BACKGROUND: Improving granulocyte function may represent an effective therapy for Crohn's disease (CD). We performed a Phase I-2 trial of sargramostim (SRG) in children with CD. METHODS: This was multicenter, open-label study in 6-16-year-old patients with moderate to severely active CD. Patients received either 4 or 6 microg/kg SRG subcutaneously daily for 8 weeks, with and without concomitant corticosteroids (CS). The primary endpoint was identification of a safe and tolerable dose in children. The secondary endpoint was establishment of the pharmacokinetics (PK). Efficacy, a tertiary endpoint, was measured by the Pediatric CD Activity Index (PCDAI). Response was defined as a decrease from baseline of > or =12.5 points and remission as absolute PCDAI of < or =10. RESULTS: In all, 22 patients were enrolled: 12 and 10 received 4 and 6 mg/kg, respectively; 19 completed the course. Both doses were found to be safe and well tolerated. Mild injection-site reactions occurred in 90% of patients. Three patients required dose reductions due to elevated absolute neutrophil counts. Following 4 microg/kg the mean area under the curve (AUC) was 2.64 and 2.80 ngh/mL for the 6-11- and 12-16-year-old groups, respectively. The mean half-life (t(1/2)) was 1.22 and 1.59 hours, respectively. Following 6 microg/kg, the mean AUC was 5.01 ngh/mL for the 12-16-year-old group, a 1.8-fold increase. A total of 16/18 patients (88%) achieved remission or response. CONCLUSIONS: Sargramostim at both 4 and 6 mg/kg was well tolerated. PK analysis suggested dose proportionality unaffected by CS exposure. Remission and response data are encouraging, but further trials are needed to assess efficacy.
BACKGROUND: Improving granulocyte function may represent an effective therapy for Crohn's disease (CD). We performed a Phase I-2 trial of sargramostim (SRG) in children with CD. METHODS: This was multicenter, open-label study in 6-16-year-old patients with moderate to severely active CD. Patients received either 4 or 6 microg/kg SRG subcutaneously daily for 8 weeks, with and without concomitant corticosteroids (CS). The primary endpoint was identification of a safe and tolerable dose in children. The secondary endpoint was establishment of the pharmacokinetics (PK). Efficacy, a tertiary endpoint, was measured by the Pediatric CD Activity Index (PCDAI). Response was defined as a decrease from baseline of > or =12.5 points and remission as absolute PCDAI of < or =10. RESULTS: In all, 22 patients were enrolled: 12 and 10 received 4 and 6 mg/kg, respectively; 19 completed the course. Both doses were found to be safe and well tolerated. Mild injection-site reactions occurred in 90% of patients. Three patients required dose reductions due to elevated absolute neutrophil counts. Following 4 microg/kg the mean area under the curve (AUC) was 2.64 and 2.80 ngh/mL for the 6-11- and 12-16-year-old groups, respectively. The mean half-life (t(1/2)) was 1.22 and 1.59 hours, respectively. Following 6 microg/kg, the mean AUC was 5.01 ngh/mL for the 12-16-year-old group, a 1.8-fold increase. A total of 16/18 patients (88%) achieved remission or response. CONCLUSIONS: Sargramostim at both 4 and 6 mg/kg was well tolerated. PK analysis suggested dose proportionality unaffected by CS exposure. Remission and response data are encouraging, but further trials are needed to assess efficacy.
Authors: Jonathan I Goldstein; Douglas J Kominsky; Nicole Jacobson; Brittelle Bowers; Kirsten Regalia; Gregory L Austin; Melinda Yousefi; Michael T Falta; Andrew P Fontenot; Mark E Gerich; Lucy Golden-Mason; Sean P Colgan Journal: Gastroenterology Date: 2011-04-07 Impact factor: 22.682
Authors: Grace Gathungu; Mi-Ok Kim; John P Ferguson; Yashoda Sharma; Wei Zhang; Sok Meng E Ng; Erin Bonkowski; Kaida Ning; Lisa A Simms; Anthony R Croft; Joanne M Stempak; Nicole Walker; Ning Huang; Yang Xiao; Mark S Silverberg; Bruce Trapnell; Judy H Cho; Graham L Radford-Smith; Lee A Denson Journal: Inflamm Bowel Dis Date: 2013-07 Impact factor: 5.325
Authors: I Jurickova; M H Collins; C Chalk; A Seese; R Bezold; K Lake; D von Allmen; J S Frischer; R A Falcone; B C Trapnell; L A Denson Journal: Clin Exp Immunol Date: 2013-06 Impact factor: 4.330