• The primary outcome is to establish that XSCID patients treated with IGF-1 do not experience more than the expected rate of drug-related adverse events than non-XSCID children receiving IGF-2 therapy, which is estimated at 5 percent. [ Time Frame: 1-year ] [ Designated as safety issue: Yes ]
  

• The primary objective is to evaluate the safety of treating XSCID children with growth failure using IGF-1. The secondary objective is to evaluate the efficacy of IGF-1 treatment for growth failure in children with XSCID. [ Time Frame: 1-year ] [ Designated as safety issue: No ]
  

Drug: Increlex
N/A
Procedure: Arginine Provocation Test
N/A
Procedure: Clonidine Provocation Test
N/A
Procedure: IGF-1 Generation Test
N/A
Drug: IVIG
N/A
Procedure: Haplo-Identical Bone Marrow Transplant
N/A

This is a Phase 2 protocol evaluating the safety and efficacy of standard dose insulin-like growth factor-1 (IGF-1) for the treatment of growth failure in patients diagnosed with X-linked severe combined immunodeficiency (XSCID). This condition is a fatal inherited immunodeficiency caused by defects in the common cytokine receptor gamma chain (gc), a subunit shared by many cytokine receptors. The common gamma subunit signals through the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, a complex intracellular signaling pathway used by many cytokines and growth factors, including growth hormone (GH). Studies have suggested that the gc defect may result in hyporesponsiveness to GH. This is supported by a report of GH hyporesponsiveness in an XSCID child that was successfully ameliorated following immune reconstitution using bone marrow transplantation (BMT). Haplo-identical BMTs for XSCID children often achieve only partial immune reconstitution, and many BMT recipients experience ongoing problems with growth failure, achieving heights well below 2 standard deviations for their chronological age. It is possible that in these partially corrected conditions, administration of IGF-1, a substance the body produces downstream in response to GH, may achieve an improved growth response.

This study proposes to evaluate the safety and efficacy of Increlex(Trademark) (recombinant human IGF-1) for the treatment of patients with XSCID who have growth failure (children with heights less than 3rd percentile for age). Increlex(Trademark) is a Food and Drug Administration-approved drug for treatment of growth hormone non-responsiveness in the general population of children with growth hormone hyporesponsiveness or primary IGF-1 deficiencies. The scientific objectives are to determine safety and to assess the efficacy of using subcutaneous IGF-1 in XSCID patients with growth failure. The long-term goal of this study is to establish improved treatment regimens for growth failure in children with XSCID.