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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00978120
First received: September 15, 2009
Last updated: August 8, 2012
Last verified: August 2012
Results First Received: June 27, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: 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
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.
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.
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.
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  
Number of Participants  
[units: participants]
  110     107     87     86     390  
Age  
[units: participants]
         
<=18 years     22     23     12     10     67  
Between 18 and 65 years     80     79     67     68     294  
>=65 years     8     5     8     8     29  
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     72     62     52     45     231  
Male     38     45     35     41     159  
Region of Enrollment  
[units: participants]
         
United States     110     107     87     86     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  
Asthma Duration [2]
[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  
Body Mass Index (BMI) [3]
[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  
Forced Expiratory Volume in 1 second (FEV1) % Predicted [4]
[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  
Forced Vital Capacity (FVC) % Predicted [5]
[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  
FEV1/FVC Ratio [6]
[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 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.
[2] 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.
[3]

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

[4] 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.
[5] 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.
[6]

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
  Show All Outcome Measures

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 ]

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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


  Serious Adverse Events
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Time Frame Enrollment through last day of followup (Day 201, target last day)
Additional Description No text entered.

Reporting Groups
  Description
Mild/Moderate Asthma, Low Dose Vaccine (15 Mcg) Participants with mild/moderate asthma received one 15 mcg dose of unadjuvanted, 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/moderate asthma received two 15 mcg doses of unadjuvanted, inactivated Novartis H1N1 pandemic influenza vaccine by intramuscular injection on Day 1 and Day 21.
Severe Asthma, Low Dose Vaccine (15mcg) Participants with severe asthma received one 15 mcg dose of unadjuvanted, 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, inactivated Novartis H1N1 pandemic influenza vaccine by intramuscular injection on Day 1 and Day 21.

Serious Adverse Events
    Mild/Moderate Asthma, Low Dose Vaccine (15 Mcg)     Mild/Moderate Asthma, High Dose Vaccine (30mcg)     Severe Asthma, Low Dose Vaccine (15mcg)     Severe Asthma, High Dose Vaccine (30mcg)  
Total, serious adverse events          
# participants affected / at risk     4.0/110.0 (3.64%)     4.0/107.0 (3.74%)     12.0/87.0 (13.79%)     6.0/86.0 (6.98%)  
Cardiac disorders          
Atrial flutter † 1        
# participants affected / at risk     1/110 (0.91%)     0/107 (0.00%)     0/87 (0.00%)     0/86 (0.00%)  
# events     1     0     0     0  
Gastrointestinal disorders          
Pancreatitis † 1        
# participants affected / at risk     0/110 (0.00%)     0/107 (0.00%)     0/87 (0.00%)     1/86 (1.16%)  
# events     0     0     0     1  
Small intestinal obstruction † 1        
# participants affected / at risk     0/110 (0.00%)     0/107 (0.00%)     1/87 (1.15%)     0/86 (0.00%)  
# events     0     0     1     0  
Umbilical hernia † 1        
# participants affected / at risk     0/110 (0.00%)     0/107 (0.00%)     0/87 (0.00%)     1/86 (1.16%)  
# events     0     0     0     1  
General disorders          
Abasia † 1        
# participants affected / at risk     0/110 (0.00%)     0/107 (0.00%)     1/87 (1.15%)     0/86 (0.00%)  
# events     0     0     1     0  
Chest pain † 1        
# participants affected / at risk     0/110 (0.00%)     0/107 (0.00%)     1/87 (1.15%)     0/86 (0.00%)  
# events     0     0     1     0  
Death † 1        
# participants affected / at risk     0/110 (0.00%)     0/107 (0.00%)     0/87 (0.00%)     1/86 (1.16%)  
# events     0     0     0     1  
Infections and infestations          
Diverticulitis † 1        
# participants affected / at risk     0/110 (0.00%)     0/107 (0.00%)     1/87 (1.15%)     0/86 (0.00%)  
# events     0     0     1     0  
Localised infection † 1        
# participants affected / at risk     0/110 (0.00%)     0/107 (0.00%)     1/87 (1.15%)     0/86 (0.00%)  
# events     0     0     1     0  
Pneumonia † 1        
# participants affected / at risk     1/110 (0.91%)     1/107 (0.93%)     0/87 (0.00%)     0/86 (0.00%)  
# events     1     1     0     0  
Injury, poisoning and procedural complications          
Road traffic accident † 1        
# participants affected / at risk     0/110 (0.00%)     1/107 (0.93%)     0/87 (0.00%)     0/86 (0.00%)  
# events     0     1     0     0  
Musculoskeletal and connective tissue disorders          
Pain in extremity † 1        
# participants affected / at risk     0/110 (0.00%)     1/107 (0.93%)     0/87 (0.00%)     0/86 (0.00%)  
# events     0     1     0     0  
Spinal osteoarthritis † 1        
# participants affected / at risk     1/110 (0.91%)     0/107 (0.00%)     0/87 (0.00%)     0/86 (0.00%)  
# events     1     0     0     0  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)          
Breast cancer † 1        
# participants affected / at risk     0/110 (0.00%)     0/107 (0.00%)     1/87 (1.15%)     0/86 (0.00%)  
# events     0     0     1     0  
Thyroid cancer † 1        
# participants affected / at risk     0/110 (0.00%)     0/107 (0.00%)     1/87 (1.15%)     0/86 (0.00%)  
# events     0     0     1     0  
Reproductive system and breast disorders          
Ovarian cyst † 1        
# participants affected / at risk     0/110 (0.00%)     1/107 (0.93%)     0/87 (0.00%)     0/86 (0.00%)  
# events     0     1     0     0  
Respiratory, thoracic and mediastinal disorders          
Asthma † 1        
# participants affected / at risk     1/110 (0.91%)     0/107 (0.00%)     7/87 (8.05%)     3/86 (3.49%)  
# events     1     0     7     3  
Surgical and medical procedures          
Drug rehabilitation † 1        
# participants affected / at risk     0/110 (0.00%)     0/107 (0.00%)     1/87 (1.15%)     0/86 (0.00%)  
# events     0     0     1     0  
Hysterectomy † 1        
# participants affected / at risk     0/110 (0.00%)     1/107 (0.93%)     0/87 (0.00%)     0/86 (0.00%)  
# events     0     1     0     0  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA 12.1




  Other Adverse Events


  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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