<abstract xmlns="http://www.w3.org/1999/xhtml"><sec id="j_abm-2018-0008_s_005_w2aab3b7b7b1b6b1aab1c17b1Aa"><h3>Background</h3><p>Human cases of highly pathogenic avian-origin influenza A/H5N1 infection continue to be reported to the World Health Organization, and recent outbreaks of human cases of other zoonotic influenza strains highlight the continued need for strategies to mitigate influenza pandemic potential.</p></sec><sec id="j_abm-2018-0008_s_006_w2aab3b7b7b1b6b1aab1c17b2Aa"><h3>Methods</h3><p>A Phase II–III randomized, placebo-controlled, observer-blind trial was conducted to assess the immunogenicity, reactogenicity, and safety of two 1.9 μg hemagglutinin doses of AS03<sub>B</sub>-adjuvanted H5N1 (AS03<sub>B</sub>-H5N1; A/Indonesia) vaccine in children (6 months to &lt;18 years old) of Thailand, the United States, and Canada (Year 1, published elsewhere). After database lock in Year 1, the trial was unblinded, and children who had been randomized to receive placebo and continued to fulfill the eligibility criteria were invited to participate in an open-label, one-way, crossover safety extension phase, in which they received AS03<sub>B</sub>-H5N1 vaccine. Here we report the safety analysis in Year 2.</p></sec><sec id="j_abm-2018-0008_s_007_w2aab3b7b7b1b6b1aab1c17b3Aa"><h3>Results</h3><p>A total of 155 children were vaccinated in Year 2. The most frequent solicited adverse event (AE) during 7 days post vaccination was injection site pain. Irritability or fussiness was reported in about one-third of younger children (aged &lt;6 years) during 7 days post vaccination and was the most common solicited general AE in this age group. Postvaccination temperature (≥38°C) was reported in 4 (5.1%) children. The most common solicited general AEs in older children (aged ≥6 years) were muscle aches, headache, and fatigue. The AS03<sub>B</sub>-H5N1 vaccine had a clinically acceptable safety profile up to 385 days post vaccination.</p></sec><sec id="j_abm-2018-0008_s_008_w2aab3b7b7b1b6b1aab1c17b4Aa"><h3>Conclusions</h3><p>Safety in the crossover phase was acceptable and consistent with that observed in vaccine recipients in the randomized, blinded phase of the study.</p></sec><sec id="j_abm-2018-0008_s_009_w2aab3b7b7b1b6b1aab1c17b5Aa"><h3>Clinical trial registration</h3><p>ClinicalTrials.gov: NCT01310413.</p></sec></abstract>

BackgroundHuman cases of highly pathogenic avian-origin influenza A/H5N1 infection continue to be reported to the World Health Organization, and recent outbreaks of human cases of other zoonotic influenza strains highlight the continued need for strategies to mitigate influenza pandemic potential.MethodsA Phase II–III randomized, placebo-controlled, observer-blind trial was conducted to assess the immunogenicity, reactogenicity, and safety of two 1.9 μg hemagglutinin doses of AS03B-adjuvanted H5N1 (AS03B-H5N1; A/Indonesia) vaccine in children (6 months to <18 years old) of Thailand, the United States, and Canada (Year 1, published elsewhere). After database lock in Year 1, the trial was unblinded, and children who had been randomized to receive placebo and continued to fulfill the eligibility criteria were invited to participate in an open-label, one-way, crossover safety extension phase, in which they received AS03B-H5N1 vaccine. Here we report the safety analysis in Year 2.ResultsA total of 155 children were vaccinated in Year 2. The most frequent solicited adverse event (AE) during 7 days post vaccination was injection site pain. Irritability or fussiness was reported in about one-third of younger children (aged <6 years) during 7 days post vaccination and was the most common solicited general AE in this age group. Postvaccination temperature (≥38°C) was reported in 4 (5.1%) children. The most common solicited general AEs in older children (aged ≥6 years) were muscle aches, headache, and fatigue. The AS03B-H5N1 vaccine had a clinically acceptable safety profile up to 385 days post vaccination.ConclusionsSafety in the crossover phase was acceptable and consistent with that observed in vaccine recipients in the randomized, blinded phase of the study.Clinical trial registrationClinicalTrials.gov: NCT01310413.

