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    Clinical Trial Results:
    A Phase 2a, Randomised, Double-blind, Placebo-controlled Assessment of the Safety and Protective Efficacy of Flufirvitide-3 (FF-3) Dry Powder Administered by Nasal Inhalation for 5 Days to Healthy Adult Subjects who are Experimentally Infected with a Challenge Strain of Influenza A Virus

    Summary
    EudraCT number
    		 2015-001103-31
    Trial protocol
    		 GB  
    Global end of trial date
    16 Jun 2016

    Results information
    Results version number
    		 v1(current)
    This version publication date
    07 Jun 2017
    First version publication date
    07 Jun 2017
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    AIT02-2001/DMID 14-0052
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02423577
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Autoimmune Technologies, LLC
    Sponsor organisation address
    830 Union Street, Suite 200, New Orleans, Louisiana, United States, 70112
    Public contact
    Russell B. Wilson, PhD, Autoimmune Technologies, LLC, +1 504-896-2789,
    Scientific contact
    Russell B. Wilson, PhD, Autoimmune Technologies, LLC, +1 504-896-2789,
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    16 Jun 2016
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    16 Jun 2016
    Global end of trial reached?
    Yes
    Global end of trial date
    16 Jun 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To determine the effect of prophylaxis with FF-3 (i.e. protective efficacy) in comparison to placebo on the frequencies of viral shedding, infectivity, and sero-conversion in subjects who are experimentally inoculated with a live, wild-type A/California/H1N1 2009 challenge strain of influenza A virus.
    Protection of trial subjects
    The study was conducted in accordance with Good Clinical Practice as required by the International Council on Harmonization guidelines and in accordance with the ethical principles of the Declaration of Helsinki.
    Background therapy
    		 Subjects received live, wild-type A/California/H1N1 2009 challenge strain of influenza A virus. The challenge virus was administered by intranasal inoculation approximately 4 hours after the subject had received their first dose of either FF-3 or placebo.
    Evidence for comparator
    		 -
    Actual start date of recruitment
    14 Sep 2015
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Kingdom: 79
    Worldwide total number of subjects
    79
    EEA total number of subjects
    79
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    79
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 79 healthy adults were recruited into the single-site study, between 14 September 2015 and 16 June 2016. Following screening, subjects were randomised in 1 of 2 groups using a ratio of 2:1 (FF-3:placebo). All subjects received training in the appropriate use of the Early Phase I Clinical (EPIC) dry powder inhaler prior to dosing.

    Pre-assignment
    Screening details
    		 Potential subjects were screened to determine their susceptibility to infection with the challenge strain as indicated by a serum antibody titre less than 1:10. Only subjects susceptible to the challenge strain qualified for study specific screening.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Carer
    Blinding implementation details
    All subjects and staff members responsible for administering the treatment to the subjects and all other aspects of study management remained blinded, unless unblinding was necessary for safety reasons.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 FF-3
    Arm description
    		 FF-3 dry powder was administered as a nasal inhalation aerosol with the EPIC dry powder inhaler. Subjects were dosed twice daily (approximately 12 hours apart) for 5 days and a single dose on the morning of Day 6 at a dose of 9 milligrams (mg). The total daily dose of FF-3 was 18 mg and subjects received a total of 11 doses. The first dose of FF-3 was administered approximately 4 hours before the challenge virus. A single dose of challenge virus (influenza A/California/H1N1/2009) was administered by intranasal administration in a total volume of 0.5 millilitres (mL) (0.25 mL per nostril). A second dose of FF-3 was administered approximately 4 hours after nasal inoculation with the challenge virus.
    Arm type
    		 Experimental

    Investigational medicinal product name
    FF-3
    Investigational medicinal product code
    Other name
    Flufirvitide-3
    Pharmaceutical forms
    Inhalation powder, pre-dispensed
    Routes of administration
    Nasal use
    Dosage and administration details
    FF-3 was provided in unit dose blisters containing 4.5 mg of FF-3 in a powder formulation for administration as nasal inhalation aerosol with the EPIC dry powder inhaler. The EPIC dry powder inhaler is a single-dose, breath-activated device that delivers a powder formulation. In addition to 4.5 mg FF-3, each contained dibasic potassium phosphate, trehalose, and monobasic potassium phosphate.

