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Treatment of pediatric growth hormone deficiency with human growth hormone analogues

A growth hormone deficiency, human growth hormone technology, applied in the field of application of patients with D, can solve problems such as joint pain, nausea, vomiting and injection reactions

Inactive Publication Date: 2015-12-30
AMUNIX OPERATING INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although generally well tolerated, daily rhGH therapy may cause mild to moderate headache, arthralgia, nausea, vomiting, and injection reactions

Method used

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  • Treatment of pediatric growth hormone deficiency with human growth hormone analogues
  • Treatment of pediatric growth hormone deficiency with human growth hormone analogues
  • Treatment of pediatric growth hormone deficiency with human growth hormone analogues

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1A

[0296] Example 1A - Single Dose Results

[0297] Studies have been conducted on single-dose human growth hormone analogues ( figure 1 Safety, pharmacokinetics (PK) and pharmacokinetics of the human growth hormone-XTEN (hGH-XTEN) fusion protein shown as SEQ ID NO: 1 when subcutaneously (SC) administered in pediatric patients with growth hormone deficiency. Phase 1b / 2a trial of efficacy (PD). Based on the safety profile in adults with GHD (Yuen, K.C. et al., The Journal of Clinical Endocrinology and Metabolism 98, 2595-2603 (2013)) and the possibility of achieving monthly dosing, the phase 1b / 2a study in children with GHD determined (i) safety, Tolerance, PK, and IGF-I response in children with GHD to a single dose of hGH-XTEN fusion protein (Phase 1b); and (ii) 6-month height using a fusion protein dosing regimen that normalizes IGF-I Growth rate (Phase 2a).

[0298] The study was designed to enroll 72 treatment-naive prepubertal children. Key inclusion criteria were prep...

Embodiment 1B

[0316] Example 1B - Single Dose Results

[0317] Currently approved growth hormone drugs require daily injections and thus present considerable challenges to patients with GHD. In contrast, human growth hormone analogs (( figure 1 ) shown as a human growth hormone-XTEN (hGH-XTEN) fusion protein of SEQ ID NO: 1) was developed to provide up to once-monthly dosing, helping to increase the ability of patients to comply with their regimen and improve their overall treatment outcome .

[0318] Data were collected from a phase 1b / 2a study of a novel long-acting human growth hormone (hGH-XTEN fusion protein) in prepubertal children with growth hormone deficiency (GHD). The purpose of the phase 1b study was to evaluate the single-dose safety, tolerability of hGH-XTEN fusion protein in pediatric patients with GHD; and to determine the PK (hGH-XTEN fusion protein concentration) and PD (IGF-I, IGFBP- 3) Features.

[0319] The clinical trial enrolled up to 72 treatment-first prepuber...

Embodiment 2

[0332] Example 2 - Repeat Dosing Results

[0333] VRS-317 is an amino acid sequence (XTEN) ( figure 1 A novel fusion protein (M.W.119kDa) consisting of SEQ ID NO: 1). In a phase 1 study in adults and children with GHD, VRS-317 concentrations, IGF-I and IGFBP-3 responses were dose proportional, and drug concentrations and increases in IGF-I and IGFBP-3 were sustained after a single subcutaneous injection Present for 30 days. Single-dose VRS-317 administration was safe and well tolerated, with minor injection site discomfort; no new safety signals compared to those already presented with daily rhGH products.

[0334] A repeat dosing study was conducted to determine safety, tolerability, height growth velocity, IGF-I and IGFBP-3 responses after 6 months of VRS-317 treatment. The primary endpoint was mean 6-month height growth velocity. The subjects were all prepubescent and receiving rhGH treatment for the first time. GHD is diagnosed by the following: short stature (HT-SD...

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Abstract

The present invention concerns a pediatric growth hormone deficiency (PGHD) therapy for pediatric subjects. The therapy comprises administering to the pediatric patient with PGHD a human growth hormone -XTEN (hGH-XTEN) fusion protein in therapeutically effective doses every week, every two weeks, semimonthly, every three weeks, or monthly. This therapy is not inferior compared to the height velocity achieved with daily injections of hGH not linked to XTEN over the same period.

Description

Background of the invention [0001] Human growth hormone (hGH) is naturally secreted from the anterior human pituitary gland as intermittent pulses lasting minutes to hours that typically occur during sleep. The rate and extent of hGH secretion declines with age and reaches a maximum during adolescence in normally healthy well-nourished children. hGH binds to the hGH receptor, thereby initiating signaling processes involving the STAT (signal transducer and activator of transcription), MAPK (mitogen-activated protein kinase) and PI3K (phosphoinositide-3 kinase) pathways. hGH receptor signaling activates insulin-like growth factor-I (IGF-I) gene expression, resulting in secretion of IGF-I into the circulation. IGF-I forms a complex with insulin-like growth factor binding protein-3 (IGFBP-3) and acid-labile subunit (ALS). Both IGFBP-3 and ALS expression are also regulated by hGH receptor activation. [0002] In children with growth hormone deficiency (GHD) due to lack of hGH ex...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/16A61K38/27
CPCC07K2319/00C07K14/61A61K38/27A61P5/00A61P5/06A61P5/10A61K38/17
Inventor J·L·克莱兰乔治·M·布莱特埃里克·汉弗里斯
Owner AMUNIX OPERATING INC
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