Safety and Efficacy of an H1N1 Influenza Vaccine in People With Asthma

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ClinicalTrials.gov Identifier: NCT00978120

Recruitment Status : Completed

First Posted : September 16, 2009

Results First Posted : August 6, 2012

Last Update Posted : August 10, 2012

Sponsor:

Collaborator:

National Heart, Lung, and Blood Institute (NHLBI)

Information provided by (Responsible Party):

National Institute of Allergy and Infectious Diseases (NIAID)

Study Type:	Interventional
Study Design:	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Prevention
Condition:	H1N1 Influenza Virus
Interventions:	Biological: H1N1 vaccine high dose Biological: H1N1 vaccine low dose

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Study participants were recruited from October 16 to November 13, 2009 at the seven National Heart, Lung, and Blood Institute (NHLBI)- funded Severe Asthma Research Program sites.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups

	Description
Mild/Moderate Asthma, Low Dose Vaccine (15mcg)	Participants with mild-to-moderate asthma received one 15 micrograms (mcg) dose of unadjuvanted,[1] inactivated Novartis H1N1 pandemic influenza vaccine by intramuscular injection on Day 1 and Day 21.
Mild/Moderate Asthma, High Dose Vaccine (30mcg)	Participants with mild-to-moderate asthma received two 15 mcg doses of unadjuvanted,[1] inactivated Novartis H1N1 pandemic influenza vaccine by intramuscular injections on Day 1 and Day 21.
Severe Asthma, Low Dose Vaccine (15mcg)	Participants with severe asthma received one 15 mcg dose of unadjuvanted,[1] inactivated Novartis H1N1 pandemic influenza vaccine by intramuscular injection on Day 1 and Day 21.
Severe Asthma, High Dose Vaccine (30mcg)	Participants with severe asthma received two 15 mcg doses of unadjuvanted,[1] inactivated Novartis H1N1 pandemic influenza vaccine by intramuscular injections on Day 1 and Day 21. [1] Unadjuvanted: No agents added to, or used in conjunction with, vaccine antigens to augment or potentiate (and possibly target) the specific immune response to the antigen. (U.S. Food And Drug Administration)

Participant Flow: Overall Study

	Mild/Moderate Asthma, Low Dose Vaccine (15mcg)	Mild/Moderate Asthma, High Dose Vaccine (30mcg)	Severe Asthma, Low Dose Vaccine (15mcg)	Severe Asthma, High Dose Vaccine (30mcg)
STARTED	110	107	87	86
COMPLETED	108	107	84	84
NOT COMPLETED	2	0	3	2
Death	0	0	0	1
Lost to Follow-up	0	0	3	0
Withdrawal by Subject	2	0	0	0
Moved out of state	0	0	0	1

Baseline Characteristics

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Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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Reporting Groups

	Description
Mild/Moderate Asthma, Low Dose Vaccine (15mcg)	Participants with mild-to-moderate asthma received one 15 micrograms (mcg) dose of unadjuvanted,[1] inactivated Novartis H1N1 pandemic influenza vaccine by intramuscular injection on Day 1 and Day 21.
Mild/Moderate Asthma, High Dose Vaccine (30mcg)	Participants with mild-to-moderate asthma received two 15 mcg doses of unadjuvanted,[1] inactivated Novartis H1N1 pandemic influenza vaccine by intramuscular injections on Day 1 and Day 21.
Severe Asthma, Low Dose Vaccine (15mcg)	Participants with severe asthma received one 15 mcg dose of unadjuvanted,[1] inactivated Novartis H1N1 pandemic influenza vaccine by intramuscular injection on Day 1 and Day 21.
Severe Asthma, High Dose Vaccine (30mcg)	Participants with severe asthma received two 15 mcg doses of unadjuvanted,[1] inactivated Novartis H1N1 pandemic influenza vaccine by intramuscular injections on Day 1 and Day 21. [1] Unadjuvanted: No agents added to, or used in conjunction with, vaccine antigens to augment or potentiate (and possibly target) the specific immune response to the antigen. (U.S. Food And Drug Administration)
Total	Total of all reporting groups

Baseline Measures

Mild/Moderate Asthma, Low Dose Vaccine (15mcg)

Mild/Moderate Asthma, High Dose Vaccine (30mcg)

Severe Asthma, Low Dose Vaccine (15mcg)

Severe Asthma, High Dose Vaccine (30mcg)

Total

Overall Participants Analyzed
[Units: Participants]

110

107

390

Age
[Units: Participants]

<=18 years

Between 18 and 65 years

294

>=65 years

Age
[Units: Years]
Mean (Standard Deviation)

39.1 (18.1)

36.3 (17.0)

45.2 (17.0)

46.5 (17.3)

41.3 (17.8)

Gender
[Units: Participants]

Female

231

Male

159

Region of Enrollment
[Units: Participants]

United States

110

107

390

Age at Asthma Onset ^[1]
[Units: Years]
Mean (Standard Deviation)

17.1 (17.0)

16.4 (14.9)

21.9 (19.7)

21.9 (20.1)

19.0 (17.9)

^[1]	The age at asthma onset is the age defined in years when the participant was told by a physician that he/she has asthma. This was calculated by subtracting the participant’s age at the baseline visit (visit 1) from the number of years the participant reported to have known having asthma.

