PENTACEL Rx

Immune responses to Pentacel were evaluated in four US studies: Studies 494-01, P3T06, 494-03, and M5A10. In Study M5A10, participants were randomly assigned to receive Pentacel or separately administered Daptacel, IPOL, and ActHIB at 2, 4, and 6 months of age. Pentacel or Control vaccines were concomitantly administered with 7-valent pneumococcal conjugate (PCV7, Wyeth Pharmaceuticals Inc.) at 2, 4, and 6 months of age, and Hepatitis B vaccine (Merck and Co. or GlaxoSmithKline Biologicals) at 2 and 6 months of age. 

Diphtheria and Tetanus

• The proportions of participants achieving diphtheria antitoxin and tetanus antitoxoid seroprotective levels 1 month following three and four doses of Pentacel or Daptacel (+ IPOL + ActHIB) in Study P3T06 were as followed, respectively:

• Post-Dose 3

• Diphtheria Antitoxin (% ≥0.01 IU/mL): 100% for Pentacel vs 100% for Daptacel

• Tetanus Antitoxoid (% ≥0.10 IU/mL): 99.7% for Pentacel vs 100% for Daptacel

• Post-Dose 4

• Diphtheria Antitoxin (% ≥0.10 IU/mL): 100% for Pentacel vs 100% for Daptacel

• Tetanus Antitoxoid (% ≥0.10 IU/mL): 100% for Pentacel vs 100% for Daptacel

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.

• 2587 infants received Daptacel and 2574 infants received a non-US licensed DT vaccine as placebo at 2, 4, and 6 months of age. 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.

• Serology Bridging Analysis

• Immune responses to FHA, PRN, and FIM in a subset of infants who received 3 doses of Daptacel in the Sweden I Efficacy Trial were compared to the Post-Dose 3 and Post-Dose 4 responses in a subset of US children from Study 494-01 who received Pentacel.

• The noninferiority criteria were met for seroconversion rates for anti-FHA and anti-FIM after Dose 4 of Pentacel compared to Dose 3 of Daptacel. The noninferiority criteria was not met for seroconversion for anti-PRN.

• The noninferiority criteria were met for GMCs for anti-FHA, anti-PRN, and anti-FIM after Dose 4 of Pentacel compared to Dose 3 of Daptacel. 

• Study P3T06

• US infants were randomly asigned to receive either Pentacel or Daptacel + IPOL + ActHIB at 2, 4, 6, and 15–16 months of age.

• The noninferiority criteria were met for seroconversion rates and GMCs for each of the pertussis antigens after Dose 3 of Pentacel compared with Dose 3 of Daptacel. 

• The noninferiority criteria were met for all comparisons after Dose 4 of Pentacel compared with Dose 4 of Daptacel, except for anti-PRN GMCs.

• Study 006

• US infants were randomly assigned to receive 3 doses of Vaxelis at 2, 4, and 6 months of age and Pentacel at 15 months of age, or control group vaccines (4 doses of Pentacel + Recombivax HB). All patients received concomitant Prevnar 13 at 2, 4, 6, and 15 months of age.

• The noninferiority criteria for antibody vaccine response rates and GMCs for all pertussis antigens were met after the 4th dose except for GMCs for PRN.

Poliomyelitis

• Study P3T06

• Infants were randomly assigned to receive the first 3 doses of Pentacel or Daptacel + IPOL + ActHIB at 2, 4, and 6 months of age, one month after the third dose of study vaccines.

• More than 99.4% of patients in both groups achieved neutralizing antibody levels of ≥1:8 for Poliovirus types 1, 2, and 3.

• Study 494-01

• Infants were randomly assigned to receive Pentacel or HCPDT + POLIOVAX + ActHIB.

• GMTs of antibodies to Poliovirus types 1, 2, and 3 one month after Dose 4 of Pentacel were 2304, 4178, and 4415, respectively, and one month following Dose 4 of POLIOVAX were 2330, 2840, and 3300, respectively.

Invasive Disease due to H. Influenzae Type b

• Study 494-01

• Pentacel did not meet the noninferiority criteria for the proportion of patients who achieved an anti-PRP level ≥1.0 mcg/mL and for anti-PRP GMCs compared with separately administered ActHIB.

• Studies P3T06 and M5A10

• Pentacel met the noninferiority criteria for the proportion of patient who achieved an anti-PRP level ≥1.0 mcg/mL compared with separately administered ActHIB.

• Study M5A10

• Pentacel met the noninferiority criteria for anti-PRP GMCs compared with separately administered ActHIB.

• Study 494-01

• At 15 months of age before receiving Dose 4 of study vaccines, 68.6% of Pentacel recipients (N = 829) and 80.8% of separately administered ActHIB recipients (N = 276) had an anti-PRP level ≥0.15 mcg/mL.

• After Dose 4, 98.2% of Pentacel recipients (N = 874) and 99.0% of separately administered ActHIB recipients (N = 291) had an anti-PRP level ≥1.0 mcg/mL. 

• Study P3T06

• At 15 months of age before receiving Dose 4 of study vaccines, 65.4% of Pentacel recipients (N = 335) and 60.7% of separately administered ActHIB recipients (N = 323) had an anti-PRP level ≥0.15 mcg/mL. 

• Following Dose 4 of study vaccines, 97.8% of Pentacel recipients (N = 361) and 95.9% of separately administered ActHIB recipients (N = 340) had an anti-PRP level ≥1.0 mcg/mL.