Clinical Research Studies

This study will be the first prospective study of alpelisib in participants with PROS. Local overgrowth or hemihypertrophy, mostly progressive, is the most frequently observed manifestation of the disease, often causing functional and/or mobility impairment and reduction in health related quality of life. The first experience with alpelisib in overgrowth related to mutation in PIK3CA gene provides the direct evidence of clinical improvement in participants supporting PIK3CA inhibition as a promising therapeutic strategy in participants with PROS. PROS is a serious condition with no approved pharmacological treatment targeting the underlying cause of the disease. Current therapy includes debulking surgery, amputation, and/or endovascular occlusive procedures and mainly addresses symptoms and complications of the disease. There is a high unmet medical need for an effective systemic treatment. The purpose of this study is to assess the efficacy, safety/tolerability and evaluate pharmacokinetics (PK) of alpelisib in participants of different ages with confirmed diagnosis of PROS. As the disease continues throughout the participant life and may be diagnosed at different time points (Keppler-Noreuil et al 2014), the study will enroll adult participants (Group 1; treated with film-coated tablets (FCT)), 6-17 years old pediatric participants (Group 2; treated with FCT), and two exploratory sets of 2-5 years old pediatric participants (Group 3 treated with granules and Group 4 treated with FCT). Group 3 will be enrolled after the completion of the primary analysis when the efficacy, safety and PK data will be available from the participants in Groups 1 and 2 in addition to the data from Group 4 as available, in order to select the recommended dose for participants in Group 3. Recruitment of participants in Group 3 will start only after submission and approval of a Substantial Global Protocol Amendment specific to this group. Group 4 will be enrolled before Group 3 and immediately after implementation of this Global Protocol Amendment 01.