Upper Respiratory Tract Infections
Conditions
Keywords
Prophylaxis, Treatment, Symptoms, Winter Colds and Flu
Brief summary
The aim of the study is to see if lozenges containing a low dose of interferon-alpha can prevent and/or reduce the severity of colds and flu. Starting about 1 month before the expected start of the winter colds and flu season in Perth, Australia, healthy volunteers will allow a lozenge containing interferon, or a lozenge containing no medicine (a placebo), to dissolve in their mouth once a day for 16 weeks. Blood tests at the start and end of treatment will determine whether interferon was able to prevent infections with cold/flu viruses. Once a week, volunteers will complete a survey about their cold/flu symptoms, medications taken, days of work missed, etc. to see if interferon was able to make their winter colds and flu less severe.
Interventions
DRUGinterferon-alpha
a lozenge for oral dissolution containing 150 international units of human interferon-alpha taken once daily for 16 weeks
OTHERplacebo
placebo lozenges for oral dissolution taken once daily for 16 weeks
Sponsors
Department of Health, Western Australia
Ainos, Inc. (f/k/a Amarillo Biosciences Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Male or non-pregnant female * Females of child-bearing potential must practice a medically accepted form of birth control
Exclusion criteria
* Currently exhibiting an acute upper respiratory tract infection * history of chronic respiratory disease requiring regular therapy(i.e. COPD, asthma, bronchitis, etc.) * any condition likely to increase the risk of severe or complicated influenza (i.e. cardiac disease, chronic renal disease, endocrine diseases, including diabetes and/or immunosuppressive therapy) * any condition requiring regular treatment with antihistamines, analgesics or antipyretics * known infection with HIV, hepatitis B virus or hepatitis C virus * any other serious, uncontrolled disease * any active infections requiring use of antibiotic or antiviral drugs * non-ambulatory status * suspected drug or alcohol abuse
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Influenza-like Illness | 16 weeks | Number of subjects in each group meeting the definition of influenza-like illness during treatment (i.e. those subject reporting one or more moderate to severe cold/flu symptoms during the treatment period). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Impact of Cold/Flu Symptoms | 16 weeks | Number of subjects in each group reporting that cold/flu symptoms impacted the following 9 measures of daily life: ability to (1) think clearly, (2) sleep well, (3) breathe easily, (4) walk, climb stairs and exercise, (5) perform daily tasks, (6) work outside the home, (7) work inside the home, (8) interact with others, and (9) live personal life. |
| Symptom Incidence/Severity | 16 weeks | Number of subjects in each group reporting 13 different cold/flu symptoms assessed weekly |
| Negative Events Related to Cold/Flu Symptoms | 16 weeks | Number of subjects in each group reporting one or days of occurrence of the following 6 negative events: (1) felt sick, (2) missed work, (3) went to the doctor, (4) went to the pharmacy, (5) took cold/flu medication, and (6) skipped a planned activity |
| Incidence/Severity of Viral Respiratory Infections | 16 weeks | Number of subjects in each group with a confirmed viral respiratory infection and the proportion of subjects reporting a mild vs. moderate to severe infection |
Countries
Australia
Participant flow
Recruitment details
A total of 200 healthy volunteers were enrolled at the University of Western Australia in Perth between April 17 and July 31, 2009.
Pre-assignment details
Two of 200 randomized subjects (one in each group) decided not to begin study treatment after enrollment, so only 198 subjects were evaluable for response.
Participants by arm
| Arm | Count |
|---|---|
| Interferon-alpha 150 international units of interferon-alpha given once daily for 16 weeks in an orally disolving lozenge consisting of 200 mg of anhydrous crystalline maltose | 100 |
| Placebo 200 mg anhydrous crystalline maltose given once daily for 16 weeks in an orally disolving lozenge | 100 |
| Total | 200 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 4 |
| Overall Study | Lost to Follow-up | 3 | 4 |
| Overall Study | Protocol Violation | 4 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Placebo | Interferon-alpha | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 9 Participants | 5 Participants | 14 Participants |
| Age, Categorical Between 18 and 65 years | 91 Participants | 95 Participants | 186 Participants |
| Age Continuous | 47.3 years STANDARD_DEVIATION 13.2 | 45.0 years STANDARD_DEVIATION 14.4 | 46.2 years STANDARD_DEVIATION 14.2 |
| Region of Enrollment Australia | 100 participants | 100 participants | 200 participants |
| Sex: Female, Male Female | 66 Participants | 70 Participants | 136 Participants |
| Sex: Female, Male Male | 34 Participants | 30 Participants | 64 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 30 / 99 | 33 / 99 |
| serious Total, serious adverse events | 1 / 99 | 1 / 99 |
Outcome results
Primary
Frequency of Influenza-like Illness
Number of subjects in each group meeting the definition of influenza-like illness during treatment (i.e. those subject reporting one or more moderate to severe cold/flu symptoms during the treatment period).
