Primary Vaccination

• Individuals 2 years of age and older receive a single dose.

Booster Vaccination

• A single dose of MenQuadfi may be administered to individuals 13 years of age and older who are at continued risk for meningococcal disease if at least 3 years have elapsed since a prior dose of meningococcal (groups A, C, W, Y) conjugate vaccine.

Vaccination Following Prior Dose of Meningococcal Polysaccharide Vaccine

• A single dose of MenQuadfi may be administered if at least 3 years have elapsed since a prior dose of meningococcal polysaccharide vaccine.

Reduced Immune Response

Some individuals with altered immunocompetence, including some individuals receiving immunosuppressant therapy, may have reduced immune responses to MenQuadfi.

Complement Deficiency

Persons with certain complement deficiencies and persons receiving treatment that inhibits terminal complement activation (for example, eculizumab) are at increased risk for invasive disease caused by N. meningitidis, including invasive disease caused by serogroups A, C, W, and Y, even if they develop antibodies following vaccination with MenQuadfi [see Clinical Pharmacology (12.1)].

Safety Monitoring

Participants were monitored for immediate reactions for 30 minutes following vaccination while at the study site. Solicited injection site and systemic reactions were recorded by participants or by parents/guardians in a diary card at home daily for 7 days following vaccination. All unsolicited adverse events that occurred within 30 days following vaccination were recorded by participants or by parents/guardians and collected by the study site at the next visit. Unsolicited adverse events that were medically attended (i.e., visits to an emergency room, or an unexpected visit to a health care provider), and all serious adverse events (SAEs) were collected for at least 6 months after vaccination for all studies except Study 7 [NCT04142242], in which these safety data were collected for at least 1 month.

Primary Vaccination

Booster Vaccination Following Priming with a Meningococcal Conjugate Vaccine; Vaccination Following a Prior Dose of a Meningococcal Polysaccharide Vaccine

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to MenQuadfi during pregnancy. To enroll in or obtain information about the registry, call Sanofi Pasteur at 1-800-822-2463.

Risk Summary

All pregnancies have a risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

There are no clinical studies of MenQuadfi in pregnant women. Available human data on MenQuadfi administered to pregnant women are insufficient to inform vaccine-associated risks in pregnancy. A developmental toxicity study in female rabbits administered a full human dose (0.5 mL) prior to mating and during gestation period revealed no evidence of harm to the fetus due to MenQuadfi (see Animal Data).

Data

Risk Summary

It is not known whether MenQuadfi is excreted in human milk. Data are not available to assess the effects of MenQuadfi on the breastfed infant or on milk production/excretion.

The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for MenQuadfi and any potential adverse effects on the breastfed child from MenQuadfi or from the underlying maternal condition. For preventive vaccines, the underlying maternal condition is susceptibility to disease prevented by the vaccine.

Immunogenicity in Children 2 through 9 Years of Age

Immunogenicity of MenQuadfi compared to Menveo in participants 2 through 9 years of age was evaluated in Study 1 (NCT03077438). The hSBA seroresponse rate and GMTs are presented in Table 7.

Immune non-inferiority, based on seroresponse rates, was demonstrated for MenQuadfi as compared to Menveo for all four serogroups.

Immunogenicity in Adolescents 10 through 17 Years of Age

Immunogenicity of MenQuadfi compared to Menveo in participants 10 through 17 years of age was evaluated in Study 2 (NCT02199691). Study 2 was conducted in healthy meningococcal vaccine naïve participants and evaluated seroresponse rates following administration with either MenQuadfi alone, Menveo alone, MenQuadfi co-administered with Tdap, and HPV, or Tdap and HPV alone. The hSBA seroresponse rate and GMTs for Study 2 are presented in Table 8.

Immune non-inferiority, based on seroresponse, was demonstrated for MenQuadfi as compared to Menveo for all four serogroups.

Study 2 (NCT02199691) was conducted in healthy meningococcal vaccine naïve male and female participants and evaluated seroresponses following administration with either MenQuadfi alone; Menveo alone; MenQuadfi co-administered with Tdap, and HPV; or Tdap and HPV alone. The hSBA seroresponse rate and GMTs for the MenQuadfi alone and Menveo alone groups are presented in Table 8.

