Immunogenicity and safety of a cell culture-based ... - Semantic Scholar

HUMAN VACCINES & IMMUNOTHERAPEUTICS 2016, VOL. 12, NO. 9, 2278–2288 http://dx.doi.org/10.1080/21645515.2016.1182270

RESEARCH PAPER

Immunogenicity and safety of a cell culture-based quadrivalent influenza vaccine in adults: A Phase III, double-blind, multicenter, randomized, non-inferiority study Stephan Barta, Kevin Cannonb, Darrell Herringtonc, Richard Millsd, Eduardo Forleo-Netoe, Kelly Linderte, and Ahmed Abdul Mateenf a Optimal Research LLC, Rockville, MD, USA; bPMG Research of Wilmington, Wilmington, NC, USA; cBenchmark Research, San Angelo, TX, USA; dPMG Research of Charleston, Mt. Pleasant, SC, USA; eNovartis Vaccines and Diagnostics Inc., Cambridge, MA, USA; fNovartis Pharmaceuticals Canada Inc., Dorval, Quebec, Canada

ABSTRACT

ARTICLE HISTORY

Quadrivalent influenza vaccines (QIVs), which include both B lineage strains, are expected to provide broader protection than trivalent influenza vaccines (TIVs). The non-inferiority, immunogenicity, and safety of a cell culture-based investigational QIVc and 2 TIVs (TIV1c, TIV2c), in adults (
18 y), were evaluated in this Phase III, double-blind, multicenter study. A total of 2680 age-stratified subjects were randomized (2:1:1) to receive 1 dose of QIVc (n D 1335), TIV1c (n D 676), or TIV2c (n D 669). TIV1c (B/Yamagata) and TIV2c (B/Victoria) differed only in B strain lineage. The primary objective was to demonstrate noninferiority of the hemagglutinin-inhibition antibody responses of QIVc against TIVc, 22 d post-vaccination. Secondary objectives included the evaluation of immunogenicity of QIVc and TIVc in younger (
18 – 1:40 B/Victoria GMTs GMR HI titers >1:40

HI
1:10

QIVc

TIV1c/TIV2c

QIVc

TIV1c/TIV2c

n D 187 208.6 (163.2–266.5) 40.7 (31.8–52.0) 87.2 (81.5–91.6) n D 81 98.2 (72.1–133.6) 19.6 (14.4–26.8) 84.0 (74.1–91.2) n D 75 68.4 (48.3–96.6) 13.7 (9.7–19.4) 70.7 (59.0–80.6) n D 37 78.5 (45.4–135.9) 15.7 (9.1–27.2) 78.4 (61.8–90.2)

n D 97 178.1 (125.0–253.7) 35.1 (24.6–50.1) 85.6 (77.0–91.9) n D 42 113.1 (74.0–173.0) 22.6 (14.8–34.6) 88.1 (74.4–96.0) n D 30 87.7 (52.1–147.7) 17.5 (10.4–29.5) 80.0 (61.4–92.3) n D 24 89.8 (48.9–165.0) 18.0 (9.8–33.0) 83.3 (62.6–95.3)

n D 1124 319.3 (297.6–342.7) 3.5 (3.3–3.8) 98.0 (96.9–98.7) n D 1172 407.7 (384.0–433.0) 2.7 (2.5–2.9) 99.4 (98.8–99.8) n D 1236 141.1 (133.1-149.7) 2.7 (2.5–2.9) 95.3 (94.0–96.4) n D 1215 181.4 (172.0–191.3) 2.8 (2.7–3.0) 98.2 (97.3–98.9)

n D 567 327.5 (297.1–361.0) 3.6 (3.3–4.0) 98.4 (97.0–99.3) n D 595 412.8 (378.2–450.0) 2.6 (2.4–2.8) 99.4 (98.4–99.8) n D 634 118.3 (109.0-128.3) 2.4 (2.2–2.6) 92.3 (89.9–94.2) n D 615 168.1 (155.4–181.7) 2.6 (2.4–2.8) 97.5 (95.9–98.6)

FAS D full analysis set; GMR, geometric mean ratio (day 22/day 1).

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Table 3. The superiority of HI antibody responses of QIVc to TIV1c and TIV2c over the unmatched B strain, at 3 wks (day 22) after vaccination in terms of the differences in percentages of subjects achieving seroconversion and the between group GMT ratios (FAS). QIVc n D 1311 B/Yamagata strain B/Victoria strain

177.1 (167.8–187.1) 135.4 (127.6–143.7)

TIV1c n D 664 GMTs (95% CI) – 91.7 (85.7–98.2)

TIV2c n D 657 76.3 (70.4–82.7) –

% seroconversion (95% CI) B/Yamagata strain B/Victoria strain

39.7 % (37.0–42.4) 36.6% (34.0–39.3)

– 17.2% (14.4–20.3)

Vaccine Group ratio 0.5 (0.5–0.5) 0.6 (0.6–0.7) Vaccine Group difference

18% (15.1–21.1) –

¡21.7% (¡25.5, ¡17.7%) ¡19.4% (¡23.2%, ¡15.5)

Bold D superiority criteria met. Superiority margin: the upper limit of the 2-sided 95% CIs for the ratio of GMTs (GMT TIV1c or TIV2c/GMT QIVc) for HI antibody should be