    Arm title
    		 Placebo
    Arm description
    		 A matching placebo was administered as a nasal inhalation aerosol with the EPIC dry powder inhaler twice daily (approximately 12 hours apart) for five days and a single dose on morning of Day 6. Subjects received a total of 11 doses. The first dose of placebo was administered approximately 4 hours before the challenge virus. A single dose of challenge virus (influenza A/California/H1N1/2009) was administered by intranasal administration in a total volume of 0.5 mL (0.25 mL per nostril). A second dose of placebo was administered approximately 4 hours after nasal inoculation with the challenge virus.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation powder, pre-dispensed
    Routes of administration
    Nasal use
    Dosage and administration details
    Placebo was provided in unit dose blisters, which matched the appearance of the FF-3 blister packs for nasal inhalation as nasal inhalation aerosol with the EPIC dry powder inhaler. Each blister contained monobasic potassium phosphate, dibasic potassium phosphate, and trehalose.

    Number of subjects in period 1
    		FF-3 Placebo
    Started
    53
    26
    Completed
    53
    26

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    FF-3
    Reporting group description
    		 FF-3 dry powder was administered as a nasal inhalation aerosol with the EPIC dry powder inhaler. Subjects were dosed twice daily (approximately 12 hours apart) for 5 days and a single dose on the morning of Day 6 at a dose of 9 milligrams (mg). The total daily dose of FF-3 was 18 mg and subjects received a total of 11 doses. The first dose of FF-3 was administered approximately 4 hours before the challenge virus. A single dose of challenge virus (influenza A/California/H1N1/2009) was administered by intranasal administration in a total volume of 0.5 millilitres (mL) (0.25 mL per nostril). A second dose of FF-3 was administered approximately 4 hours after nasal inoculation with the challenge virus.

    Reporting group title
    Placebo
    Reporting group description
    		 A matching placebo was administered as a nasal inhalation aerosol with the EPIC dry powder inhaler twice daily (approximately 12 hours apart) for five days and a single dose on morning of Day 6. Subjects received a total of 11 doses. The first dose of placebo was administered approximately 4 hours before the challenge virus. A single dose of challenge virus (influenza A/California/H1N1/2009) was administered by intranasal administration in a total volume of 0.5 mL (0.25 mL per nostril). A second dose of placebo was administered approximately 4 hours after nasal inoculation with the challenge virus.

    Reporting group values
    		 FF-3 Placebo Total
    Number of subjects
    		 53 26
    Age categorical
    Units: Subjects
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 31.7 ( 8.5 ) 32.7 ( 9.3 ) -
    Gender Categorical
    Units: Subjects
        Male
    		 40 14 54
        Female
    		 13 12 25

    End points

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    End points reporting groups
    Reporting group title
    FF-3
    Reporting group description
    		 FF-3 dry powder was administered as a nasal inhalation aerosol with the EPIC dry powder inhaler. Subjects were dosed twice daily (approximately 12 hours apart) for 5 days and a single dose on the morning of Day 6 at a dose of 9 milligrams (mg). The total daily dose of FF-3 was 18 mg and subjects received a total of 11 doses. The first dose of FF-3 was administered approximately 4 hours before the challenge virus. A single dose of challenge virus (influenza A/California/H1N1/2009) was administered by intranasal administration in a total volume of 0.5 millilitres (mL) (0.25 mL per nostril). A second dose of FF-3 was administered approximately 4 hours after nasal inoculation with the challenge virus.

    Reporting group title
    Placebo
    Reporting group description
    		 A matching placebo was administered as a nasal inhalation aerosol with the EPIC dry powder inhaler twice daily (approximately 12 hours apart) for five days and a single dose on morning of Day 6. Subjects received a total of 11 doses. The first dose of placebo was administered approximately 4 hours before the challenge virus. A single dose of challenge virus (influenza A/California/H1N1/2009) was administered by intranasal administration in a total volume of 0.5 mL (0.25 mL per nostril). A second dose of placebo was administered approximately 4 hours after nasal inoculation with the challenge virus.