Study 3 evaluated the immunogenicity of MenQuadfi (N=1097-1098) compared to Menactra (N=300) in healthy meningococcal-naïve participants 10 through 17 years of age. Seroresponse rates for MenQuadfi were noninferior to those of Menactra for all serogroups based on the same non-inferiority criteria defined for Study 2.

Immunogenicity in Adults 18 through 55 Years of Age

Immunogenicity of MenQuadfi compared to Menactra in participants 18 through 55 years of age was evaluated in Study 3 (NCT02842853). The hSBA seroresponse rate and GMTs are presented in Table 9.

Immune non-inferiority, based on seroresponse rates, was demonstrated for MenQuadfi as compared to Menactra for all four serogroups.

Immunogenicity in Adults 56 Years of Age and Older

Immunogenicity of MenQuadfi compared to Menomune in participants 56 years and older was evaluated in Study 4 (NCT02842866).

Enrollment was stratified by age category: 56 through 64 years of age (44.3%), 65 through 74 years of age (39.7%), and 75 years of age and older (15.9%). The overall mean age of participants who received MenQuadfi was 66.9 years; range: 56 through 89.8 years of age. The mean age for participants in the 56 through 64 years age stratum who received MenQuadfi was 60.4 years, the mean age for participants ≥ 65 years age stratum who received MenQuadfi was 72.2 years.

The hSBA seroresponse rate and GMTs are presented in Table 10.

Immune non-inferiority, based on seroresponse rates, was demonstrated for MenQuadfi as compared to Menomune for all four serogroups.

Immunogenicity in Adolescents and Adults at least 15 Years of Age and Older

Immunogenicity of a booster dose of MenQuadfi compared to a booster dose of Menactra was evaluated in Study 5 (NCT02752906). The study-enrolled participants 15 years of age and older who had received a primary dose of Menveo or Menactra 4 to 10 years previously.

Immune non-inferiority, based on seroresponse rates, was demonstrated for MenQuadfi as compared to Menactra for all four serogroups.

For a description of study design and number of participants, see section 6.1 Booster Vaccination Following Priming with a Meningococcal Conjugate Vaccine; Vaccination Following a Prior Dose of a Meningococcal Polysaccharide Vaccine. The primary immunogenicity endpoint was hSBA seroresponse to each serogroup 30 days following booster vaccination with MenQuadfi or Menactra given to participants who received a prior dose of Menveo or Menactra 4 to 10 years ago. The other endpoints included the proportions of participants with post-vaccination hSBA ≥1:8 and the hSBA GMTs for each serogroup. These endpoints were also evaluated at 6 days post vaccination in a subset.

Seroresponse rates at Day 30 following booster vaccination with MenQuadfi were 92.2% for serogroup A, 97.1% for serogroup C, 98.2% for serogroup W, and 97.4% for serogroup Y, as compared to 87.1% for serogroup A, 91.8% for serogroup C, 90.7% for serogroup W, and 95.6% for serogroup Y, following booster vaccination with Menactra. At Day 6, following booster vaccination with MenQuadfi, seroresponse rates were 72.7%, 83.6%, 94.5%, and 90.9% for serogroups A, C, W, and Y, respectively.

The hSBA GMTs were 173, 334, 499, and 302 for serogroups A, C, W, and Y at Day 6, and 497, 2618, 1747, and 2070, respectively, for the 4 serogroups at Day 30 following booster dose of MenQuadfi.

Overall, similar seroresponse rates were observed for those participants who received booster vaccination with Menactra.

Immunogenicity in Adolescents and Adults 13 through 26 Years of Age

Immunogenicity of a booster dose of MenQuadfi was evaluated in Study 6 (NCT04084769). The study enrolled participants 13 through 26 years of age who had received a primary dose of MenQuadfi or Menveo 3–6 years previously in Study 2 or Study 3.