Time frame: 16 weeks
Population: Intent-to-treat, defined as all randomized subjects who took at least one dose of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Interferon-alpha | Frequency of Influenza-like Illness | Age under 50 | 38 participants |
| Interferon-alpha | Frequency of Influenza-like Illness | Seasonal flu vaccine, no | 38 participants |
| Interferon-alpha | Frequency of Influenza-like Illness | Age 50 and over | 16 participants |
| Interferon-alpha | Frequency of Influenza-like Illness | Gender, Male | 11 participants |
| Interferon-alpha | Frequency of Influenza-like Illness | Seasonal flu vaccine, yes | 16 participants |
| Interferon-alpha | Frequency of Influenza-like Illness | Gender, Female | 43 participants |
| Interferon-alpha | Frequency of Influenza-like Illness | Overall | 54 participants |
| Placebo | Frequency of Influenza-like Illness | Gender, Female | 40 participants |
| Placebo | Frequency of Influenza-like Illness | Overall | 62 participants |
| Placebo | Frequency of Influenza-like Illness | Age 50 and over | 28 participants |
| Placebo | Frequency of Influenza-like Illness | Age under 50 | 34 participants |
| Placebo | Frequency of Influenza-like Illness | Seasonal flu vaccine, yes | 36 participants |
| Placebo | Frequency of Influenza-like Illness | Seasonal flu vaccine, no | 26 participants |
| Placebo | Frequency of Influenza-like Illness | Gender, Male | 22 participants |
p-value: 0.25Chi-squared
p-value: 0.01Chi-squared
p-value: 0.32Chi-squared
p-value: 0.01Chi-squared
p-value: 0.45Chi-squared
p-value: 0.03Chi-squared
p-value: 0.99Chi-squared
Secondary
Impact of Cold/Flu Symptoms
Number of subjects in each group reporting that cold/flu symptoms impacted the following 9 measures of daily life: ability to (1) think clearly, (2) sleep well, (3) breathe easily, (4) walk, climb stairs and exercise, (5) perform daily tasks, (6) work outside the home, (7) work inside the home, (8) interact with others, and (9) live personal life.
Time frame: 16 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Interferon-alpha | Impact of Cold/Flu Symptoms | sleep well | 54 participants |
| Interferon-alpha | Impact of Cold/Flu Symptoms | walk, climb stairs and exercise | 44 participants |
| Interferon-alpha | Impact of Cold/Flu Symptoms | work inside the home | 42 participants |
| Interferon-alpha | Impact of Cold/Flu Symptoms | perform daily activities | 46 participants |
| Interferon-alpha | Impact of Cold/Flu Symptoms | live personal life | 44 participants |
| Interferon-alpha | Impact of Cold/Flu Symptoms | work outside the home | 43 participants |
| Interferon-alpha | Impact of Cold/Flu Symptoms | think clearly | 53 participants |
| Interferon-alpha | Impact of Cold/Flu Symptoms | interact with others | 41 participants |
| Interferon-alpha | Impact of Cold/Flu Symptoms | breathe easily | 58 participants |
| Placebo | Impact of Cold/Flu Symptoms | live personal life | 51 participants |
| Placebo | Impact of Cold/Flu Symptoms | sleep well | 64 participants |
| Placebo | Impact of Cold/Flu Symptoms | work inside the home | 51 participants |
| Placebo | Impact of Cold/Flu Symptoms | interact with others | 50 participants |
| Placebo | Impact of Cold/Flu Symptoms | breathe easily | 61 participants |
| Placebo | Impact of Cold/Flu Symptoms | walk, climb stairs and exercise | 49 participants |
| Placebo | Impact of Cold/Flu Symptoms | perform daily activities | 54 participants |
| Placebo | Impact of Cold/Flu Symptoms | work outside the home | 51 participants |
| Placebo | Impact of Cold/Flu Symptoms | think clearly | 59 participants |
p-value: 0.2Chi-squared
p-value: 0.2Chi-squared
p-value: 0.39Chi-squared
p-value: 0.15Chi-squared
p-value: 0.66Chi-squared
p-value: 0.48Chi-squared
p-value: 0.26Chi-squared
p-value: 0.25Chi-squared
p-value: 0.32Chi-squared
Secondary
Incidence/Severity of Viral Respiratory Infections
Number of subjects in each group with a confirmed viral respiratory infection and the proportion of subjects reporting a mild vs. moderate to severe infection
Time frame: 16 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Interferon-alpha | Incidence/Severity of Viral Respiratory Infections | moderate/severe non-influenza infection | 4 participants |
| Interferon-alpha | Incidence/Severity of Viral Respiratory Infections | incidence of viral respiratory infection | 20 participants |
| Interferon-alpha | Incidence/Severity of Viral Respiratory Infections | moderate/severe viral respiratory infection | 5 participants |
| Interferon-alpha | Incidence/Severity of Viral Respiratory Infections | moderate/severe influenza infection | 1 participants |
