Study design (if review, criteria of inclusion for studies)
Two placebo-controlled, phase 2a studies
Subjects homozygous for F508del (FLAMINGO) or heterozygous for F508del and a gating mutation, receiving ivacaftor (ALBATROSS).
GLPG2222, given orally once daily for 29â¯days
The primary objective of both studies was to assess safety and tolerability. Secondary objectives included assessment of pharmacokinetics, and of the effect of GLPG2222 on sweat chloride concentrations, pulmonary function and respiratory symptoms.
Fifty-nine and 37 subjects were enrolled into FLAMINGO and ALBATROSS, respectively. Treatment-related treatment-emergent adverse events (TEAEs) were reported by 29.2% (14/48) of subjects in FLAMINGO and 40.0% (12/30) in ALBATROSS; most were mild to moderate in severity and comprised primarily respiratory, gastrointestinal, and infection events. There were no deaths or discontinuations due to TEAEs. Dose-dependent decreases in sweat chloride concentrations were seen in GLPG2222-treated subjects (maximum decrease in FLAMINGO: -17.6â¯mmol/L [GLPG2222 200â¯mg], pâ¯<â¯0.0001; ALBATROSS: -7.4â¯mmol/L [GLPG2222 300â¯mg], pâ¯<â¯0.05). No significant effects on pulmonary function or respiratory symptoms were reported. Plasma GLPG2222 concentrations in CF subjects were consistent with previous studies in healthy volunteers and CF subjects.
GLPG2222 was well tolerated. Sweat chloride reductions support on-target enhancement of CFTR activity in subjects with F508del mutation(s). Significant improvements in clinical endpoints were not demonstrated. Observed safety results support further evaluation of GLPG2222, including in combination with other CFTR modulators. FUNDING: Galapagos NV. Clinical trial registration numbers FLAMINGO, NCT03119649; ALBATROSS, NCT03045523.