For a description of study design and number of participants, see section 6.1 Booster Vaccination Following Priming with a Meningococcal Conjugate Vaccine; Vaccination Following a Prior Dose of a Meningococcal Polysaccharide Vaccine. The primary immunogenicity endpoints were hSBA seroresponse to each serogroup 30 days following a booster vaccination with MenQuadfi given to participants who received a prior dose of MenQuadfi or Menveo 3–6 years previously (Table 11). The other endpoints included hSBA GMTs for each serogroup. These endpoints were also evaluated at 6 days post vaccination in a subset (Per-Protocol Analysis Set 1).

Seroresponse rates at Day 6 following booster dose with MenQuadfi were 82.6%, 89.1%, 97.8%, and 95.7% for serogroups A, C, W, and Y, respectively, in MenQuadfi-primed participants (N=46) and 77.8%, 93.3%, 88.9%, and 91.1% for serogroups A, C, W, and Y, respectively, in Menveo-primed participants (N=45).

Following a booster dose of MenQuadfi, the hSBA GMTs at Day 6 were 289, 3799, 1928, and 1658 for MenQuadfi-primed participants (N=46) and 161, 919, 708, and 800 for Menveo-primed participants (N=45) for serogroups A, C, W, and Y, respectively. At D30, the hSBA GMTs were 502, 3708, 2290, and 2308 for MenQuadfi-primed participants (N=174) and 399, 2533, 2574, and 3036 for Menveo-primed participants (N=176).

Prior to booster vaccination, the percentage of subjects with hSBA titers ≥1:8 for serogroups A, C, W, and Y were 71.3%, 87.9%, 86.2%, and 79.9% for those who received a prior dose of MenQuadfi 3-6 years earlier (N=174), and 71.0%, 50.6%, 77.8%, and 52.8% for those who received a prior dose of Menveo 3-6 years earlier (N=176).

Immunogenicity in Older Adults ≥ 59 Years of Age

Immunogenicity of a dose of MenQuadfi was evaluated in Study 7 (NCT04142242). The study enrolled participants ≥ 59 years of age who had received a prior dose of MenQuadfi or Menomune at least 3 years previously in Study 4 (NCT02842866).

For a description of study design and number of participants, see section 6.1 Booster Vaccination Following Priming with a Meningococcal Conjugate Vaccine; Vaccination Following a Prior Dose of a Meningococcal Polysaccharide Vaccine. The primary immunogenicity endpoint was hSBA seroresponse to each serogroup 30 days following vaccination with MenQuadfi in participants who had received a prior dose of Menomune 3 years previously. Additionally, hSBA seroresponse 30 days following vaccination with MenQuadfi in MenQuadfi-primed participants was also assessed (Table 12). The other endpoints included the hSBA GMTs for each serogroup. These endpoints were also evaluated at 6 days post vaccination in a subset (Per-Protocol Analysis Set 2).

Seroresponse rates at Day 6 following vaccination with MenQuadfi were 36.2%, 77.6%, 70.7%, and 72.4% for serogroups A, C, W, and Y, respectively, in MenQuadfi-primed participants (N=58) and 8.1%, 8.1%, 6.5%, and 8.1% for serogroups A, C, W, and Y, respectively, in participants who received a prior dose of Menomune (N=62). Following vaccination with MenQuadfi, the hSBA GMTs at Day 6 were 44, 206, 118, and 151 for MenQuadfi-primed participants (N=58) and 13, 11, 10, and 11 for participants who received a prior dose of Menomune (N=62) for serogroups A, C, W, and Y, respectively. At D30, the hSBA GMTs were 162, 638, 419, and 566 for MenQuadfi-primed participants (N=145) and 57, 56, 31, and 41 for participants who received a prior dose of Menomune (N=130).

Prior to MenQuadfi vaccination, the percentage of subjects with hSBA titers ≥1:8 for serogroups A, C, W, and Y were 64.8%, 73.8%, 66.9%, and 72.4% for those who received a prior dose of MenQuadfi at least 3 years earlier (N=145), and 65.4%, 49.2%, 40.0%, and 41.5% for those who received a prior dose of Menomune at least 3 years earlier (N=130).