Phase I trial of sargramostim in pediatric Crohn's disease

Judith R. Kelsen, Joel Rosh, Mel Heyman, Harland S. Winter, George Ferry, Stanley Cohen, Petar Mamula, Robert N. Baldassano

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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-yearold patients with moderate to severely active CD. Patients received either 4 or 6 μg/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 ≥12.5 points and remission as absolute PCDAI of ≤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 μg/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 (t1/2) was 1.22 and 1.59 hours, respectively. Following 6 μg/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.

Original languageEnglish (US)
Pages (from-to)1203-1208
Number of pages6
JournalInflammatory bowel diseases
Volume16
Issue number7
DOIs
StatePublished - Jun 24 2010

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Crohn Disease
Area Under Curve
Adrenal Cortex Hormones
Pharmacokinetics
Granulocytes
Half-Life
sargramostim
Pediatric Crohn's disease
Neutrophils
Pediatrics
Injections
Therapeutics

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Gastroenterology

Cite this

Kelsen, J. R., Rosh, J., Heyman, M., Winter, H. S., Ferry, G., Cohen, S., ... Baldassano, R. N. (2010). Phase I trial of sargramostim in pediatric Crohn's disease. Inflammatory bowel diseases, 16(7), 1203-1208. https://doi.org/10.1002/ibd.21204
Kelsen, Judith R. ; Rosh, Joel ; Heyman, Mel ; Winter, Harland S. ; Ferry, George ; Cohen, Stanley ; Mamula, Petar ; Baldassano, Robert N. / Phase I trial of sargramostim in pediatric Crohn's disease. In: Inflammatory bowel diseases. 2010 ; Vol. 16, No. 7. pp. 1203-1208.
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Kelsen, JR, Rosh, J, Heyman, M, Winter, HS, Ferry, G, Cohen, S, Mamula, P & Baldassano, RN 2010, 'Phase I trial of sargramostim in pediatric Crohn's disease', Inflammatory bowel diseases, vol. 16, no. 7, pp. 1203-1208. https://doi.org/10.1002/ibd.21204

Phase I trial of sargramostim in pediatric Crohn's disease. / Kelsen, Judith R.; Rosh, Joel; Heyman, Mel; Winter, Harland S.; Ferry, George; Cohen, Stanley; Mamula, Petar; Baldassano, Robert N.

In: Inflammatory bowel diseases, Vol. 16, No. 7, 24.06.2010, p. 1203-1208.

Research output: Contribution to journalArticle

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Kelsen JR, Rosh J, Heyman M, Winter HS, Ferry G, Cohen S et al. Phase I trial of sargramostim in pediatric Crohn's disease. Inflammatory bowel diseases. 2010 Jun 24;16(7):1203-1208. https://doi.org/10.1002/ibd.21204