| Placebo | Incidence/Severity of Viral Respiratory Infections | moderate/severe influenza infection | 4 participants |
| Placebo | Incidence/Severity of Viral Respiratory Infections | moderate/severe non-influenza infection | 11 participants |
| Placebo | Incidence/Severity of Viral Respiratory Infections | moderate/severe viral respiratory infection | 16 participants |
| Placebo | Incidence/Severity of Viral Respiratory Infections | incidence of viral respiratory infection | 23 participants |
p-value: 0.61Chi-squared
p-value: 0.003Chi-squared
p-value: 0.03Chi-squared
p-value: 0.03Chi-squared
Secondary
Negative Events Related to Cold/Flu Symptoms
Number of subjects in each group reporting one or days of occurrence of the following 6 negative events: (1) felt sick, (2) missed work, (3) went to the doctor, (4) went to the pharmacy, (5) took cold/flu medication, and (6) skipped a planned activity
Time frame: 16 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Interferon-alpha | Negative Events Related to Cold/Flu Symptoms | felt sick | 62 participants |
| Interferon-alpha | Negative Events Related to Cold/Flu Symptoms | missed work | 32 participants |
| Interferon-alpha | Negative Events Related to Cold/Flu Symptoms | visited the doctor | 16 participants |
| Interferon-alpha | Negative Events Related to Cold/Flu Symptoms | visited the pharmacy | 34 participants |
| Interferon-alpha | Negative Events Related to Cold/Flu Symptoms | took cold/flu medication | 57 participants |
| Interferon-alpha | Negative Events Related to Cold/Flu Symptoms | skipped a planned activity | 46 participants |
| Placebo | Negative Events Related to Cold/Flu Symptoms | took cold/flu medication | 65 participants |
| Placebo | Negative Events Related to Cold/Flu Symptoms | felt sick | 65 participants |
| Placebo | Negative Events Related to Cold/Flu Symptoms | visited the pharmacy | 30 participants |
| Placebo | Negative Events Related to Cold/Flu Symptoms | missed work | 33 participants |
| Placebo | Negative Events Related to Cold/Flu Symptoms | skipped a planned activity | 45 participants |
| Placebo | Negative Events Related to Cold/Flu Symptoms | visited the doctor | 16 participants |
p-value: 0.66Chi-squared
p-value: 0.88Chi-squared
p-value: 1Chi-squared
p-value: 0.54Chi-squared
p-value: 0.24Chi-squared
p-value: 0.89Chi-squared
Secondary
Symptom Incidence/Severity
Number of subjects in each group reporting 13 different cold/flu symptoms assessed weekly
Time frame: 16 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Interferon-alpha | Symptom Incidence/Severity | any cold/flu symptoms | 86 participants |
| Interferon-alpha | Symptom Incidence/Severity | moderate to severe feverishness | 12 participants |
| Interferon-alpha | Symptom Incidence/Severity | moderate to severe head congestion | 23 participants |
| Interferon-alpha | Symptom Incidence/Severity | moderate to severe sore throat | 27 participants |
| Placebo | Symptom Incidence/Severity | moderate to severe sore throat | 39 participants |
| Placebo | Symptom Incidence/Severity | any cold/flu symptoms | 92 participants |
| Placebo | Symptom Incidence/Severity | moderate to severe head congestion | 36 participants |
| Placebo | Symptom Incidence/Severity | moderate to severe feverishness | 24 participants |
p-value: 0.16Chi-squared
p-value: 0.03Chi-squared
p-value: 0.04Chi-squared
p-value: 0.07Chi-squared
Post Hoc
Acute Respiratory Illness
Number of subjects in each group meeting definition of acute respiratory illness (ARI), defined as 2 or more cold/flu symptoms reported in the same week. Further defined as febrile or afebrile depending on whether the subject reported the symptom of feverishness.
Time frame: 16 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Interferon-alpha | Acute Respiratory Illness | moderate/severe ARI | 41 participants |
| Interferon-alpha | Acute Respiratory Illness | moderate/severe febrile ARI | 12 participants |
| Interferon-alpha | Acute Respiratory Illness | moderate/severe afebrile ARI | 35 participants |
| Interferon-alpha | Acute Respiratory Illness | all acute respiratory illness (ARI) | 83 participants |
| Placebo | Acute Respiratory Illness | all acute respiratory illness (ARI) | 86 participants |
| Placebo | Acute Respiratory Illness | moderate/severe ARI | 54 participants |
| Placebo | Acute Respiratory Illness | moderate/severe afebrile ARI | 31 participants |
| Placebo | Acute Respiratory Illness | moderate/severe febrile ARI | 24 participants |
p-value: 0.54Chi-squared
p-value: 0.06Chi-squared
p-value: 0.03Chi-squared
p-value: 0.6Chi-squared