Clinical Trial Results:
Effect of the CRTH2 antagonist OC459 on the response to rhinovirus challenge in asthma
Summary
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EudraCT number |
2015-002555-10 |
Trial protocol |
GB |
Global end of trial date |
24 Jan 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
13 Nov 2019
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First version publication date |
13 Nov 2019
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
ORCA2015
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02660489 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Imperial College
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Sponsor organisation address |
St Mary's Medical School Building, Norfolk Place, London, United Kingdom, W2 1PG
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Public contact |
Professor Sebastian Johnston, Imperial College, +44 20 7594 3849, s.johnston@imperial.ac.uk
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Scientific contact |
Professor Sebastian Johnston, Imperial College, +44 20 7594 3849, s.johnston@imperial.ac.uk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
22 Aug 2019
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
24 Jan 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
24 Jan 2018
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The overall aim of this study is to assess the effectiveness of the study drug (OC459) in preventing or attenuating the worsening of asthma symptoms (an asthma exacerbation) that occurs when asthma sufferers catch a cold (defined as an infection with the virus rhinovirus). The study drug will be compared with a placebo to find out the extent of any improvement in the condition of the participants. A placebo is a medically noneffective copy of the drug being tested; it looks and tastes the same as the treatment drug (it can be seen as a dummy drug).
In healthy subjects, rhinovirus infection causes symptoms of a cold e.g. sneezing, runny nose. In patients with asthma, rhinovirus infection causes a worsening of their asthma symptoms (e.g. breathlessness, wheeze) because of the way the immune system reacts to the virus. The study drug OC459 blocks activation of receptor cells found in the immune system and by blocking that activation may prevent an exacerbation of symptoms.
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Protection of trial subjects |
There were 11 scheduled visits for trial subjects, with seven of these scheduled during the period when subjects had a cold.
In addition subjects had access to the study team via mobile and email 24/7.
A procedure for unblinding was also available 24/7.
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Background therapy |
Subjects were told to continue their usual medication as prescribed. This included inhaled corticosteriods ('preventers') and inhaled short-acting beta agonists ('relievers'). | ||
Evidence for comparator |
A placebo was given in the comparator arm. | ||
Actual start date of recruitment |
18 Jan 2016
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 44
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Worldwide total number of subjects |
44
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EEA total number of subjects |
44
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
44
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Recruitment ran from 18 January 2016 until completion (November 2018; the last subjects were enrolled on 15 November 2018). This was a single site study. | |||||||||||||||||||||
Pre-assignment
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Screening details |
Volunteers who were potentially eligible for inclusion were screened by an Asthma Control Questionnaire, skin prick test, bronchoprovocation testing (using histamine) and rhinovirus serology (looking for evidence of antibodies to rhinovirus serotype 16). | |||||||||||||||||||||
Period 1
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Period 1 title |
Randomisation
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Is this the baseline period? |
No | |||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Assessor | |||||||||||||||||||||
Blinding implementation details |
The unblinded randomisation list was generated by a statistician working independently of the trial and entered into the study database. The unblinded randomisation list was also provided to the drug manufacturer in order to label the drug/placebo appropriately prior to dispensing to pharmacy. In this way the subjects, investigators, pharmacy, trial statisticians and study monitors were all blinded.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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OC459 | |||||||||||||||||||||
Arm description |
Subjects randomised to treatment with OC459 50mg once daily. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
OC459
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Investigational medicinal product code |
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Other name |
Timapiprant
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
50mg once daily for five weeks
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Arm title
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Placebo | |||||||||||||||||||||
Arm description |
Subjects randomised to treatment with placebo once daily. | |||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
One tablet once daily for five weeks
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Period 2
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Period 2 title |
Rhinovirus infection
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Is this the baseline period? |
Yes [1] | |||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Assessor | |||||||||||||||||||||
Blinding implementation details |
(as per previous period)
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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OC459 - confirmed rhinovirus infection | |||||||||||||||||||||
Arm description |
Subjects randomised to treatment with OC459 in whom infection with rhinovirus-16 was confirmed. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
OC459
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Investigational medicinal product code |
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Other name |
Timapiprant
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
50mg once daily for five weeks
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Arm title
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Placebo - confirmed rhinovirus infection | |||||||||||||||||||||
Arm description |
Subjects randomised to treatment with placebo in whom infection with rhinovirus-16 was confirmed. | |||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
One tablet once daily for five weeks
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Notes [1] - Period 1 is not the baseline period. It is expected that period 1 will be the baseline period. Justification: As per the Protocol and Statistical Analysis Plan, the full analysis set includes only subjects who have been randomised and in addition have confirmed rhinovirus-16 infection and completed at least 14 days post inoculation with rhinovirus-16. The baseline characteristics are provided for the Full Analysis Set, not the subjects enrolled, given the outcome analyses are performed on the Full Analysis Set. |
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Notes [2] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: As per the Protocol and Statistical Analysis Plan, the full analysis set includes only subjects who have been randomised and in addition have confirmed rhinovirus-16 infection and completed at least 14 days post inoculation with rhinovirus-16. [3] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period. Justification: As per the Protocol and Statistical Analysis Plan, the full analysis set includes only subjects who have been randomised and in addition have confirmed rhinovirus-16 infection and completed at least 14 days post inoculation with rhinovirus-16. |
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Baseline characteristics reporting groups
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Reporting group title |