    Primary: Percentage of Subjects Demonstrating Viral Shedding.

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    End point title
    		 Percentage of Subjects Demonstrating Viral Shedding.
    End point description
    Nasal washes were collected from all subjects to assess the magnitude and duration of viral shedding before the virus inoculation and once daily on Day 2 through Day 10. Evidence of viral shedding was defined as a positive real time reverse transcription polymerase chain reaction (RT-PCR) result for the challenge virus obtained on at least one post inoculation day in the time interval beginning on Day 2 and ending on the completion of the inpatient observation period on Day 10. The percentage of subjects demonstrating viral shedding was estimated for each treatment with corresponding asymptotic 95% confidence intervals, based on the normal approximation to the binomial distribution (Wilsons’s method).
    End point type
    Primary
    End point timeframe
    Day 2-Day 10
    End point values
    		 FF-3 Placebo
    Number of subjects analysed
    53
    26
    Units: percentage of Subjects
        number (confidence interval 95%)
    96.2 (87.2 to 99)
    84.6 (66.5 to 93.8)
    Statistical analysis title
    		 Comparison of Relative Risk
    Comparison groups
    Placebo v FF-3
    Number of subjects included in analysis
    79
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    P-value
    		 = 0.1436 [2]
    Method
    		 Chi-squared
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.14
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.98
         upper limit
    		 1.31
    Notes
    [1] - This study is powered to 80% to detect a 2- to 3-fold reduction in infectivity due to FF-3 treatment.
    [2] - P-value is based on the normal approximation for the ratio of binomial distributions on the log scale. Significance level = 10%.

    Primary: Percentage of Subjects Demonstrating Viral Infection.

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    End point title
    		 Percentage of Subjects Demonstrating Viral Infection.
    End point description
    Nasal washes were collected from all subjects to assess infection rate, before the virus inoculation and once daily, on Day 2 through Day 10. Evidence of infectivity was defined as a positive tissue culture result (median tissue culture infective dose [TCID50]) for the challenge virus obtained on at least one post inoculation day in the time interval beginning on Day 2 and ending on the completion of the inpatient observation period on Day 10. The percentage of subjects demonstrating viral infection was estimated for each treatment with corresponding asymptotic 95% confidence intervals, based on the normal approximation to the binomial distribution (Wilsons’s method).
    End point type
    Primary
    End point timeframe
    Day 2-Day 10
    End point values
    		 FF-3 Placebo
    Number of subjects analysed
    53
    26
    Units: percentage of subjects
        number (confidence interval 95%)
    69.8 (56.5 to 80.5)
    73.1 (53.9 to 86.3)
    Statistical analysis title
    		 Comparison of Relative Risk
    Comparison groups
    FF-3 v Placebo
    Number of subjects included in analysis
    79
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [3]
    P-value
    		 = 0.7596 [4]
    Method
    		 Chi-squared
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    0.96
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.75
         upper limit
    		 1.22
    Notes
    [3] - This study is powered to 80% to detect a 2- to 3-fold reduction in infectivity due to FF-3 treatment.
    [4] - P-value is based on the normal approximation for the ratio of binomial distributions on the log scale. Significance level = 10%

    Primary: Percentage of Subjects Demonstrating Sero-Conversion.

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    End point title
    		 Percentage of Subjects Demonstrating Sero-Conversion.
    End point description
    Evidence of sero-conversion against the challenge virus is defined as a 4-fold or greater rise in serum Haemagglutinin inhibition (HAI) antibody titre between subject serum samples obtained at check-in on Study Day -2 and at the post-treatment follow-up on Study Day 30. The percentage of subjects demonstrating sero-conversion at Day 30 was estimated for each treatment with corresponding asymptotic 95% confidence intervals, based on the normal approximation to the binomial distribution (Wilsons’s method).
    End point type
    Primary
    End point timeframe
    Day 30
    End point values
    		 FF-3 Placebo
    Number of subjects analysed
    53
    26
    Units: percentage of subjects
        number (confidence interval 95%)
    73.6 (60.4 to 83.6)
    65.4 (46.2 to 80.6)
    Statistical analysis title
    		 Comparison of Relative Risk
    Comparison groups
    FF-3 v Placebo
    Number of subjects included in analysis
    79
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [5]
    P-value
    		 = 0.4732 [6]
    Method
    		 Chi-squared
    Parameter type
    		 Risk ratio (RR)
    Point estimate
    1.13
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.86
         upper limit
    		 1.48
    Notes
    [5] - This study is powered to 80% to detect a 2- to 3-fold reduction in infectivity due to FF-3 treatment.
    [6] - P-value is based on the normal approximation for the ratio of binomial distributions on the log scale. Significance level = 10%.

