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
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
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
|
|
||||||||||
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.
|
|||||||||
|
|
|||||||||||||||||||||||||||||||||||||||||||||
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. | ||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
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. |
|
|||||||||||||
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
|
||||||||||||
|
|||||||||||||
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%. |
|
|||||||||||||
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
|
||||||||||||
|
|||||||||||||
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% |
|
|||||||||||||
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
|
||||||||||||
|
|||||||||||||
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%. |
|
|||||||||||||||||||
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
|
||||||||||||||||||
|
|||||||||||||||||||
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%. |
|
|||||||||||||||||||||||||
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
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
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%. |
|
|||||||||||||||||||
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
|
||||||||||||||||||
|
|||||||||||||||||||
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 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
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 |