CJC-1295 Side Effects Severity Distribution by Patient Phenotype

What the healthy-volunteer trials recorded

Teichman 2006 ran two randomized, placebo-controlled, double-blind, ascending-dose trials of 28 and 49 days in healthy adults aged 21 to 61 [2]. The first gave single doses and the second two or three weekly or biweekly doses; in FDA's summary, study 1 included 35 people given CJC-1295 and 7 given placebo [1].

Per that summary, injection-site reactions occurred in about 70% of treated subjects in study 1 and in all treated subjects in study 2; headache in 63% versus 14% on placebo in study 1; flushing, warmth and transient low blood pressure in about 30% of treated subjects in study 1; and transient diarrhea. Two subjects had transient dizziness with low blood pressure. Most events were more common at 125 or 250 micrograms/kg. No serious adverse reactions were reported, and the authors called the drug relatively well tolerated, particularly at 30 or 60 micrograms/kg [1][2].

Ionescu and Frohman 2006 gave healthy men aged 20 to 40 a single 60 or 90 micrograms/kg injection. No serious adverse events occurred; dose-dependent increases in heart rate and transient injection-site redness and tenderness were reported [1]. Trough GH rose about 7.5-fold and mean GH by 46%, with IGF-I up 45% and no significant difference between the two doses [4]. Across the studies, doses were single subcutaneous injections of roughly 30 to 250 micrograms/kg, or two to three doses given weekly or every two weeks. There is no approved dose [1][2].

The trials in people with disease

FDA found no study of any form of CJC-1295 in people with a disease. One trial in HIV-associated visceral obesity listed on ClinicalTrials.gov (NCT00267527) was terminated [1].

FDA's briefing also says ConjuChem withdrew CJC-1295 DAC from clinical trials in 2006 after a participant in a phase 2 trial in HIV lipodystrophy (192 enrolled) died. FDA cites news reports that the participant had chest discomfort 2 hours after an 11th weekly dose, that an ECG showed an acute heart attack, and that the attending physician's most likely explanation was undiagnosed coronary artery disease with plaque rupture. The data were never published, so a causal link is neither shown nor excluded [1].

Serious concerns FDA lists

FDA's compounding page lists serious adverse events associated with CJC-1295 including increased heart rate and systemic vasodilatory reaction, and notes possible immunogenicity for certain routes, impurity and characterisation problems, and limited clinical data [3]. FDA further noted that raising GH and IGF-I carries the risks printed on approved growth hormone labels, such as glucose intolerance and diabetes, fluid retention and tumour growth concerns, and that the human studies were short, small and mostly single-dose, so long-term safety is unknown [1].