Information Request for BLA125478/0, January 15, 2014 - Ragwitek

From:Rivers, Katie
Sent: Wednesday, January 15, 2014 11:17 AM
To: 'Greenfeder, Scott'
Cc: Valenti, Elizabeth
Subject: Information Request for BLA125478/0
Dear Scott,
We have the following IRs for your BLA, STN 125478/0, regarding your proposed pediatric plan:
1.The study to demonstrate efficacy in children must be powered to demonstrate that the point estimate of the change in TCS is at most -15%, and that the upper limit of the 95% confidence interval is at most -10%. It is unclear that the proposed study of 350 subjects, randomized equally to Ragwitek:Placebo is powered accordingly. Please comment and revise your pediatric plan as necessary to meet these requirements.
2.We recognize that an efficacy study of 175 children and adolescents who are treated with Ragwitek may provide a reliable estimate of incidence of the most common local adverse events (e.g. throat irritation, oral edema, oral pruritus). Please revise your sample size to ensure that your proposed study will detect severe or systemic reactions which occur less frequently, such as 0.2-0.3%. Subject enrollment should be stratified across the age range 5 to <18 years of age and include an adequate number of subjects to account for attrition during the study.
3.The pediatric safety studies must be for a duration of exposure similar to the treatment regimen that will be prescribed to patients, and must include treatment throughout the ragweed pollen season. Please revise your pediatric plan to meet these requirements.

Please let me know if you have any questions. 
Thank you, 
Katie
Katie H. Rivers, MS
Regulatory Project Manager, CMC1
FDA/CBER/OVRR/DVRPA
1401 Rockville Pike, HFM-481
Rockville, MD 20852
Phone 301-796-2640
Fax 301-827-3877

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