CJC-1295 with DAC

In two randomized, double-blind, placebo-controlled ascending-dose trials in healthy adults, single subcutaneous doses of CJC-1295 produced dose-dependent increases in mean plasma GH of 2- to 10-fold sustained for 6 or more days and IGF-I increases of 1.5- to 3-fold lasting 9-11 days. The estimated terminal half-life was 5.8-8.1 days, consistent with covalent binding to serum albumin via the Drug Affinity Complex. With multiple doses, IGF-I remained elevated above baseline for up to 28 days and there was evidence of cumulative effect; no serious adverse reactions were reported. This is the principal human trial for CJC-1295 with DAC, though the sample was small and short-term.

This is the main human study of CJC-1295 with DAC. In healthy volunteers, a single shot raised growth hormone levels several-fold for about a week and raised IGF-1 (a downstream growth factor) for up to 11 days, because the drug latches onto a blood protein and clears slowly (half-life roughly 6-8 days). Repeated dosing kept IGF-1 elevated for weeks and the drug was generally well tolerated. Human evidence is limited to a few small early-phase studies like this one.

This preclinical study characterized hGRF(1-29)-albumin bioconjugates and identified CJC-1295, a tetrasubstituted hGRF(1-29) bearing a C-terminal N-epsilon-3-maleimidopropionamide lysine derivative that reacts in vivo with the free thiol at Cys34 of serum albumin. The maleimide-albumin conjugation constitutes the Drug Affinity Complex that markedly extends plasma residence, with bioactive peptide detectable in rat plasma beyond 72 hours. In rats, CJC-1295 produced roughly a 4-fold increase in GH area-under-the-curve while retaining GRF-receptor agonist activity at the anterior pituitary.

This is the original animal study that created and named CJC-1295. Scientists attached a chemical hook to a natural growth-hormone-releasing peptide so it would grab onto albumin, an abundant blood protein, keeping it active far longer than the natural hormone. In rats the modified peptide stayed detectable for more than three days and boosted growth hormone output several-fold. It explains why the DAC version lasts so long, but the work was done in rats, not people.

In GHRH-knockout mice, a model of profound GH deficiency and growth failure, once-daily subcutaneous CJC-1295 for two weeks significantly increased body weight, body and tail length, and restored IGF-I toward normal, effectively normalizing growth. The sustained GHRH-receptor stimulation from albumin-bound CJC-1295 was sufficient to overcome the endogenous GHRH deficit. Findings support the compound's ability to drive the GH/IGF-I axis in vivo through daily dosing in a genetic deficiency model.

In mice genetically unable to make their own growth-hormone-releasing hormone, a once-a-day injection of CJC-1295 restored normal growth, increasing their size, length, and IGF-1 levels toward those of healthy mice. This shows the drug can substitute for the missing natural hormone and drive growth. As with the other supporting data, this is an animal study, so it demonstrates biological mechanism rather than proven human benefit.