Reactogenicity and safety of AS03<sub>B</sub>-adjuvanted H5N1 influenza vaccine in children: an open-label, one-way, crossover trial

Asian Biomedicine

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Reactogenicity and safety of AS03-adjuvanted H5N1 influenza vaccine in children: an open-label, one-way, crossover trial

BackgroundHuman cases of highly pathogenic avian-origin influenza A/H5N1 infection continue to be reported to the World Health Organization, and recent...

AE type	TVC (N = 155)

	n	% (95% CI)
Days 0–42
≥1 AE(s)	41	26.5 (19.7, 34.1)
≥1 Grade 3 AE(s)	3	1.9 (0.4, 5.6)
≥1 AE(s) causally related to vaccination Causal relationship with vaccination based on the medical assessment by the investigator	3	1.9 (0.4, 5.6)
Days 0–385
≥1 MAE(s)	36	23.2 (16.8, 30.7)
≥1 SAE(s)	2	1.3 (0.2, 4.6)
≥1 pIMD	0	–

Solicited symptom				TVC Includes all children who received at least one dose of vaccine for whom diary cards of solicited events were available (N = 154)
		All events				Grade 3

	n			% (95% CI)	n			% (95% CI)

Injection site
Pain	111			72.1 (64.3, 79.0)	8			5.2 (2.3, 10.0)
Redness	6			3.9 (1.4, 8.3)	0			0.0 (0.0, 2.4)
Swelling	5			3.2 (1.1, 7.4)	0			0.0 (0.0, 2.4)

		<6 years (n = 79)				6–<18 years (n = 75)

	All events		Grade 3		All events		Grade 3

	n	% (95% CI)	n	% (95% CI)	n	% (95% CI)	n	% (95% CI)

General
Drowsiness	23	29.1 (19.4, 40.4)	1	1.3 (0.0, 6.9)	–		–
Irritability/fussiness	28	35.4 (25.0, 47.0)	1	1.3 (0.0, 6.9)	–		–
Loss of appetite	18	22.8 (14.1, 33.6)	0	0.0 (0.0, 4.6)	–		–
Increased temperature	4	5.1 (1.4, 12.5)	2	2.5 (0.3, 8.8) ≥39°C	1	1.3 (0.0, 7.2)	0	0.0 (0.0, 4.8) ≥39°C
Fatigue	–		–		18	24.0 (14.9, 35.3)	1	1.3 (0.0, 7.2)
Gastrointestinal disorder	–		–		7	9.3 (3.8, 18.3)	0	0.0 (0.0, 4.8)
Headache	–		–		24	32.0 (21.7, 43.8)	1	1.3 (0.0, 7.2)
Increased sweating	–		–		5	6.7 (2.2, 14.9)	0	0.0 (0.0, 4.8)
Joint pain	–		–		14	18.7 (10.6, 29.3)	0	0.0 (0.0, 4.8)
Muscle aches	–		–		34	45.3 (33.8, 57.3)	0	0.0 (0.0, 4.8)
Shivering (chills)	–		–		7	9.3 (3.8, 18.3)	2	2.7 (0.3, 9.3)

Reactogenicity and safety of AS03_B-adjuvanted H5N1 influenza vaccine in children: an open-label, one-way, crossover trial

Article Category: Brief communication

Published Online: Mar 21, 2018

Page range: 359 - 364

DOI: https://doi.org/10.1515/abm-2018-0008

Keywords
AS03 adjuvanted, children, H5N1, influenza, pandemic, safety, vaccine

© 2017 Patricia Izurieta, Pope Kosalaraksa, Louise Frenette, Mamadou Dramé, Bruce L. Innis, David W Vaughn, Anne Schuind

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Figure 1

Summary of unsolicited AEs in the TVC

Solicited injection site and general AEs in the TVC

Reactogenicity and safety of AS03B-adjuvanted H5N1 influenza vaccine in children: an open-label, one-way, crossover trial

Article Category: Brief communication

Published Online: Mar 21, 2018

Page range: 359 - 364

DOI: https://doi.org/10.1515/abm-2018-0008

KeywordsAS03 adjuvanted, children, H5N1, influenza, pandemic, safety, vaccine

© 2017 Patricia Izurieta, Pope Kosalaraksa, Louise Frenette, Mamadou Dramé, Bruce L. Innis, David W Vaughn, Anne Schuind

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Figure 1

Summary of unsolicited AEs in the TVC

Solicited injection site and general AEs in the TVC

Reactogenicity and safety of AS03_B-adjuvanted H5N1 influenza vaccine in children: an open-label, one-way, crossover trial

Keywords
AS03 adjuvanted, children, H5N1, influenza, pandemic, safety, vaccine