Clinical Trial: Ilaris (Canakinumab) in Patient With Periodic Fever, Aphthous Stomatitis, Pharyngitis and Cervical Adenitis (PFAPA)

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: Ilaris (Canakinumab) in Patient With Periodic Fever, Aphthous Stomatitis, Pharyngitis and Cervical Adenitis (PFAPA)

Brief Summary:

Periodic Fever, Aphthous stomatitis, Pharyngitis and cervical Adenitis (PFAPA) is one of the most common, least explored periodic fever syndrome in childhood. This study aims to investigate whether a single dose of an interleukin beta (IL-1) antagonist, Canakinumab will be able to abort PFAPA flares in patients who experience a flare in an average of 2 weeks or less. This will be a single arm open label pilot study. 10 patients will be recruited from 1 center (Pediatric rheumatology unit -Schneider children's medical center of Israel).

Patients in ages 2-10 years old who are diagnosed with PFAPA according to clinical criteria at least 3 months prior to enrollment and who are under regular care for this disease (single dose of glucocorticoids during flare) and who suffer from more than 4 PFAPA flares for the last 2 months, will be screened for this study. In the second documented flare, patients will be enrolled to receive a single dose of subcutaneous (SC) Canakinumab 4 mg/kg. The primary outcome is defined as - 50% reduction in PFAPA flares for the next 2 consecutive months as reported by the patient (use of diary) and documented by the patient primary care physician and/ or the researcher in a monthly follow up visits. Secondary outcome measure are define as time to flare (days) and Parent/patient quality of life assessment measured by 100mm visual analog scale (VAS).

Detailed Summary:

Study Objectives:

Primary objective: Patients will experience at least 50% reduction in PFAPA flares for the next 2 consecutive months after receiving single dose of canakinumab (4 mg/kg).

Secondary objectives:

1. Time to flare
2. Parent/patient quality of life assessment

Study rationale:

Periodic Fever, Aphthous stomatitis, Pharyngitis and cervical Adenitis (PFAPA) is one of the most common, least explored periodic fever syndrome in childhood. It was discovered only in 1987 by Marshall et al. who noticed periodic attacks of fever along with pharyngitis and cervical adenitis mimicking streptococcal acute tonsillitis. Many of these patients were erroneously treated with antibiotic despite negative throat cultures. The exact prevalence of this syndrome is not known but PFAPA seems to be far more frequent than other auto-inflammatory diseases . Since PFAPA has an unknown etiology and lacks a specific laboratory marker, the diagnosis is made by using clinical criteria which include more than three documented episodes of fever, lasting no more than five days and occurring at regular intervals at a range of three to six weeks, pharyngitis plus tender cervical lymphadenopathy or aphthous ulcers, normal growth parameters and good health between episodes . Single dose of glucocorticoids usually leads to prompt resolution of the disease. Their usefulness as therapy, however, is limited by the fact that glucocorticoid treatment results in shortening the interval between attacks in about 30 percent of case up to even weekly attacks. Prophylaxis therapy with cimetidine or colchicine has limited value and most children do
Sponsor: Rabin Medical Center

Current Primary Outcome: Change in average number of flares - documented by the use of diary [ Time Frame: baseline (canakinumab administration) and 2 months after baseline ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Time to flare - documented by the use of diary [ Time Frame: baseline (canakinumab administration) and up to 24 weeks after baseline ]
  Time to flare - period between administration of a single dose of canakinumab until the first documented PFAPA flare as reported by the patient (use of diary) and documented by the patient primary care physician and/ or the researcher in a monthly follow up visits. Will be compared to the average time between 2 consecutive flares before therapy (e.g: first documented flare- will be day 1. In the following 90 days 5 more flares (3 before screening and 2 after) = 90/5= 18d mean time to flare).
• Change in quality of life - documented by the use of questionnaire [ Time Frame: at the time of screening visit and 2 months after baseline (canakinumab administration) ]
  Parent/patient quality of life assessment measured by 100mm visual analog scale (VAS) difference at screening vs. 2 months after administration of a single dose of canakinumab.

Original Secondary Outcome:

• Time to flare - documented by the use of diary [ Time Frame: baseline (canakinumab administration) and up to 24 weeks after baseline ]
  Time to flare - period between administration of a single dose of canakinumab until the first documented PFAPA flare as reported by the patient (use of diary) and documented by the patient primary care physician and/ or the researcher in a monthly follow up visits. Will be compared to the average time between 2 consecutive flares before therapy (e.g: first documented flare- will be day 1. In the following 90 days 5 more flares (3 before screening and 2 after) = 90/5= 18d mean time to flare).
• Change in quality of life - documented by the use of questionnaire [ Time Frame: at the time of screeining visit and 2 months after baseline (canakinumab administration) ]
  Parent/patient quality of life assessment measured by 100mm visual analog scale (VAS) difference at screeining vs. 2 months after administration of a single dose of canakinumab.

Dates:
Date Received: April 27, 2016
Date Started: June 2016
Date Completion: March 2017
Last Updated: May 19, 2016
Last Verified: April 2016