Use of a novel reversible albumin-binding human growth hormone (GH) derivative administered subcutaneously once weekly for 4 weeks was safe and effective in adults with growth hormone deficiency, according to a phase I, randomized, open-label trial.
Results from a recent clinical trial of the agent, known as NNC0195-0092 and being developed by Norvo Nordisk, indicated the feasibility of a once-weekly dosing regimen in healthy men (J Clin Endocrinol Metab. 2014;99:E1819-29). The purpose of the current study was to report the first data obtained from a multiple-dose trial of NNC0195-0092 conducted in men and women at three hospitals in Denmark and one in Sweden.
“GH is currently administered as daily subcutaneous injections; however, a long-acting GH formulation that decreases injection frequency may improve treatment adherence and reduce the inconvenience associated with daily injections,” researchers led by Dr. Michael Højby Rasmussen wrote in the article published online Jan. 4 in the Journal of Clinical Endocrinology and Metabolism (2016. doi: 10.1210/jc.2015-1991). They went on to note that the plasma half-life of therapeutic peptides such as GH can be extended through binding to serum albumin, which “has a high affinity and binding capacity for fatty acids, and acylation of fatty acids to therapeutic proteins has been used to facilitate binding of these molecules to circulating albumin. In NNC0195-0092, fatty acids with noncovalent albumin-binding properties have been attached by acylation.”
Dr. Rasmussen of Novo Nordisk, Denmark, and his associates reported results from 25 men and nine women with a mean age of 53 years who were assigned into four cohorts of eight subjects and randomized to receive once-weekly NNC0195-0092 for 4 weeks in doses that ranged from 0.02 to 0.12 mg/kg, or daily injections of Norditropin NordiFlex for 4 weeks with a dose replicating the pretrial dose of somatropin. They found that the number of adverse events was similar at the 0.02, 0.04, and 0.08 mg/kg doses of NNC0195-0092, compared with the daily injections of Norditropin NordiFlex, while the number of adverse events was greatest at the 0.12 mg/kg dose of NNC0195-0092.
“No clinically significant safety and tolerability signals causally related to NNC0195-0092 were identified, nor were any immunogenicity concerns revealed,” the investigators concluded. “The IGF-I profiles were consistent with a once-weekly treatment profile of NNC0195-0092 at a starting dose of 0.02-0.04 mg/kg/wk.”
The trial was supported by Novo Nordisk. Dr. Rasmussen disclosed that he is an employee of the company.