Date: 2016-12-20
Type of information: Results
phase: 2
Announcement: results
Company: Galapagos (Belgium)
Product: GLPG1837
Action
mechanism: CFTR potentiator. GLPG1837 is a candidate CFTR potentiator drug.
Disease: cystic fibrosis with the G551D mutation
Therapeutic area: Rare diseases - Genetic diseases
Country: Australia, UK
Trial
details: The SAPHIRA Phase 2 program will explore the safety, tolerability and efficacy properties of GLP1837 in cystic fibrosis patients with a G551D (SAPHIRA 1) or S1251N (SAPHIRA 2) Class III mutation in six EU countries and Australia. Primary objectives are to evaluate the safety and tolerability; secondary objectives are to assess changes in sweat chloride from baseline as the biomarker of cystic fibrosis transmembrane conductance regulator (CFTR) ion channel function and to explore the changes in pulmonary function (forced expiratory volume in 1 second [FEV1]) from baseline. Both studies will include subjects treated with Kalydeco® as well as those who are naive to this drug. In each study, different doses of GLPG1837 tablets will be administered twice daily for a total duration of four weeks. The SAPHIRA 1 phase 2 study is an open-label study of three doses of GLPG1837 in at least 12 patients with the G551D mutation, is expected to begin dosing soon. (NCT02707562) The SAPHIRA 2 Phase IIa, open-label study is evaluating two doses of GLPG1837 in subjects with cystic fibrosis and the S1251N mutation. At least 6 cystic fibrosis patients with the S1251N mutation will be treated for 4 weeks, consisting of two consecutive treatment periods of two weeks evaluating one dose of GLPG1837 each. After the treatment period, there is a 7-10 days follow-up period. During the course of the study, subjects will be examined for any side effects that may occur (safety and tolerability). Changes in sweat chloride will be assessed as biomarker from baseline onwards, and changes in pulmonary function (efficacy) will be explored throughout the study. The amount of GLPG1837 present in the blood (pharmacokinetics) will also be determined.
Latest
news: * On December 20, 2016, Galapagos reported topline results from its SAPHIRA 1 Phase 2 study in cystic fibrosis patients with potentiator GLPG1837. The SAPHIRA 1 trial included 26 patients with the G551D mutation in CFTR each receiving three sequential doses of GLPG1837. Of these, 25 patients were on stable Kalydeco® treatment at screening and agreed to a one week washout prior to the start of dosing GLPG1837. One patient was naïve to Kalydeco® . All subjects received GLPG1837 125 mg bid (twice-daily) for 7 days, immediately followed by 250 mg bid for 7 days and subsequently by 500 mg bid for 14 days. A statistically significant dose dependent decrease in sweat chloride concentration was observed. At the 500 mg bid dose, sweat chloride decreased from a mean value of 98 mmol/L at baseline to 66 mmol/L (p <0.0001). For those patients exceeding the predicted target concentration, sweat chloride changed from a mean value of 94 mmol/L at baseline to 52 mmol/L. 25 patients were on stable treatment with Kalydeco® prior to this study. For these patients, mean percent predicted FEV1 (ppFEV1) levels were 74% at screening (prior to Kalydeco® washout). The one week wash-out resulted in a 5.4% mean decrease in absolute ppFEV1. At the end of treatment with GLPG1837, the ppFEV1 levels returned to the Kalydeco pre-washout levels. Overall GLPG1837 was well tolerated, with observed treatment emergent adverse events being predominantly mild or moderate, and typical for a CF patient population. One patient dropped out of the study due to an increase in non-cardiac creatine phosphokinase. * On March 16, 2016, Galapagos announced the first dosing in cystic fibrosis patients with the G551D mutation in the SAPHIRA 1 study. The full SAPHIRA Phase 2 program will explore the safety, tolerability and efficacy of GLP1837 in CF patients with a G551D (SAPHIRA 1) or S1251N (SAPHIRA 2) Class III mutation. First dosing of the exploratory study SAPHIRA 1 took place this week in Australia. First dosing in patients with the S1251N mutation in the SAPHIRA 2 study has started last month. Topline results from both SAPHIRA 1 and 2 Phase 2 studies are expected in H2 2016.