    Secondary: Mean Physician and Subject-Reported Influenza Total Sign/Symptom Scores (TSS).

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    End point title
    		 Mean Physician and Subject-Reported Influenza Total Sign/Symptom Scores (TSS).
    End point description
    From Day 1 to Day 10, investigators evaluated 4 signs of illness including fever, nasal discharge, pharyngitis, and new wheezes, rales, or rhonchi on lung auscultation. Subjects also self-evaluated 16 signs and symptoms of illness including nasal stuffiness/congestion, runny nose, sore throat, sneezing, hoarseness, earache, facial or eye pain/tenderness, cough, wheezy chest, breathing difficulty, musculoskeletal ache, nausea/vomiting, feeling hot/feverishness/chills/rigor, headache, fatigue, diarrhoea. All reported symptoms were graded on a 4-point scale: 0-Absent, 1-Mild, 2-Moderate and 3-Severe. The TSS was calculated for each subject as the mean of 1 or 2 replicate assessments per day of the total symptom count for the 4 physician-reported signs and symptoms and 16 subject-reported symptoms. The overall mean TSS from Day 1 to Day 10 was recorded for both physician and subject-reported influenza symptoms.
    End point type
    Secondary
    End point timeframe
    Day 1-Day 10
    End point values
    		 FF-3 Placebo
    Number of subjects analysed
    53
    26
    Units: units on a scale
    arithmetic mean (confidence interval 95%)
        Overall Physician-Reported TSS
    0.11 (0.07 to 0.15)
    0.08 (0.04 to 0.12)
        Overall Subject-Reported TSS
    0.8 (0.58 to 1.02)
    0.89 (0.51 to 1.27)
    Statistical analysis title
    		 Comparison of Physician-Reported TSS
    Comparison groups
    FF-3 v Placebo
    Number of subjects included in analysis
    79
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.3493 [7]
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.03
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -0.02
         upper limit
    		 0.08
    Notes
    [7] - Significance level = 10%.
    Statistical analysis title
    		 Comparison of Subject-Reported TSS
    Comparison groups
    FF-3 v Placebo
    Number of subjects included in analysis
    79
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.664 [8]
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.09
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -0.43
         upper limit
    		 0.25
    Notes
    [8] - Significance level = 10%.

    Secondary: Mean Levels of Pro-inflammatory and Antiviral Cytokines.

