Trial Outcomes & Findings for Study to Evaluate the Potential Effect of Benralizumab on the Humoral Immune Response to the Seasonal Influenza Vaccination in Adolescent and Young Adult Patients With Severe Asthma (NCT NCT02814643)

NCT ID: NCT02814643

Last Updated: 2018-10-24

Results Overview

To compare the geometric mean fold rises in influenza strain-specific hemagglutination-inhibition responses from Week 8 to Week 12 between patients receiving benralizumab 30mg and patients receiving placebo. Geometric mean fold rise was defined as antilog(z) (mean \[log(z) x\]), where "x" is the postdose HAI antibody titer fold rise from Week 8 and "z" is the natural logarithm.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 103 participants
• Primary outcome timeframe: 4 weeks
• Results posted on: 2018-10-24

Participant Flow

This study was conducted at 30 study centers in the United States between 01 July 2016 and 24 January 2017

The study duration was up to 23 weeks, consisting of an initial screening period lasting up to 3 weeks, a 12-week treatment period, and a follow-up visit 8 weeks after the last dose of study drug

Participant milestones

Measure	Benralizumab 30mg Benralizumab 30mg/day subcutaneous	Placebo Placebo to benralizumab subcutaneous
Overall Study STARTED	51	52
Overall Study COMPLETED	50	49
Overall Study NOT COMPLETED	1	3

Reasons for withdrawal

Measure	Benralizumab 30mg Benralizumab 30mg/day subcutaneous	Placebo Placebo to benralizumab subcutaneous
Overall Study Lost to Follow-up	0	1
Overall Study Withdrawal by Subject	1	2

Baseline Characteristics

Study to Evaluate the Potential Effect of Benralizumab on the Humoral Immune Response to the Seasonal Influenza Vaccination in Adolescent and Young Adult Patients With Severe Asthma

Baseline characteristics by cohort

Measure	Benralizumab 30mg n=51 Participants Benralizumab 30mg/day subcutaneous	Placebo n=52 Participants Placebo to benralizumab subcutaneous	Total n=103 Participants Total of all reporting groups
Age, Continuous	16.0 Years STANDARD_DEVIATION 2.65 • n=5 Participants	15.7 Years STANDARD_DEVIATION 2.99 • n=7 Participants	15.9 Years STANDARD_DEVIATION 2.82 • n=5 Participants
Age, Customized ≥12 to ≤17	36 Participants n=5 Participants	36 Participants n=7 Participants	72 Participants n=5 Participants
Age, Customized ≥18 to ≤21	15 Participants n=5 Participants	16 Participants n=7 Participants	31 Participants n=5 Participants
Sex/Gender, Customized Female	21 Participants n=5 Participants	21 Participants n=7 Participants	42 Participants n=5 Participants
Sex/Gender, Customized Male	30 Participants n=5 Participants	31 Participants n=7 Participants	61 Participants n=5 Participants
Race/Ethnicity, Customized American Indian Or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Black Or African American	13 Participants n=5 Participants	13 Participants n=7 Participants	26 Participants n=5 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized White	38 Participants n=5 Participants	36 Participants n=7 Participants	74 Participants n=5 Participants

PRIMARY outcome

Timeframe: 4 weeks

Population: The vaccine immunogenicity analysis set included all randomized patients who received ≥1 dose of planned study drugs, had pre- (Week 8) and postdose (Week 12) HAI or microneutralization antibody measurements, and had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an antibody response.

To compare the geometric mean fold rises in influenza strain-specific hemagglutination-inhibition responses from Week 8 to Week 12 between patients receiving benralizumab 30mg and patients receiving placebo. Geometric mean fold rise was defined as antilog(z) (mean [log(z) x]), where "x" is the postdose HAI antibody titer fold rise from Week 8 and "z" is the natural logarithm.

