Final analysis of the phase II, randomized, double-blind, placebo-controlled trial of single dose velafermin (CG53135–05) for the prevention of oral mucositis

Abstract

6537 Background: Oral mucositis (OM) is a commonly occurring side effect of high-dose chemotherapy (HDCT) in patients (pts) undergoing autologous hematopoietic stem cell transplant (AHSCT). Velafermin, recombinant human fibroblast growth factor 20, is being investigated for prevention of OM. Velafermin promotes epithelial and mesenchymal cell proliferation in vitro and in vivo. Methods: A phase II trial was conducted to evaluate safety, efficacy, and pharmacokinetics (PK) of velafermin. Inclusion criteria: pts undergoing HDCT and AHSCT with or without total body irradiation (TBI) were enrolled. Velafermin at 0.03, 0.1, or 0.2 mg/kg or placebo was administered as single dose IV at 24h after stem cell infusion. Safety and PK were assessed. Pts were scored daily for presence of OM using the WHO grading scale. The primary endpoint was the incidence of Grade 3/4 OM. Results: A total of 212 pts were randomized to either placebo (n=51) or velafermin at 0.03 (n=50), 0.1 (n=56), or 0.2 (n=55) mg/kg (intent-to-treat or ITT sample). 206 pts (97%) received study drug or placebo. Pt diagnoses included multiple myeloma (57%), non-Hodgkin’s (25%), or Hodgkin’s (11%) lymphoma and 13 pts (6%) received TBI as part of the conditioning regimen. The Grade 3/4 OM incidence rates (%) in the placebo or velafermin arms (0.03, 0.1, and 0.2 mg/kg) were 37, 18, 38, and 36, respectively. The primary analysis of dose dependent reduction of severe OM was not statistically significant (p = 0.549). However, velafermin at 0.03 mg/kg did reduce the incidence of Grade 3/4 OM when compared to placebo alone (p = 0.031). Duration of Grade 3/4 OM was reduced significantly in the 0.03 mg/kg when every pt was evaluated or in the 0.1 mg/kg dose when only pts with Grade 3/4 OM were included in the analysis (p = 0.037 and 0.014, respectively). A total of 5 related SAEs (3 in 0.1 mg/kg, 1 in 0.03 mg/kg, and 1 in placebo cohort) occurred within 4hr of study drug infusion. All symptoms were transient. Conclusion: Single dose velafermin at 0.03mg/kg is may be active in reducing CT induced severe OM in AHSCT pts. Safety profile supports continuing study to define the optimal dose for prevention of severe OM. A new Phase II study will be conducted to confirm velafermin activity at 0.03mg/kg dose. [Table: see text]