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Clinical Trials

Date: 2017-02-16

Type of information: Publication of results in a medical journal

phase: 2

Announcement: publication of results in the Journal of Clinical Endocrinology and Metabolism.

Company: Ascendis Pharma (Denmark)

Product: TransCon Growth Hormone

Action mechanism:

hormone/proteine. TransCon Growth Hormone is a prodrug that releases unmodified growth hormone, thus maintaining the same mode of action as currently prescribed daily growth hormone therapies. Clinical studies of TransCon Growth Hormone have demonstrated a comparable efficacy, safety, tolerability and immunogenic profile to that of daily growth hormone.

Disease: growth hormone deficiency

Therapeutic area: Endocrine diseases - Hormonal diseases

Country:

Trial details:

The Phase 2 pediatric study is being conducted to investigate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of TransCon Growth Hormone in up to 52 treatment-naïve pre-pubertal patients with growth hormone deficiency, who meet internationally recognized criteria for growth hormone deficiency. The study is a 6-month multi-center, randomized study comparing three dose levels of TransCon Growth Hormone (0.14; 0.21; and 0.30 mg hGH/kg/week), administered once per week, to the active control Genotropin (0.21 mg hGH/kg/week), administered as 7 daily injections. The efficacy endpoint is height velocity at six months.

 

Latest news:

* On February 16, 2017, Ascendis Pharma announced the publication of its previously presented pediatric phase 2 trial of TransCon Growth Hormone in the Journal of Clinical Endocrinology and Metabolism. The authors concluded that once-weekly, sustained release TransCon Growth Hormone was comparable to daily growth hormone in terms of efficacy, safety and tolerability in children with growth hormone deficiency (GHD). Current GHD treatment requires daily growth hormone injections for many years. However, the administrative burden often results in at least one missed injection per week, contributing to suboptimal outcomes. Currently, there are no long-acting growth hormone treatment options commercially available in the United States or Europe.TransCon Growth Hormone is designed to release unmodified growth hormone that diffuses freely into the body's tissues, where it may carry out the effects of native growth hormone with easy-to-remember weekly dosing. Separately, results of a Phase 2 study evaluating the safety, pharmacokinetics, and pharmacodynamics of TransCon Growth Hormone in adult patients with GHD were published online in the journal Endocrine Connections. Based on the positive Phase 2 results in pediatric patients, Ascendis has an ongoing global Phase 3 trial of TransCon Growth Hormone compared to daily growth hormone. The randomized, active-controlled heiGHt Trial aims to enroll 150 pediatric patients with GHD by the end of 2017. 

* On July 30, 2015, Ascendis Pharma, a biotechnology company that applies its innovative TransCon technology to address significant unmet medical needs, announced positive top-line results from a six-month Phase 2 study to evaluate the safety and efficacy of once-weekly TransCon Growth Hormone in 53 treatment-naïve, pre-pubertal children with growth hormone deficiency, or GHD.The Phase 2 pediatric study was conducted to investigate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of TransCon Growth Hormone in treatment-naïve pre-pubertal children with growth hormone deficiency, or GHD, who meet internationally recognized diagnostic criteria for GHD. The study enrolled 53 patients into the treatment phase and was a 6-month multi-center, randomized, open-label study comparing three dose levels of TransCon Growth Hormone (0.14; 0.21; and 0.30 mg hGH/kg/week), administered once per week, to the active control Genotropin (0.21 mg hGH/kg/week), administered as a daily injection.

Highlights from the top-line analysis include:

• mean annualized height velocities among the three dosing levels administered weekly ranged from 11.9 cm for the 0.14 mg/kg/week dose to 13.9 cm for the 0.30 mg/kg/week dose, which were comparable to 11.6 cm for the active comparator, daily injections of Genotropin® at a 0.21 mg/kg/week dose;
• there were no reports of drug-related serious or unexpected adverse events;
• injection site reactions were generally mild and transient and were observed at a rate that was similar to the daily hGH control arm;
• there were no observations of injection site nodule formation or lipoatrophy;
• low immunogenicity consistent with published data for daily growth hormone;
• maximum hGH blood concentration was comparable between equivalent weekly doses of TransCon Growth Hormone and daily hGH; and
• a dose-proportional increase in IGF-I levels was observed following dosing of the three TransCon Growth Hormone dose levels. Consistent with expectations, transient point values of IGF-I standard deviation score > +2 have been observed in a small number of patients and primarily in the high-dose treatment arm.


Mean Annualized Height Velocity at 6 month

Mean Annualized Height Velocity at 6 months


The data announced represent a top-line analysis, and Ascendis Pharma intends to release the full data set for the Phase 2 pediatric study in early October 2015 at the annual meeting of the European Society for Paediatric Endocrinology, and maintains its plans to initiate a Phase 3 pediatric study of TransCon Growth Hormone in mid-2016. As currently planned, this pivotal study will be a 12-month, parallel-group study evaluating a single dose of TransCon Growth Hormone versus daily injections of growth hormone, and will be conducted in centers across Europe and North America.

* On September 16, 2014, Ascendis Pharma announced positive interim results from its ongoing Phase 2 pediatric study to evaluate once-weekly TransCon Growth Hormone in children with growth hormone deficiency, or GHD. The full interim results will be presented at the 7th International Congress of the GRS and IGF Society, being held October 15-18, 2014, in Singapore.
This interim analysis consists of 25 patients, which represents approximately 50% of the anticipated total enrollment in the study, completing three months of the total six months of treatment. Key conclusions from the interim analysis include:
• mean annualized height velocities ranged from 13.0 cm to 14.1 cm for the three weekly dose levels of TransCon Growth Hormone, which were comparable to the active comparator, daily injections of Genotropin®;
• there have been no reports of serious or unexpected adverse events;
• injection site reactions were generally mild and transient and occurred in only a few patients;
• thus far, there have been no observations of injection site nodule formation or lipoatrophy; and
• a dose-proportional increase in IGF-I levels was observed following dosing of the three TransCon Growth Hormone doses. Transient point values of IGF?I SDS > +2 have been observed in a small number of patients and only in the high-dose treatment arm.
The protocol for this Phase 2 pediatric study calls for two interim data analyses. This interim analysis reports height velocity in 50% of the evaluable patients completing the first three months of the study. In the first quarter of 2015, Ascendis Pharma plans to report six-month height velocity data from 50% of the patients completing the Phase 2 pediatric study, and top-line data for all patients in the study in mid-2015.

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