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    End point title
    		 Mean Levels of Pro-inflammatory and Antiviral Cytokines.
    End point description
    Nasal washes were collected from all subjects once daily, on Day 1 through Day 10 to measure pro-inflammatory and antiviral cytokine concentrations (Interleukin 6, Tumour Necrosis Factor (TNF) alpha, interferon alpha, and interferon gamma). The pro-inflammatory and antiviral cytokine assay results were corrected for sampling dilution inconsistencies by normalising to their corresponding urea nitrogen concentrations. Mean pro-inflammatory and antiviral cytokine concentrations were calculated as the area under the curve (AUC)/time on the log10 scale over Days 1 to 10 for subjects with at least 50% of planned measurements collected. All AUC were calculated using the linear trapezoidal method.
    End point type
    Secondary
    End point timeframe
    Day 1-Day 10
    End point values
    		 FF-3 Placebo
    Number of subjects analysed
    53
    26
    Units: picograms (pg)/mL
    arithmetic mean (confidence interval 95%)
        Mean Interleukin 6
    2.327 (2.161 to 2.493)
    2.253 (2.01 to 2.496)
        Mean TNF-Alpha
    1.581 (1.484 to 1.677)
    1.452 (1.316 to 1.588)
        Mean Interferon-Alpha
    2.56 (2.5 to 2.62)
    2.53 (2.41 to 2.64)
        Mean Interferon-Gamma
    1.122 (0.988 to 1.256)
    1.067 (0.857 to 1.276)
    Statistical analysis title
    		 Interleukin 6 Comparison
    Comparison groups
    FF-3 v Placebo
    Number of subjects included in analysis
    79
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.6099 [9]
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.074
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -0.166
         upper limit
    		 0.314
    Notes
    [9] - Significance level = 10%.
    Statistical analysis title
    		 TNF-Alpha Comparison
    Comparison groups
    FF-3 v Placebo
    Number of subjects included in analysis
    79
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1242 [10]
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.129
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -0.009
         upper limit
    		 0.267
    Notes
    [10] - Significance level = 10%.
    Statistical analysis title
    		 Interferon-Alpha Comparison
    Comparison groups
    FF-3 v Placebo
    Number of subjects included in analysis
    79
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.6056 [11]
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.03
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -0.07
         upper limit
    		 0.12
    Notes
    [11] - Significance level = 10%.
    Statistical analysis title
    		 Interferon-Gamma Comparison
    Comparison groups
    FF-3 v Placebo
    Number of subjects included in analysis
    79
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.6423 [12]
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.056
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -0.143
         upper limit
    		 0.254
    Notes
    [12] - Significance level = 10%.

    Secondary: Mean Viral Load.

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    End point title
    		 Mean Viral Load.
    End point description
    Nasal washes were collected from all subjects to assess viral load once daily on Day 1 through Day 10. Mean viral load was calculated as AUC/time on the log10 scale for both the RT-PCR and TCID50 methods over Days 1 to 10 for subjects with at least 50% of planned measurements collected. All AUC were calculated using the linear trapezoidal method.
    End point type
    Secondary
    End point timeframe
    Day 1-Day 10
    End point values
    		 FF-3 Placebo
    Number of subjects analysed
    53
    26
    Units: copies/mL
    arithmetic mean (confidence interval 95%)
        Mean RT-PCR
    2.918 (2.376 to 3.46)
    2.877 (2.086 to 3.668)
        Mean TCID50
    1.528 (1.338 to 1.719)
    1.441 (1.177 to 1.706)
    Statistical analysis title
    		 TCID50 Viral Load Comparison
    Comparison groups
    FF-3 v Placebo
    Number of subjects included in analysis
    79
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.5928 [13]
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.087
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -0.183
         upper limit
    		 0.358
    Notes
    [13] - Significance level = 10%.
    Statistical analysis title
    		 RT-PCR Viral Load Comparsion
    Comparison groups
    FF-3 v Placebo
    Number of subjects included in analysis
    79
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.9311 [14]
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.041
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -0.742
         upper limit
    		 0.824
    Notes
    [14] - Significance level = 10%.

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to Day 30 (+/- 3 days).
    Adverse event reporting additional description
    A treatment-emergent adverse event (TEAE) was defined as an adverse event which occurred after the start of dosing or which was present pre-dose and became more severe after the start of dosing. The Safety analysis set included all subjects who received at least one dose of treatment (FF-3 or placebo).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    18.1
    Reporting groups
    Reporting group title
    FF-3
    Reporting group description
    		 FF-3 dry powder was administered as a nasal inhalation aerosol with the EPIC dry powder inhaler twice daily (approximately 12 hours apart) for 5 days and a single dose on the morning of Day 6 at a dose of 9 milligrams (mg). The total daily dose of FF-3 was 18 mg and subjects received a total of 11 doses. The first dose of FF-3 was administered approximately 4 hours before the challenge virus. A single dose of challenge virus (influenza A/California/H1N1/2009) was administered by intranasal administration in a total volume of 0.5 millilitres (mL) (0.25 mL per nostril). A second dose of FF-3 was administered approximately 4 hours after the nasal inoculation with challenge virus.