OC459 - confirmed rhinovirus infection
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Reporting group description |
Subjects randomised to treatment with OC459 in whom infection with rhinovirus-16 was confirmed. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo - confirmed rhinovirus infection
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Reporting group description |
Subjects randomised to treatment with placebo in whom infection with rhinovirus-16 was confirmed. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
OC459
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Reporting group description |
Subjects randomised to treatment with OC459 50mg once daily. | ||
Reporting group title |
Placebo
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Reporting group description |
Subjects randomised to treatment with placebo once daily. | ||
Reporting group title |
OC459 - confirmed rhinovirus infection
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Reporting group description |
Subjects randomised to treatment with OC459 in whom infection with rhinovirus-16 was confirmed. | ||
Reporting group title |
Placebo - confirmed rhinovirus infection
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Reporting group description |
Subjects randomised to treatment with placebo in whom infection with rhinovirus-16 was confirmed. |
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End point title |
Total Lower Respiratory Symptom score | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Sum of daily scores for 14 days after rhinovirus inoculation
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Statistical analysis title |
Mann-Whitney test | ||||||||||||
Comparison groups |
OC459 - confirmed rhinovirus infection v Placebo - confirmed rhinovirus infection
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Number of subjects included in analysis |
30
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.78 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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End point title |
Asthma Control Questionnaire (ACQ)-6 score | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Change from baseline (rhinovirus inoculation, day 0) to day 10
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Statistical analysis title |
Unpaired T-test | ||||||||||||
Comparison groups |
OC459 - confirmed rhinovirus infection v Placebo - confirmed rhinovirus infection
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Number of subjects included in analysis |
30
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.49 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
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End point title |
Peak Expiratory Flow Rate | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Percentage change from baseline (rhinovirus inoculation, day 0) to trough during infection (up to day 14)
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Statistical analysis title |
Unpaired T-test | ||||||||||||
Comparison groups |
OC459 - confirmed rhinovirus infection v Placebo - confirmed rhinovirus infection
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Number of subjects included in analysis |
30
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.5 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
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End point title |
Forced Expiratory Volume in 1 Second (FEV1) | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Percentage change from baseline (rhinovirus inoculation, day 0) to trough during infection (up to day 14)
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Statistical analysis title |
Unpaired T-test | ||||||||||||
Comparison groups |
OC459 - confirmed rhinovirus infection v Placebo - confirmed rhinovirus infection
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Number of subjects included in analysis |
30
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.36 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
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End point title |
Exhaled nitric oxide (FeNO) | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Percentage change from baseline (rhinovirus inoculation, day 0) to peak during infection (measured on days 3, 5, 7, 10 post inoculation)
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Statistical analysis title |
Mann-Whitney test | ||||||||||||
Comparison groups |
Placebo - confirmed rhinovirus infection v OC459 - confirmed rhinovirus infection
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Number of subjects included in analysis |
30
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.12 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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End point title |
Airway Hyperresponsiveness (Assessed as the Provocation Concentration of Histamine Producing a 20% Fall in FEV1, or PC20) | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Change from baseline (rhinovirus inoculation, day 0) to day 7
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Notes [1] - One subject could not complete one of the two measurements owing to logistical issues. [2] - One subject could not complete one of the two measurements owing to logistical issues. |
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Statistical analysis title |
Mann-Whitney test | ||||||||||||
Comparison groups |
OC459 - confirmed rhinovirus infection v Placebo - confirmed rhinovirus infection
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Number of subjects included in analysis |
28
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.12 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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End point title |
Viral Load (in Nasal Lavage Samples) | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Peak during infection (up to day 14)
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Statistical analysis title |
Mann-Whitney test | ||||||||||||
Comparison groups |
OC459 - confirmed rhinovirus infection v Placebo - confirmed rhinovirus infection
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Number of subjects included in analysis |
30
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.75 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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End point title |
Total Upper Respiratory Symptom Score | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Sum of daily scores for 14 days after rhinovirus inoculation
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Statistical analysis title |
Mann-Whitney test | ||||||||||||
Comparison groups |
OC459 - confirmed rhinovirus infection v Placebo - confirmed rhinovirus infection
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Number of subjects included in analysis |
30
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.66 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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Adverse events information
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Timeframe for reporting adverse events |
Nine weeks' study duration, including the first five weeks during which subjects were treated with OC459/placebo.
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Assessment type |
Systematic | |||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
none used | |||||||||||||||||||||
Dictionary version |
n/a
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Reporting groups
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Reporting group title |
OC459
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Reporting group description |
All subjects randomised to OC459 | |||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
All subjects randomised to placebo | |||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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17 Jan 2017 |
Increase in recruitment target owing to lower infection rate and higher number of drop outs than anticipated. |
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11 Jul 2017 |
Increase in recruitment target as subjects enrolled had fewer asthma symptoms than anticipated. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |