DAPTACEL Rx

Diphtheria

• A US study evaluated children who received 4 doses of Daptacel at 2, 4, 6 and 15 to 17 months of age. 

• After the third dose, 100% (N=1099) achieved diphtheria antitoxin levels of ≥0.01 IU/mL and 98.5% achieved diphtheria antitoxin levels of ≥0.10 IU/mL.

• Among a random subset of children who received the fourth dose of Daptacel at 15-16 months of age, 96.5% (N = 659) achieved diphtheria antitoxin levels of ≥1.0 IU/mL after the fourth dose. 

Tetanus

• A US study evaluated children who received 4 doses of Daptacel at 2, 4, 6 and 15 to 17 months of age.

• After the third dose, 100% (N = 1,037) achieved tetanus antitoxin levels of ≥0.10 IU/mL. 

• Among a random subset of children who received the fourth dose of Daptacel at 15-16 months of age, 98.8% (N = 681) achieved tetanus antitoxin levels of ≥1.0 IU/mL after the fourth dose. 

Pertussis

Sweden I Efficacy Trial

• A randomized, double-blinded, placebo-controlled study was conducted in Sweden during 1992-1995 (Sweden I Efficacy Trial) under the sponsorship of the National Institute of Allergy and Infectious Diseases.

• The study evaluated the efficacy and safety of Daptacel in 9829 infants who received 1 of 4 vaccines at 2, 4, and 6 months of age: Daptacel (N=2587); another investigational acellular pertussis vaccine (N=2566); whole-cell pertussis DTP vaccine (N=2102); or DT vaccine as placebo (Swedish National Bacteriological Laboratory; N =2574). The mean length of follow-up was 2 years after the third dose of vaccine.

• The protective efficacy of Daptacel was 84.9% (95% CI, 80.1-88.6) against pertussis after 3 doses using the WHO case definition (≥21 consecutive days of paroxysmal cough with culture or serologic confirmation or epidemiologic link to a confirmed case).

• The protective efficacy of Daptacel was 77.9% (95% CI, 72.6-82.2) against mild pertussis (≥1 day of cough with laboratory confirmation).

• Daptacel demonstrated to sustain protection against pertussis for the 2-year follow-up period.

US Bridging Study

• The study compared the antibody responses following 3 doses of Daptacel in US infants at 2, 4, and 6 months of age to those from a subset of the infants enrolled in the Sweden I Efficacy Trial. The study evaluated 2 lots of Daptacel, including the lot used in the Sweden I Efficacy Trial. Assays were performed in parallel on the available sera from the US and Swedish infants.

• Antibody responses to all the antigens were similar except for those to the PRN component. For both lots of Daptacel, the geometric mean concentration (GMC) and percent response to PRN in US infants (Lot 006, N = 107; Lot 009, N = 108) were significantly lower after 3 doses of vaccine than in Swedish infants (N = 83).

• In separate US and Canadian studies in which children received Daptacel at 2, 4 and 6 months of age, with a fourth dose at either 17-20 months (Canadian study) or 15-16 months (random subset from US study) of age, antibody responses to each pertussis antigen following the fourth dose (Canadian study N = 275; US study N = 237-347) were at least as high as those seen in the Swedish infants after 3 doses.

US Study 005

• The study randomly assigned infants to receive 3 doses of Vaxelis at 2, 4, and 6 months of age and Daptacel and PedvaxHIB [Haemophilus b Conjugate Vaccine (Meningococcal Protein Conjugate)] at 15 months of age, or Control group vaccines (3 doses of Pentacel vaccine at 2, 4, and 6 months of age + Recombivax HB [Hepatitis B Vaccine (Recombinant)] at 2 and 6 months of age and Daptacel and ActHIB [Haemophilus b Conjugate Vaccine (Tetanus Toxoid Conjugate)] at 15 months of age). 

• All patients received concomitant Prevnar 13 at 2, 4, 6, and 15 months of age. To complete the 4-dose pertussis primary vaccination series, participants in both groups received Daptacel at 15 months of age and were evaluated for immune responses to pertussis antigens one month later.

• The non-inferiority criteria for vaccine response rates and GMCs for all pertussis antigens were met following the fourth dose.

Concomitantly Administered Vaccines

US Bridging Study

• The study evaluated infants who received Daptacel concomitantly with Hib conjugate vaccine (Sanofi Pasteur SA) according to local practices. Anti-PRP immune response was 261 infants who received 3 doses of Hib conjugate vaccine.

• One month after the third dose, 96.9% achieved anti-PRP antibody levels of at least 0.15 mcg/mL and 82.7% achieved antibody levels of at least 1.0 mcg/mL. 

US Study

• The study evaluated infants who received Daptacel concomitantly with Hib conjugate vaccine, IPV, 7-valent pneumococcal conjugate vaccine, and hepatitis B vaccine at 7 months of age.

• 100% of patients (N=1050-1097) had protective neutralizing antibody levels (≥1:8 1/dil) for poliovirus types 1, 2 and 3; and 92.4% (N = 998) achieved anti-hepatitis B surface antigen levels ≥10.0 mIU/mL.

• 91.3%-98.9% (N = 1,027-1,029) achieved anti-pneumococcal polysaccharide levels ≥0.5 mcg/mL for serotypes 4, 9V, 14, 18C, 19F and 23F and 80.7% (N = 1,027) achieved an anti-pneumococcal polysaccharide level ≥0.5 mcg/mL for serotype 6B.

• The mumps seroresponse rate was lower when Daptacel was administered concomitantly (86.6%; N = 307) vs non-concomitantly (90.1%; N = 312) with the first dose of MMR vaccine [upper limit of 90% confidence interval for difference in rates (non-concomitant minus concomitant) >5%]. There was no evidence for interference in the immune response to the measles, rubella, and varicella antigens or to the fourth dose of the 7-valent pneumococcal conjugate vaccine with concomitant administration of Daptacel. 

US Randomized, Multicenter Clinical Trial

• The study evaluated children 4 to 6 years of age who received Daptacel concomitantly with: IPV (Sanofi Pasteur SA) followed 30 days later by Menactra (Group A); Menactra followed 30 days later by IPV (Group B); or 30 days after concomitant administration of Menactra and IPV (Group C). Sera were obtained approximately 30 days after each respective vaccination.

• Antibody response to PT, FHA and PRN (GMC), tetanus and diphtheria when Daptacel was administered with Group B were noninferior to those observed when Daptacel (and IPV) were administered with Group A.

• The anti-FIM GMCs were marginally lower when Daptacel and Menactra were administered concomitantly but the clinical significance is unknown.

• When Daptacel (and IPV) were administered 30 days prior to Menactra [Group A], significantly lower serum-bactericidal assay-human complement (SBA-H) GMTs to all 4 meningococcal serogroups were observed compared to when Menactra (and IPV) were administered 30 days prior to Daptacel [Group C]. 

• When Daptacel was administered concomitantly with Menactra [Group B], SBA-H GMTs to meningococcal serogroups A, C, and W-135 were non-inferior to those observed when Menactra (and IPV) were administered [Group C]. The non-inferiority criterion was marginally missed for meningococcal serogroup Y.