENGERIX-B® (hepatitis B vaccine) at 2 and 6 months of age; and M-M-R® II (measles, mumps, and rubella vaccine) and VARIVAX® (varicella vaccine) at 12 months of age.	Group 2: MENVEO® n=697 Participants Healthy infants aged \>= 42 to \<= 89 days (at the time of enrollment) received MENVEO® Conjugate Vaccine at the age of Months 2, 4, 6, and 12 along with Pentacel® (DTaP-IPV/Hib vaccine) at 2, 4, and 6 months of age; PREVNAR 13® (PCV13) at 2, 4, 6, and 12 months of age; RotaTeq® (rotavirus vaccine) at 2, 4, and 6 months of age; ENGERIX-B® (hepatitis B vaccine) at 2 and 6 months of age; and M-M-R® II (measles, mumps, and rubella vaccine) and VARIVAX® (varicella vaccine) at 12 months of age.
Number of Participants With Immediate Unsolicited Systemic Adverse Events (AEs)	7 Participants	2 Participants

PRIMARY outcome

Timeframe: Within 7 days post any vaccination

Population: Analysis was performed on SafAS. Here, 'Overall number of participants analyzed' = participants with available data for this outcome measure and 'Number analyzed' = participants with available data for each specified category.

A solicited reaction was an "expected" adverse reaction (AR) (sign or symptom) observed and reported under the conditions (nature and onset) pre-listed in the protocol and CRB and considered as related to the product administered. Solicited injection site reactions included Injection site tenderness, Injection site erythema, and Injection site swelling and were planned to be collected and reported for each vaccine separately; and not planned to be collected for Rotavirus vaccine as the vaccine was administered orally, and no injection site reactions were expected to occur. Reported AEs for each arm were presented as pre-specified in protocol.

Outcome measures

Outcome measures
Measure	Group 1: MenACYW Conjugate Vaccine n=2021 Participants Healthy infants aged \>= 42 to \<= 89 days (at the time of enrollment) received MenACYW Conjugate Vaccine at the age of Months 2, 4, 6, and 12 along with Pentacel® (DTaP-IPV/Hib vaccine) at 2, 4, and 6 months of age; PREVNAR 13® (pneumococcal 13-valent conjugate vaccine; PCV13) at 2, 4, 6, and 12 months of age; RotaTeq® (rotavirus vaccine) at 2, 4, and 6 months of age; ENGERIX-B® (hepatitis B vaccine) at 2 and 6 months of age; and M-M-R® II (measles, mumps, and rubella vaccine) and VARIVAX® (varicella vaccine) at 12 months of age.	Group 2: MENVEO® n=676 Participants Healthy infants aged \>= 42 to \<= 89 days (at the time of enrollment) received MENVEO® Conjugate Vaccine at the age of Months 2, 4, 6, and 12 along with Pentacel® (DTaP-IPV/Hib vaccine) at 2, 4, and 6 months of age; PREVNAR 13® (PCV13) at 2, 4, 6, and 12 months of age; RotaTeq® (rotavirus vaccine) at 2, 4, and 6 months of age; ENGERIX-B® (hepatitis B vaccine) at 2 and 6 months of age; and M-M-R® II (measles, mumps, and rubella vaccine) and VARIVAX® (varicella vaccine) at 12 months of age.
Number of Participants With Solicited Injection Site Reactions MenACYW or MENVEO: Injection site Tenderness	1501 Participants	499 Participants
Number of Participants With Solicited Injection Site Reactions MenACYW or MENVEO: Injection site Erythema	826 Participants	257 Participants
Number of Participants With Solicited Injection Site Reactions MenACYW or MENVEO: Injection site Swelling	557 Participants	170 Participants
Number of Participants With Solicited Injection Site Reactions PENTACEL: Injection site Tenderness	1388 Participants	456 Participants
Number of Participants With Solicited Injection Site Reactions PENTACEL: Injection site Erythema	770 Participants	255 Participants
Number of Participants With Solicited Injection Site Reactions PENTACEL: Injection site Swelling	562 Participants	178 Participants
Number of Participants With Solicited Injection Site Reactions PREVNAR 13: Injection site Tenderness	1464 Participants	496 Participants
Number of Participants With Solicited Injection Site Reactions PREVNAR 13: Injection site Erythema	889 Participants	298 Participants
Number of Participants With Solicited Injection Site Reactions PREVNAR 13: Injection site Swelling	656 Participants	206 Participants
Number of Participants With Solicited Injection Site Reactions ENGERIX-B: Injection site Tenderness	1199 Participants	395 Participants
Number of Participants With Solicited Injection Site Reactions ENGERIX-B: Injection site Erythema	539 Participants	192 Participants
Number of Participants With Solicited Injection Site Reactions ENGERIX-B: Injection site Swelling	347 Participants	115 Participants
Number of Participants With Solicited Injection Site Reactions M-M-R II: Injection site Tenderness	786 Participants	268 Participants
Number of Participants With Solicited Injection Site Reactions M-M-R II: Injection site Erythema	409 Participants	130 Participants
Number of Participants With Solicited Injection Site Reactions M-M-R II: Injection site Swelling	221 Participants	71 Participants
Number of Participants With Solicited Injection Site Reactions VARIVAX: Injection site Tenderness	724 Participants	252 Participants
Number of Participants With Solicited Injection Site Reactions VARIVAX: Injection site Erythema	364 Participants	129 Participants
Number of Participants With Solicited Injection Site Reactions VARIVAX: Injection site Swelling	208 Participants	70 Participants