Asthma Duration ^[1]
[Units: Years]
Mean (Standard Deviation)

21.9 (13.9)

19.9 (13.4)

23.3 (16.5)

24.6 (17.8)

22.3 (15.3)

^[1]	Asthma duration is the number of years since the participant was told by a physician that he/she has asthma as reported at the baseline visit, visit 1.

Body Mass Index (BMI) ^[1]
[Units: Kg/m^2]
Mean (Standard Deviation)

29.5 (8.5)

28.5 (6.8)

31.8 (9.7)

30.1 (8.0)

29.9 (8.3)

^[1]

BMI is a number calculated from a person’s height and weight that provides a reliable indicator of body fatness for most people. Higher values reflect greater amount of body fat. [1] In adults, a BMI less than 18.5 is underweight; 18.5 to 24.9 is a normal or healthy weight; greater than or equal to 25.0 is overweight. The height and weight was collected at baseline only.

[1]: Healthy Weight , Assessing Your Weight , Body Mass Index http://www.cdc.gov/healthyweight/assessing/bmi/index.html

Forced Expiratory Volume in 1 second (FEV1) % Predicted ^[1]
[Units: Percentage]
Mean (Standard Deviation)

83.8 (16.3)

86.6 (17.6)

72.6 (19.4)

69.8 (20.8)

79.0 (19.7)

^[1]

FEV1 is air volume exhaled in 1 second during spirometry. Asthma severity classification for trial: mild--pre-bronchodilator FEV1 ≥ 80% predicted requiring no/ low-moderate dose of inhaled glucocorticoids; moderate--pre-bronchodilator FEV1 <80% predicted requiring no/ low-moderate dose of inhaled glucocorticoids; severe--requiring high-dose inhaled glucocorticoids with/without continuous/near continuous oral glucocorticoids, or uncontrolled despite treatment. FEV1 percent of predicted value is FEV1 converted to a percentage of normal, based on height, weight, and race.

Forced Vital Capacity (FVC) % Predicted ^[1]
[Units: Percentage]
Mean (Standard Deviation)

92.6 (14.3)

94.3 (16.1)

85.0 (17.1)

80.9 (18.7)

88.8 (17.3)

^[1]	FVC is a lung function test that measures the total amount of air exhaled. The percent of predicted value is FVC converted to a percentage of normal, based on height, weight, and race. Estimates of severity of abnormalities in flow volume measured by FVC: Mild-65-80% of predicted value; Moderate-50-65% of predicted value; Severe-<50% of predicted value.

FEV1/FVC Ratio ^[1]
[Units: Ratio (x 100)]
Mean (Standard Deviation)

74.5 (9.07)

75.7 (8.99)

68.4 (10.91)

68.4 (11.76)

72.1 (10.62)

^[1]

The FEV1 (forced expiratory volume 1))/ FVC (forced vital capacity) ratio is used to evaluate airways obstructions since pure restrictive ventilatory defects cause an equal reduction in the FEV1 and the FVC. An FEV1/FVC ratio below 80% indicates airflow obstruction. Normal FEV1/FVC: 8 – 19 years of age=85%; 20-39 years of age=80%; 40- 59 years of age 75%; 60-80 years of age 70% [1]

[1]: National Asthma Education and Prevention Program Expert Panel Report 3, Guidelines for the Diagnosis and Management of Asthma. Oct. 2007. http://www.nhlbi.nih.gov/guidelines/asthma/asthsumm.pdf

Outcome Measures

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1. Primary:

Percentage of Participants With Serious Adverse Events (SAEs) Attributed To Vaccination [ Time Frame: Measured at Baseline Visit and Days 1, 8, 21, 28, 41, 80, 120, and 201 ]

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2. Primary:

Percentage of Participants With Reactogenicity Adverse Events (AEs) Status Post Vaccine 1 [ Time Frame: Days 1 through 8 ]

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3. Primary:

Percentage of Participants With Reactogenicity Adverse Events (AEs) Status Post Vaccine 2 [ Time Frame: Days 21 through 28 ]

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4. Primary:

Percentage of Participants With Asthma Exacerbations Status Post Vaccine 1 [ Time Frame: Days 1 to 8 ]

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5. Primary:

Percentage of Participants With Asthma Exacerbations Status Post Vaccination 2 [ Time Frame: Days 21 to 28 ]

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6. Primary:

Percentage of Participants With Seroconversion at Day 28 Following Two Administrations of Vaccination, Mild-Moderate Asthmatics [ Time Frame: Days 1 to 28 ]

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7. Primary:

Percentage of Participants With Seroconversion at Day 28 Following Two Administrations of Vaccination, Severe Asthmatics [ Time Frame: Days 1 to 28 ]