Outcome measures

Measure	Benralizumab 30mg n=50 Participants Benralizumab 30mg/day subcutaneous	Placebo n=49 Participants Placebo to benralizumab subcutaneous
Postdose Strain-specific Hemagglutination-inhibition (HAI) Antibody Geometric Mean Fold Rise From Week 8 to Week 12 Influenza A H1N1	3.60 Fold change Standard Error 1.22	3.13 Fold change Standard Error 1.22
Postdose Strain-specific Hemagglutination-inhibition (HAI) Antibody Geometric Mean Fold Rise From Week 8 to Week 12 Influenza A H3N2	3.25 Fold change Standard Error 1.18	3.85 Fold change Standard Error 1.18
Postdose Strain-specific Hemagglutination-inhibition (HAI) Antibody Geometric Mean Fold Rise From Week 8 to Week 12 Influenza B Yamagata lineage	3.42 Fold change Standard Error 1.16	3.17 Fold change Standard Error 1.16
Postdose Strain-specific Hemagglutination-inhibition (HAI) Antibody Geometric Mean Fold Rise From Week 8 to Week 12 Influenza B Victoria lineage	4.08 Fold change Standard Error 1.19	3.27 Fold change Standard Error 1.19

PRIMARY outcome

Timeframe: 12 weeks

Population: The vaccine immunogenicity analysis set included all randomized patients who received at least 1 dose of planned study drugs, had pre- (Week 8) and postdose (Week 12) HAI or MN antibody measurements, and had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an antibody response.

To compare the geometric mean titers of hemagglutination-inhibition antibody as a measure of influenza strain-specific response at Week 12 between patients receiving benralizumab 30mg and patients receiving placebo.

Outcome measures

Measure	Benralizumab 30mg n=50 Participants Benralizumab 30mg/day subcutaneous	Placebo n=49 Participants Placebo to benralizumab subcutaneous
Postdose Strain-specific Hemagglutination-inhibition Antibody Geometric Mean Titers Obtained at Week 12 Influenza A H1N1	521.06 Antibody titer Standard Error 1.13	518.60 Antibody titer Standard Error 1.13
Postdose Strain-specific Hemagglutination-inhibition Antibody Geometric Mean Titers Obtained at Week 12 Influenza A H3N2	170.73 Antibody titer Standard Error 1.15	219.35 Antibody titer Standard Error 1.15
Postdose Strain-specific Hemagglutination-inhibition Antibody Geometric Mean Titers Obtained at Week 12 Influenza B Yamagata lineage	61.47 Antibody titer Standard Error 1.13	63.15 Antibody titer Standard Error 1.13
Postdose Strain-specific Hemagglutination-inhibition Antibody Geometric Mean Titers Obtained at Week 12 Influenza B Victoria lineage	53.10 Antibody titer Standard Error 1.14	66.85 Antibody titer Standard Error 1.14

PRIMARY outcome

Timeframe: 4 weeks

Population: The vaccine immunogenicity analysis set included all randomized patients who received at least 1 dose of planned study drugs, had pre- (Week 8) and postdose (Week 12) HAI or MN antibody measurements, and had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an antibody response.

To compare the proportions of patients experiencing influenza strain-specific responses as measured by ≥4-fold rises in hemagglutination-inhibition antibody titer from Week 8 to Week 12 between patients receiving benralizumab 30mg and patients receiving placebo.

Outcome measures

Measure	Benralizumab 30mg n=50 Participants Benralizumab 30mg/day subcutaneous	Placebo n=49 Participants Placebo to benralizumab subcutaneous
Proportion of Patients Who Experienced a Strain-specific Postdose Antibody Response at Week 12 With Antibody Response Defined as a ≥4-fold Rise in Hemagglutination-inhibition Antibody Titer From Week 8 to Week 12 Influenza A H1N1	0.440 Proportion of Participants Interval 0.32 to 0.57	0.306 Proportion of Participants Interval 0.2 to 0.43
Proportion of Patients Who Experienced a Strain-specific Postdose Antibody Response at Week 12 With Antibody Response Defined as a ≥4-fold Rise in Hemagglutination-inhibition Antibody Titer From Week 8 to Week 12 Influenza A H3N2	0.500 Proportion of Participants Interval 0.38 to 0.62	0.490 Proportion of Participants Interval 0.37 to 0.62
Proportion of Patients Who Experienced a Strain-specific Postdose Antibody Response at Week 12 With Antibody Response Defined as a ≥4-fold Rise in Hemagglutination-inhibition Antibody Titer From Week 8 to Week 12 Influenza B Yamagata lineage	0.480 Proportion of Participants Interval 0.36 to 0.6	0.490 Proportion of Participants Interval 0.37 to 0.62
Proportion of Patients Who Experienced a Strain-specific Postdose Antibody Response at Week 12 With Antibody Response Defined as a ≥4-fold Rise in Hemagglutination-inhibition Antibody Titer From Week 8 to Week 12 Influenza B Victoria lineage	0.560 Proportion of Participants Interval 0.43 to 0.68	0.408 Proportion of Participants Interval 0.29 to 0.54

