Background: ALT-P1 (CJ-40002) is a long-acting recombinant growth hormone (GH) fused with NexP, which is a long-acting carrier developed by Alteogen Inc. NexP is a protein engineered recombinant alpha1 antitrypsin with further increased in vivo half-life without a native proteinase inhibitor activity. In non-clinical studies of cynomologus monkeys, the extended half-life of hGH-NexP has been successfully proved without side effects in high dose as 20 mg per kg dose.
Objective and hypotheses: Currently available GH is developed as daily injections which cause inconvenience and poor compliance for patients. ALT-P1 was developed for once-weekly administration in GH deficient adults and children. i) Safety and tolerability, ii) pharmacokinetics and pharmacodynamics of once-weekly s.c. administration of ALT-P1 was evaluated in a phase 1 study of korean healthy male volunteers.
Method: This phase 1, single-blinded, placebo-controlled, single-dosed, dose-escalated, randomized study was conducted in Yonsei University of Korea. A total of 40 subjects were enrolled and randomized to one of the five dose cohorts: 0.03, 0.06, 0.12, 0.24, and 0.35 mg/kg. In each dose cohort, six subjects were randomized into the test cohort and 2 to the placebo group. The mean age was 25.7±5.1 and the BMI was 22.0±1.7 kg/m2.
Results: No safety concerns were shown, including absence of lipoatrophy and anti-drug antibodies. Also there were no drug related severe adverse events. These results demonstrated that ALT-P1 is both non-immunogenic and highly tolerated in healthy, male subjects. Power modelling was adjusted to PK data analysis of AUC and Cmax. The terminal half-life were 19.09±6.66 h (0.12 mg/kg), 26.81±3.31 h (0.24 mg/kg), and 39.50±20.34 h (0.35 mg/kg), respectively. Furthermore, maximal IGF-1 SDS change from baseline of each dose were 1.74 (0.12 mg/kg), 2.05 (0.24 mg/kg) and 3.05 (0.35 mg/kg), respectively.
Conclusion: In conclusion, s.c. administration of single dose ALT-P1 to healthy male volunteers, demonstrated not only excellent safety and tolerability profile but also increased efficacy which can be injected once per week.