PRIMARY outcome

Timeframe: Within 7 days post-any vaccination

A solicited reaction was an "expected" AR (sign or symptom) observed and reported under the conditions (nature and onset) pre-listed in the protocol and CRB and considered as related to the product administered. Solicited systemic reactions included fever, vomiting, crying abnormal, drowsiness, appetite loss, and irritability. Reported AEs for each arm were presented as pre-specified in protocol.

Outcome measures

Outcome measures
Measure	Group 1: MenACYW Conjugate Vaccine n=2019 Participants Healthy infants aged \>= 42 to \<= 89 days (at the time of enrollment) received MenACYW Conjugate Vaccine at the age of Months 2, 4, 6, and 12 along with Pentacel® (DTaP-IPV/Hib vaccine) at 2, 4, and 6 months of age; PREVNAR 13® (pneumococcal 13-valent conjugate vaccine; PCV13) at 2, 4, 6, and 12 months of age; RotaTeq® (rotavirus vaccine) at 2, 4, and 6 months of age; ENGERIX-B® (hepatitis B vaccine) at 2 and 6 months of age; and M-M-R® II (measles, mumps, and rubella vaccine) and VARIVAX® (varicella vaccine) at 12 months of age.	Group 2: MENVEO® n=676 Participants Healthy infants aged \>= 42 to \<= 89 days (at the time of enrollment) received MENVEO® Conjugate Vaccine at the age of Months 2, 4, 6, and 12 along with Pentacel® (DTaP-IPV/Hib vaccine) at 2, 4, and 6 months of age; PREVNAR 13® (PCV13) at 2, 4, 6, and 12 months of age; RotaTeq® (rotavirus vaccine) at 2, 4, and 6 months of age; ENGERIX-B® (hepatitis B vaccine) at 2 and 6 months of age; and M-M-R® II (measles, mumps, and rubella vaccine) and VARIVAX® (varicella vaccine) at 12 months of age.
Number of Participants With Solicited Systemic Reactions Fever	724 Participants	219 Participants
Number of Participants With Solicited Systemic Reactions Vomiting	542 Participants	163 Participants
Number of Participants With Solicited Systemic Reactions Crying abnormal	1437 Participants	478 Participants
Number of Participants With Solicited Systemic Reactions Drowsiness	1430 Participants	475 Participants
Number of Participants With Solicited Systemic Reactions Appetite lost	1015 Participants	350 Participants
Number of Participants With Solicited Systemic Reactions Irritability	1604 Participants	536 Participants

PRIMARY outcome

Timeframe: Within 30 days post any vaccination

Population: Analysis was performed on SafAS.

An AE was any untoward medical occurrence in a clinical investigation participant administered a medicinal product, and which does not necessarily have a causal relationship with this treatment. An unsolicited AE was an observed AE that does not fulfill the conditions prelisted in the CRB in terms of diagnosis and/or onset window post-vaccination. Unsolicited AEs includes both serious adverse events (SAEs) and non-serious unsolicited AEs. Reported AEs for each arm were presented as pre-specified in protocol.

Outcome measures

Outcome measures
Measure	Group 1: MenACYW Conjugate Vaccine n=2080 Participants Healthy infants aged \>= 42 to \<= 89 days (at the time of enrollment) received MenACYW Conjugate Vaccine at the age of Months 2, 4, 6, and 12 along with Pentacel® (DTaP-IPV/Hib vaccine) at 2, 4, and 6 months of age; PREVNAR 13® (pneumococcal 13-valent conjugate vaccine; PCV13) at 2, 4, 6, and 12 months of age; RotaTeq® (rotavirus vaccine) at 2, 4, and 6 months of age; ENGERIX-B® (hepatitis B vaccine) at 2 and 6 months of age; and M-M-R® II (measles, mumps, and rubella vaccine) and VARIVAX® (varicella vaccine) at 12 months of age.	Group 2: MENVEO® n=697 Participants Healthy infants aged \>= 42 to \<= 89 days (at the time of enrollment) received MENVEO® Conjugate Vaccine at the age of Months 2, 4, 6, and 12 along with Pentacel® (DTaP-IPV/Hib vaccine) at 2, 4, and 6 months of age; PREVNAR 13® (PCV13) at 2, 4, 6, and 12 months of age; RotaTeq® (rotavirus vaccine) at 2, 4, and 6 months of age; ENGERIX-B® (hepatitis B vaccine) at 2 and 6 months of age; and M-M-R® II (measles, mumps, and rubella vaccine) and VARIVAX® (varicella vaccine) at 12 months of age.
Number of Participants With Unsolicited Adverse Events	1352 Participants	437 Participants

PRIMARY outcome

Timeframe: From day of first vaccination (i.e., at the age of 2 months) up to 6 months after last vaccination (i.e., up to the age of 18 months)

Population: Analysis was performed on SafAS.