PRIMARY outcome

Timeframe: 12 weeks

Population: The vaccine immunogenicity analysis set included all randomized patients who received at least 1 dose of planned study drugs, had pre- (Week 8) and postdose (Week 12) HAI or MN antibody measurements, and had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an antibody response.

To compare the proportions of patients experiencing influenza strain-specific responses as measured by ≥40-fold rises in hemagglutination-inhibition antibody titer at Week 12 between patients receiving benralizumab 30mg and patients receiving placebo.

Outcome measures

Measure	Benralizumab 30mg n=50 Participants Benralizumab 30mg/day subcutaneous	Placebo n=49 Participants Placebo to benralizumab subcutaneous
Proportion of Patients Who Achieved a Strain-specific Postdose Hemagglutination-inhibition Antibody Titer ≥40 at Week 12 Influenza A H1N1	1.00 Proportion of Participants 90% Confidence Interval 251.9 • Interval 0.94 to 1.0	1.00 Proportion of Participants 90% Confidence Interval 191.3 • Interval 0.94 to 1.0
Proportion of Patients Who Achieved a Strain-specific Postdose Hemagglutination-inhibition Antibody Titer ≥40 at Week 12 Influenza A H3N2	0.980 Proportion of Participants 90% Confidence Interval 136.2 • Interval 0.91 to 1.0	0.980 Proportion of Participants 90% Confidence Interval 168.6 • Interval 0.91 to 1.0
Proportion of Patients Who Achieved a Strain-specific Postdose Hemagglutination-inhibition Antibody Titer ≥40 at Week 12 Influenza B Yamagata lineage	0.860 Proportion of Participants 90% Confidence Interval 144.9 • Interval 0.75 to 0.93	0.796 Proportion of Participants 90% Confidence Interval 115.0 • Interval 0.68 to 0.88
Proportion of Patients Who Achieved a Strain-specific Postdose Hemagglutination-inhibition Antibody Titer ≥40 at Week 12 Influenza B Victoria lineage	0.780 Proportion of Participants 90% Confidence Interval 178.7 • Interval 0.66 to 0.87	0.878 Proportion of Participants 90% Confidence Interval 162.2 • Interval 0.77 to 0.95

SECONDARY outcome

Timeframe: 12 weeks

Population: The vaccine immunogenicity analysis set included all randomized patients who received at least 1 dose of planned study drugs, had pre- (Week 8) and postdose (Week 12) HAI or MN antibody measurements, and had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an antibody response.

To compare the proportions of patients experiencing influenza strain-specific responses as measured by ≥320-fold rises in hemagglutination-inhibition antibody titer at Week 12 between patients receiving benralizumab 30mg and patients receiving placebo.