    Reporting group title
    Placebo
    Reporting group description
    		 A matching placebo was administered as a nasal inhalation aerosol with the EPIC dry powder inhaler twice daily (approximately 12 hours apart) for five days and a single dose on morning of Day 6. Subjects received a total of 11 doses. The first dose of placebo was administered approximately 4 hours before the challenge virus. A single dose of challenge virus (influenza A/California/H1N1/2009) was administered by intranasal administration in a total volume of 0.5 mL (0.25 mL per nostril). A second dose of placebo was administered approximately 4 hours after the nasal inoculation with challenge virus.

    Serious adverse events
    		 FF-3 Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 53 (0.00%)
    0 / 26 (0.00%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 FF-3 Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    46 / 53 (86.79%)
    23 / 26 (88.46%)
    Injury, poisoning and procedural complications
    Limb Injury
         subjects affected / exposed
    1 / 53 (1.89%)
    0 / 26 (0.00%)
         occurrences all number
    2
    0
    Accidental Exposure To Product
         subjects affected / exposed
    0 / 53 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Musculoskeletal Injury
         subjects affected / exposed
    0 / 53 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    5 / 53 (9.43%)
    1 / 26 (3.85%)
         occurrences all number
    5
    1
    Lethargy
         subjects affected / exposed
    2 / 53 (3.77%)
    0 / 26 (0.00%)
         occurrences all number
    2
    0
    Dysgeusia
         subjects affected / exposed
    1 / 53 (1.89%)
    2 / 26 (7.69%)
         occurrences all number
    1
    2
    Restless Legs Syndrome
         subjects affected / exposed
    0 / 53 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    General disorders and administration site conditions
    Influenza Like Illness
         subjects affected / exposed
    34 / 53 (64.15%)
    14 / 26 (53.85%)
         occurrences all number
    36
    14
    Fatigue
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 26 (3.85%)
         occurrences all number
    1
    1
    Vessel Puncture Site Haematoma
         subjects affected / exposed
    1 / 53 (1.89%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Feeling Hot
         subjects affected / exposed
    0 / 53 (0.00%)
    3 / 26 (11.54%)
         occurrences all number
    0
    3
    Medical Device Site Rash
         subjects affected / exposed
    0 / 53 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Eye disorders
    Eye Pain
         subjects affected / exposed
    1 / 53 (1.89%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    2 / 53 (3.77%)
    3 / 26 (11.54%)
         occurrences all number
    2
    3
    Diarrhoea
         subjects affected / exposed
    1 / 53 (1.89%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Nasal Congestion
         subjects affected / exposed
    5 / 53 (9.43%)
    6 / 26 (23.08%)
         occurrences all number
    5
    6
    Oropharyngeal Pain
         subjects affected / exposed
    5 / 53 (9.43%)
    7 / 26 (26.92%)
         occurrences all number
    6
    8
    Rhinorrhoea
         subjects affected / exposed
    5 / 53 (9.43%)
    0 / 26 (0.00%)
         occurrences all number
    5
    0
    Cough
         subjects affected / exposed
    2 / 53 (3.77%)
    1 / 26 (3.85%)
         occurrences all number
    2
    2
    Nasal Discomfort
         subjects affected / exposed
    2 / 53 (3.77%)
    0 / 26 (0.00%)
         occurrences all number
    2
    0
    Dyspnoea
         subjects affected / exposed
    1 / 53 (1.89%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Epistaxis
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 26 (3.85%)
         occurrences all number
    1
    1
    Wheezing
         subjects affected / exposed
    1 / 53 (1.89%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Sneezing
         subjects affected / exposed
    0 / 53 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    2
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    2 / 53 (3.77%)
    0 / 26 (0.00%)
         occurrences all number
    2
    0
    Pruritus
         subjects affected / exposed
    1 / 53 (1.89%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal and connective tissue disorders
    Back Pain
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 26 (3.85%)
         occurrences all number
    1
    1
    Pain In Extremity
         subjects affected / exposed
    1 / 53 (1.89%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Myalgia
         subjects affected / exposed
    0 / 53 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Paraesthesia
         subjects affected / exposed
    0 / 53 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Infections and infestations
    Otitis Media
         subjects affected / exposed
    1 / 53 (1.89%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Conjunctivitis
         subjects affected / exposed
    0 / 53 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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