Show Outcome Measure 7

8. Primary:

Percentage of Participants With Seroconversion at Day 41 Following Two Administrations of Vaccination, Mild-Moderate Asthmatics [ Time Frame: Days 1 to 41 ]

Show Outcome Measure 8

9. Primary:

Percentage of Participants With Seroconversion at Day 41 Following Two Administrations of Vaccination, Severe Asthmatics [ Time Frame: Days 1 to 41 ]

Show Outcome Measure 9

10. Primary:

Percentage of Participants With Seroprotection at Day 28 Following Two Administrations of Vaccination, Mild-Moderate Asthmatics [ Time Frame: Days 1 to 28 ]

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11. Primary:

Percentage of Participants With Seroprotection at Day 28 Following Two Administrations of Vaccination, Severe Asthmatics [ Time Frame: Days 1 to 28 ]

Show Outcome Measure 11

12. Primary:

Percentage of Participants With Seroprotection at Day 41 Following Two Administrations of Vaccination, Mild-Moderate Asthmatics [ Time Frame: Days 1 to 41 ]

Show Outcome Measure 12

13. Primary:

Percentage of Participants With Seroprotection at Day 41 Following Two Administrations of Vaccination, Severe Asthmatics [ Time Frame: Days 1 to 41 ]

Show Outcome Measure 13

14. Secondary:

Percentage of Participants With Seroconversion at Day 21 Following Single Administration of Vaccination, Mild-Moderate Asthmatics [ Time Frame: Days 1 to 21 ]

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15. Secondary:

Percentage of Participants With Seroconversion at Day 21 Following Single Administration of Vaccination, Severe Asthmatics [ Time Frame: Days 1 to 21 ]

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16. Secondary:

Percentage of Participants With Seroprotection at Day 21 Following Single Administration of Vaccination, Mild-Moderate Asthmatics [ Time Frame: Days 1 to 21 ]

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Measure Type	Secondary
Measure Title	Percentage of Participants With Seroprotection at Day 21 Following Single Administration of Vaccination, Mild-Moderate Asthmatics
Measure Description	Percentage of participants with seroprotection defined as hemagglutination inhibition assay (HAI) antibody titer of 1:40 or greater against influenza H1N1 2009 virus following a single administration of the H1N1 vaccine at each dose, combined across age groups.
Time Frame	Days 1 to 21

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
Mild/Moderate Asthma, Low Dose Vaccine (15mcg)	Participants with mild-to-moderate asthma received one 15 micrograms (mcg) dose of unadjuvanted[1], inactivated Novartis H1N1 pandemic influenza vaccine by intramuscular injection on Day 1 and Day 21.
Mild/Moderate Asthma, High Dose Vaccine (30mcg)	Participants with mild-to-moderate asthma received two 15 mcg doses of unadjuvanted[1], inactivated Novartis H1N1 pandemic influenza vaccine by intramuscular injections on Day 1 and Day 21. [1] Unadjuvanted: No agents added to, or used in conjunction with, vaccine antigens to augment or potentiate (and possibly target) the specific immune response to the antigen. (U.S. Food And Drug Administration)

Description

Mild/Moderate Asthma, Low Dose Vaccine (15mcg)

Participants with mild-to-moderate asthma received one 15 micrograms (mcg) dose of unadjuvanted[1], inactivated Novartis H1N1 pandemic influenza vaccine by intramuscular injection on Day 1 and Day 21.

Mild/Moderate Asthma, High Dose Vaccine (30mcg)

Participants with mild-to-moderate asthma received two 15 mcg doses of unadjuvanted[1], inactivated Novartis H1N1 pandemic influenza vaccine by intramuscular injections on Day 1 and Day 21.

[1] Unadjuvanted: No agents added to, or used in conjunction with, vaccine antigens to augment or potentiate (and possibly target) the specific immune response to the antigen. (U.S. Food And Drug Administration)

Measured Values

	Mild/Moderate Asthma, Low Dose Vaccine (15mcg)	Mild/Moderate Asthma, High Dose Vaccine (30mcg)
Participants Analyzed [Units: Participants]	107	107
Percentage of Participants With Seroprotection at Day 21 Following Single Administration of Vaccination, Mild-Moderate Asthmatics [Units: Percentage of participants]	90.7	95.3

Statistical Analysis 1 for Percentage of Participants With Seroprotection at Day 21 Following Single Administration of Vaccination, Mild-Moderate Asthmatics

Groups ^[1]	All groups
Statistical Test Type ^[2]	Superiority or Other
Statistical Method ^[3]	Fisher Exact
P Value ^[4]	0.284

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
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[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
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[3]	Other relevant method information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
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17. Secondary:

Percentage of Participants With Seroprotection at Day 21 Following Single Administration of Vaccination, Severe Asthmatics [ Time Frame: Days 1 to 21 ]

Show Outcome Measure 17

Serious Adverse Events

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Other Adverse Events

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Limitations and Caveats

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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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