A SAE was any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. An AESI (serious or non-serious) was defined as one of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and rapid communication by the Investigator to the Sponsor was appropriate. Reported AEs for each arm were presented as pre-specified in protocol.

Outcome measures

Outcome measures
Measure	Group 1: MenACYW Conjugate Vaccine n=2080 Participants Healthy infants aged \>= 42 to \<= 89 days (at the time of enrollment) received MenACYW Conjugate Vaccine at the age of Months 2, 4, 6, and 12 along with Pentacel® (DTaP-IPV/Hib vaccine) at 2, 4, and 6 months of age; PREVNAR 13® (pneumococcal 13-valent conjugate vaccine; PCV13) at 2, 4, 6, and 12 months of age; RotaTeq® (rotavirus vaccine) at 2, 4, and 6 months of age; ENGERIX-B® (hepatitis B vaccine) at 2 and 6 months of age; and M-M-R® II (measles, mumps, and rubella vaccine) and VARIVAX® (varicella vaccine) at 12 months of age.	Group 2: MENVEO® n=697 Participants Healthy infants aged \>= 42 to \<= 89 days (at the time of enrollment) received MENVEO® Conjugate Vaccine at the age of Months 2, 4, 6, and 12 along with Pentacel® (DTaP-IPV/Hib vaccine) at 2, 4, and 6 months of age; PREVNAR 13® (PCV13) at 2, 4, 6, and 12 months of age; RotaTeq® (rotavirus vaccine) at 2, 4, and 6 months of age; ENGERIX-B® (hepatitis B vaccine) at 2 and 6 months of age; and M-M-R® II (measles, mumps, and rubella vaccine) and VARIVAX® (varicella vaccine) at 12 months of age.
Number of Participants With Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESIs) SAE	108 Participants	21 Participants
Number of Participants With Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESIs) AESI	19 Participants	1 Participants

PRIMARY outcome

Timeframe: From day of first vaccination (i.e., at the age of 2 months) up to 6 months after last vaccination (i.e., up to the age of 18 months)

Population: Analysis was performed on SafAS.

A MAAE was defined as a new onset of a condition that prompts the participant or participant's parent/guardian to seek unplanned medical advice at a health care provider's office or Emergency Department. Reported AEs for each arm were presented as pre-specified in protocol.

Outcome measures

Outcome measures
Measure	Group 1: MenACYW Conjugate Vaccine n=2080 Participants Healthy infants aged \>= 42 to \<= 89 days (at the time of enrollment) received MenACYW Conjugate Vaccine at the age of Months 2, 4, 6, and 12 along with Pentacel® (DTaP-IPV/Hib vaccine) at 2, 4, and 6 months of age; PREVNAR 13® (pneumococcal 13-valent conjugate vaccine; PCV13) at 2, 4, 6, and 12 months of age; RotaTeq® (rotavirus vaccine) at 2, 4, and 6 months of age; ENGERIX-B® (hepatitis B vaccine) at 2 and 6 months of age; and M-M-R® II (measles, mumps, and rubella vaccine) and VARIVAX® (varicella vaccine) at 12 months of age.	Group 2: MENVEO® n=697 Participants Healthy infants aged \>= 42 to \<= 89 days (at the time of enrollment) received MENVEO® Conjugate Vaccine at the age of Months 2, 4, 6, and 12 along with Pentacel® (DTaP-IPV/Hib vaccine) at 2, 4, and 6 months of age; PREVNAR 13® (PCV13) at 2, 4, 6, and 12 months of age; RotaTeq® (rotavirus vaccine) at 2, 4, and 6 months of age; ENGERIX-B® (hepatitis B vaccine) at 2 and 6 months of age; and M-M-R® II (measles, mumps, and rubella vaccine) and VARIVAX® (varicella vaccine) at 12 months of age.
Number of Participants With Medically Attended Adverse Event (MAAEs)	1581 Participants	526 Participants

Adverse Events

Group 1: MenACYW Conjugate Vaccine

Serious events: 108 serious events

Other events: 1889 other events

Deaths: 3 deaths

Group 2: MENVEO®

Serious events: 21 serious events

Other events: 642 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Trial Transparency Team

Sanofi Pasteur

Phone: 800-633-1610

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor must have the opportunity to review at least 60 days prior to submission for publication or presentation. If review indicates that potentially patentable participant matter would be disclosed, publication or public disclosure may be delayed for a maximum of an additional 60 days to allow for filing the necessary patent applications.
Publication restrictions are in place

Restriction type: OTHER