AF219-012 12-Week Study in Subjects with Refractory Chronic Cough
Research type
Research Study
Full title
A 12-Week Study to Assess the Efficacy and Tolerability of AF-219 in Subjects with Treatment Refractory Chronic Cough.
IRAS ID
192732
Contact name
Michael Kitt
Contact email
Sponsor organisation
Afferent Pharmaceuticals Inc
Eudract number
2015-005064-42
Clinicaltrials.gov Identifier
Research summary
Cough is a defence mechanism to clear the airways. Chronic cough is defined as cough lasting longer than 8 weeks. It is associated with significant morbidity. In some patients an identifiable cause (e.g. asthma, reflux disease) may be associated with the cough and treatment for the trigger may be beneficial. In other groups targeted treatment is ineffective, or investigations fail to identify any underlying cause. These groups suffer from refractory chronic cough. Over-sensitive airway nerves may be responsible for this currently untreatable condition.
P2X3 receptors are located on airway nerves. They can become sensitised by the action of adenosine triphosphate (ATP) when ATP is released by damaged, stressed or inflamed tissues. The investigative compound AF-219 has been shown to block P2X3 containing receptors sensitised by ATP and this action provides a rationale for use in refractory chronic cough.
The study design is randomised, placebo-controlled, double-blind and multicentre. There are 4 treatment groups (i) AF-219 7.5mg (ii) AF-219 20 mg; (iii) AF-219 50 mg and (iv) placebo. Treatment will be assigned in a random balanced sequence with a 3:1 ratio of AF-219 (active ingredient) to placebo (no active ingredient).
AF-219 and placebo tablets will look identical and be taken orally twice daily for 12 weeks. Neither subject nor study doctor will know the treatment allocation, thus the design is placebo controlled and double blind.
About 200 subjects will be recruited at hospitals with specialist cough clinics at approximately 10 UK centres (and some in the US).Effectiveness of AF-219 in reducing cough frequency will be measured (i) objectively by recording the number of coughs during awake hours and 24-hour periods on treatment days 0, 24, 56 and 84, using a sound recording device worn by subjects and (ii) subjectively utilising questionnaires on symptom severity and quality of life.
REC name
North East - Newcastle & North Tyneside 1 Research Ethics Committee
REC reference
16/NE/0014
Date of REC Opinion
26 Feb 2016
REC opinion
Further Information Favourable Opinion