Outcome measures

Measure	Benralizumab 30mg n=50 Participants Benralizumab 30mg/day subcutaneous	Placebo n=49 Participants Placebo to benralizumab subcutaneous
Proportion of Patients Who Achieved a Strain-specific Postdose Hemagglutination Inhibition Antibody Titre ≥320 at Week 12 Influenza A H1N1	0.840 Proportion of Participants Interval 0.73 to 0.92	0.857 Proportion of Participants Interval 0.75 to 0.93
Proportion of Patients Who Achieved a Strain-specific Postdose Hemagglutination Inhibition Antibody Titre ≥320 at Week 12 Influenza B Victoria lineage	0.080 Proportion of Participants Interval 0.03 to 0.17	0.041 Proportion of Participants Interval 0.01 to 0.12
Proportion of Patients Who Achieved a Strain-specific Postdose Hemagglutination Inhibition Antibody Titre ≥320 at Week 12 Influenza A H3N2	0.500 Proportion of Participants Interval 0.38 to 0.62	0.612 Proportion of Participants Interval 0.48 to 0.73
Proportion of Patients Who Achieved a Strain-specific Postdose Hemagglutination Inhibition Antibody Titre ≥320 at Week 12 Influenza B Yamagata lineage	0.020 Proportion of Participants Interval 0.0 to 0.09	0.020 Proportion of Participants Interval 0.0 to 0.09

SECONDARY outcome

Timeframe: 4 weeks

Population: The vaccine immunogenicity analysis set included all randomized patients who received at least 1 dose of planned study drugs, had pre- (Week 8) and postdose (Week 12) HAI or MN antibody measurements, and had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an antibody response.

To compare the geometric mean fold rises in influenza strain-specific microneutralization antibody responses from Week 8 to Week 12 between patients receiving benralizumab 30mg and patients receiving placebo. Geometric mean fold rise was defined as antilog(z) (mean [log(z) x]), where "x" is the postdose microneutralization antibody titer fold rise from Week 8 and "z" is the natural logarithm.

Outcome measures

Measure	Benralizumab 30mg n=50 Participants Benralizumab 30mg/day subcutaneous	Placebo n=49 Participants Placebo to benralizumab subcutaneous
Postdose Strain-specific Microneutralization Antibody Geometric Mean Fold Rise From Week 8 to Week 12 Influenza A H1N1	5.1 Fold change Geometric Coefficient of Variation 521.4	4.4 Fold change Geometric Coefficient of Variation 329.4
Postdose Strain-specific Microneutralization Antibody Geometric Mean Fold Rise From Week 8 to Week 12 Influenza A H3N2	3.2 Fold change Geometric Coefficient of Variation 149.8	3.6 Fold change Geometric Coefficient of Variation 210.0
Postdose Strain-specific Microneutralization Antibody Geometric Mean Fold Rise From Week 8 to Week 12 Influenza B Yamagata lineage	2.8 Fold change Geometric Coefficient of Variation 148.9	3.2 Fold change Geometric Coefficient of Variation 141.3
Postdose Strain-specific Microneutralization Antibody Geometric Mean Fold Rise From Week 8 to Week 12 Influenza B Victoria lineage	3.8 Fold change Geometric Coefficient of Variation 224.1	3.5 Fold change Geometric Coefficient of Variation 195.3

SECONDARY outcome

Timeframe: 12 weeks

Population: The vaccine immunogenicity analysis set included all randomized patients who received at least 1 dose of planned study drugs, had pre- (Week 8) and postdose (Week 12) HAI or MN antibody measurements, and had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an antibody response.

To compare the geometric mean titers of microneutralization antibody as a measure of influenza strain-specific response at Week 12 between patients receiving benralizumab 30mg and patients receiving placebo.

Outcome measures

Measure	Benralizumab 30mg n=50 Participants Benralizumab 30mg/day subcutaneous	Placebo n=49 Participants Placebo to benralizumab subcutaneous
Postdose Strain-specific Serum Microneutralization Antibody Geometric Mean Titers Obtained at Week 12 Influenza A H1N1	3774.1 Antibody titer Geometric Coefficient of Variation 181.7	3969.1 Antibody titer Geometric Coefficient of Variation 154.0
Postdose Strain-specific Serum Microneutralization Antibody Geometric Mean Titers Obtained at Week 12 Influenza A H3N2	4307.5 Antibody titer Geometric Coefficient of Variation 169.0	4351.3 Antibody titer Geometric Coefficient of Variation 171.0
Postdose Strain-specific Serum Microneutralization Antibody Geometric Mean Titers Obtained at Week 12 Influenza B Yamagata lineage	350.2 Antibody titer Geometric Coefficient of Variation 103.6	336.2 Antibody titer Geometric Coefficient of Variation 114.3
Postdose Strain-specific Serum Microneutralization Antibody Geometric Mean Titers Obtained at Week 12 Influenza B Victoria lineage	164.5 Antibody titer Geometric Coefficient of Variation 178.5	234.4 Antibody titer Geometric Coefficient of Variation 135.0

SECONDARY outcome

Timeframe: 4 weeks

Population: The vaccine immunogenicity analysis set included all randomized patients who received at least 1 dose of planned study drugs, had pre- (Week 8) and postdose (Week 12) HAI or MN antibody measurements, and had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an antibody response.

To compare the proportions of patients experiencing influenza strain-specific responses as measured by ≥4-fold rises in microneutralization antibody titer from Week 8 to Week 12 between patients receiving benralizumab 30mg and patients receiving placebo.

Outcome measures

Measure	Benralizumab 30mg n=50 Participants Benralizumab 30mg/day subcutaneous	Placebo n=49 Participants Placebo to benralizumab subcutaneous
Proportion of Patients Who Experience a Strain-specific Postdose Antibody Response at Week 12 With Antibody Response Defined as a ≥4-fold Rise in Microneutralization Antibody Titer From Week 8 to Week 12 Influenza A H1N1	0.420 Proportion of Participants 90% Confidence Interval 251.9 • Interval 0.3 to 0.55	0.408 Proportion of Participants 90% Confidence Interval 191.3 • Interval 0.29 to 0.54
Proportion of Patients Who Experience a Strain-specific Postdose Antibody Response at Week 12 With Antibody Response Defined as a ≥4-fold Rise in Microneutralization Antibody Titer From Week 8 to Week 12 Influenza A H3N2	0.440 Proportion of Participants 90% Confidence Interval 136.2 • Interval 0.32 to 0.57	0.429 Proportion of Participants 90% Confidence Interval 168.6 • Interval 0.31 to 0.56
Proportion of Patients Who Experience a Strain-specific Postdose Antibody Response at Week 12 With Antibody Response Defined as a ≥4-fold Rise in Microneutralization Antibody Titer From Week 8 to Week 12 Influenza B Yamagata lineage	0.280 Proportion of Participants 90% Confidence Interval 144.9 • Interval 0.18 to 0.4	0.388 Proportion of Participants 90% Confidence Interval 115.0 • Interval 0.27 to 0.52
Proportion of Patients Who Experience a Strain-specific Postdose Antibody Response at Week 12 With Antibody Response Defined as a ≥4-fold Rise in Microneutralization Antibody Titer From Week 8 to Week 12 Influenza B Victoria lineage	0.400 Proportion of Participants 90% Confidence Interval 178.7 • Interval 0.28 to 0.53	0.388 Proportion of Participants 90% Confidence Interval 162.2 • Interval 0.27 to 0.52

SECONDARY outcome

Timeframe: 12 weeks

Population: The full analysis set included all patients who were randomized and received any investigational product.

To compare the change from baseline at Week 12 in mean ACQ-6 score between patients receiving benralizumab 30mg and patients receiving placebo. The ACQ-6 assesses asthma symptoms (nighttime waking, symptoms on waking, activity limitation, shortness of breath, wheezing, and short-acting β2 agonist use). Questions are weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ-6 score is the mean of the responses to each question. Mean scores of ≤0.75 indicate well-controlled asthma, scores between 0.75 and ≤1.5 indicate partly controlled asthma, and a score >1.5 indicates not well controlled asthma

Outcome measures

Measure	Benralizumab 30mg n=50 Participants Benralizumab 30mg/day subcutaneous	Placebo n=49 Participants Placebo to benralizumab subcutaneous
Change From Baseline in Mean Asthma Control Questionnaire 6 (ACQ-6) Score at Week 12	-0.50 Score on a scale Interval -2.8 to 4.3	-0.42 Score on a scale Interval -2.7 to 1.2

Adverse Events

Benralizumab 30mg

Serious events: 0 serious events

Other events: 28 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Measure	Benralizumab 30mg n=51 participants at risk Benralizumab 30mg/day subcutaneous	Placebo n=52 participants at risk Placebo to benralizumab subcutaneous
Psychiatric disorders Suicidal ideation	0.00% 0/51 • All AEs, including SAEs, were collected from the time the patient, parent, or legal guardian signed the informed consent/assent throughout the treatment period and including the follow-up period (through Week 20).	1.9% 1/52 • Number of events 1 • All AEs, including SAEs, were collected from the time the patient, parent, or legal guardian signed the informed consent/assent throughout the treatment period and including the follow-up period (through Week 20).
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/51 • All AEs, including SAEs, were collected from the time the patient, parent, or legal guardian signed the informed consent/assent throughout the treatment period and including the follow-up period (through Week 20).	1.9% 1/52 • Number of events 1 • All AEs, including SAEs, were collected from the time the patient, parent, or legal guardian signed the informed consent/assent throughout the treatment period and including the follow-up period (through Week 20).

Other adverse events

Measure	Benralizumab 30mg n=51 participants at risk Benralizumab 30mg/day subcutaneous	Placebo n=52 participants at risk Placebo to benralizumab subcutaneous
Gastrointestinal disorders Abdominal discomfort	3.9% 2/51 • Number of events 2 • All AEs, including SAEs, were collected from the time the patient, parent, or legal guardian signed the informed consent/assent throughout the treatment period and including the follow-up period (through Week 20).	0.00% 0/52 • All AEs, including SAEs, were collected from the time the patient, parent, or legal guardian signed the informed consent/assent throughout the treatment period and including the follow-up period (through Week 20).
Gastrointestinal disorders Nausea	2.0% 1/51 • Number of events 1 • All AEs, including SAEs, were collected from the time the patient, parent, or legal guardian signed the informed consent/assent throughout the treatment period and including the follow-up period (through Week 20).	3.8% 2/52 • Number of events 2 • All AEs, including SAEs, were collected from the time the patient, parent, or legal guardian signed the informed consent/assent throughout the treatment period and including the follow-up period (through Week 20).
Infections and infestations Gastroenteritis viral	5.9% 3/51 • Number of events 3 • All AEs, including SAEs, were collected from the time the patient, parent, or legal guardian signed the informed consent/assent throughout the treatment period and including the follow-up period (through Week 20).	1.9% 1/52 • Number of events 1 • All AEs, including SAEs, were collected from the time the patient, parent, or legal guardian signed the informed consent/assent throughout the treatment period and including the follow-up period (through Week 20).
Infections and infestations Nasopharyngitis	3.9% 2/51 • Number of events 2 • All AEs, including SAEs, were collected from the time the patient, parent, or legal guardian signed the informed consent/assent throughout the treatment period and including the follow-up period (through Week 20).	7.7% 4/52 • Number of events 5 • All AEs, including SAEs, were collected from the time the patient, parent, or legal guardian signed the informed consent/assent throughout the treatment period and including the follow-up period (through Week 20).
Infections and infestations Sinusitis	3.9% 2/51 • Number of events 2 • All AEs, including SAEs, were collected from the time the patient, parent, or legal guardian signed the informed consent/assent throughout the treatment period and including the follow-up period (through Week 20).	1.9% 1/52 • Number of events 1 • All AEs, including SAEs, were collected from the time the patient, parent, or legal guardian signed the informed consent/assent throughout the treatment period and including the follow-up period (through Week 20).
Infections and infestations Upper respiratory tract infection	5.9% 3/51 • Number of events 4 • All AEs, including SAEs, were collected from the time the patient, parent, or legal guardian signed the informed consent/assent throughout the treatment period and including the follow-up period (through Week 20).	1.9% 1/52 • Number of events 1 • All AEs, including SAEs, were collected from the time the patient, parent, or legal guardian signed the informed consent/assent throughout the treatment period and including the follow-up period (through Week 20).
Infections and infestations Viral upper respiratory tract infection	3.9% 2/51 • Number of events 2 • All AEs, including SAEs, were collected from the time the patient, parent, or legal guardian signed the informed consent/assent throughout the treatment period and including the follow-up period (through Week 20).	0.00% 0/52 • All AEs, including SAEs, were collected from the time the patient, parent, or legal guardian signed the informed consent/assent throughout the treatment period and including the follow-up period (through Week 20).
Injury, poisoning and procedural complications Ligament sprain	3.9% 2/51 • Number of events 2 • All AEs, including SAEs, were collected from the time the patient, parent, or legal guardian signed the informed consent/assent throughout the treatment period and including the follow-up period (through Week 20).	0.00% 0/52 • All AEs, including SAEs, were collected from the time the patient, parent, or legal guardian signed the informed consent/assent throughout the treatment period and including the follow-up period (through Week 20).
Musculoskeletal and connective tissue disorders Costochondritis	3.9% 2/51 • Number of events 3 • All AEs, including SAEs, were collected from the time the patient, parent, or legal guardian signed the informed consent/assent throughout the treatment period and including the follow-up period (through Week 20).	0.00% 0/52 • All AEs, including SAEs, were collected from the time the patient, parent, or legal guardian signed the informed consent/assent throughout the treatment period and including the follow-up period (through Week 20).
Nervous system disorders Headache	3.9% 2/51 • Number of events 3 • All AEs, including SAEs, were collected from the time the patient, parent, or legal guardian signed the informed consent/assent throughout the treatment period and including the follow-up period (through Week 20).	7.7% 4/52 • Number of events 4 • All AEs, including SAEs, were collected from the time the patient, parent, or legal guardian signed the informed consent/assent throughout the treatment period and including the follow-up period (through Week 20).
Respiratory, thoracic and mediastinal disorders Asthma	5.9% 3/51 • Number of events 5 • All AEs, including SAEs, were collected from the time the patient, parent, or legal guardian signed the informed consent/assent throughout the treatment period and including the follow-up period (through Week 20).	5.8% 3/52 • Number of events 3 • All AEs, including SAEs, were collected from the time the patient, parent, or legal guardian signed the informed consent/assent throughout the treatment period and including the follow-up period (through Week 20).
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/51 • All AEs, including SAEs, were collected from the time the patient, parent, or legal guardian signed the informed consent/assent throughout the treatment period and including the follow-up period (through Week 20).	5.8% 3/52 • Number of events 3 • All AEs, including SAEs, were collected from the time the patient, parent, or legal guardian signed the informed consent/assent throughout the treatment period and including the follow-up period (through Week 20).
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.9% 3/51 • Number of events 4 • All AEs, including SAEs, were collected from the time the patient, parent, or legal guardian signed the informed consent/assent throughout the treatment period and including the follow-up period (through Week 20).	3.8% 2/52 • Number of events 2 • All AEs, including SAEs, were collected from the time the patient, parent, or legal guardian signed the informed consent/assent throughout the treatment period and including the follow-up period (through Week 20).
Skin and subcutaneous tissue disorders Acne	2.0% 1/51 • Number of events 1 • All AEs, including SAEs, were collected from the time the patient, parent, or legal guardian signed the informed consent/assent throughout the treatment period and including the follow-up period (through Week 20).	3.8% 2/52 • Number of events 2 • All AEs, including SAEs, were collected from the time the patient, parent, or legal guardian signed the informed consent/assent throughout the treatment period and including the follow-up period (through Week 20).

Additional Information

Mitchell Goldman MD, PhD

AstraZeneca

Phone: +1 610 457 5585

Email: Mitchell.Goldman@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee At least 30 days prior to submission for publication/presentation, Institution and PI shall jointly provide AZ with material for review. No publication/presentation may include any of AZ's Confidential Information without AZ's written approval. AZ can request Institution and PI to withhold material from submission for publication/presentation for an additional 90 days to allow AZ to establish and preserve its proprietary rights in the material being submitted for publication/presentation.
• Publication restrictions are in place

Restriction type: OTHER