US-based Capstone Therapeutics and its joint venture (JV) affiliate LipimetiX Development have started dosing for the AEM-28 (Apo E mimetic peptide) Phase Ib/IIa human clinical trial in refractory hypercholesterolemic patients who are already on optimal cholesterol lowering therapy but are unable to reach target cholesterol levels.
The study is the multiple ascending dose (MAD) component of a blended Phase I/II randomised, placebo-controlled, double-blinded, single centre dose escalation trial.
The single ascending dose (SAD) component of the trial, in healthy patients with elevated cholesterol, started on 8 April, and has progressed through the first five out of six groups.
The blended trial design called for start of the MAD component after establishing safety and tolerability in the first dive groups from the SAD.
Primary objectives of the MAD are to assess the safety and etermine preliminary pharmacokinetics/ pharmacodynamics of three repeated administrations of AEM-28 using the three highest doses tested in the SAD.
Fifteen subjects are planned for treatment at a hospital-based clinical site in Perth, Australia.
LipimetiX president Dennis Goldberg said apolipoprotein E (Apo E) has long been known to play a critical role in cholesterol and triglyceride metabolism, and recently to provide unique protective effects to the artery wall.
"Scientists at the University of Alabama at Birmingham, led by Dr G M Anantharamaiah, engineered AEM-28 as a small peptide that could be delivered therapeutically," Goldberg said.
"Collaboratively, we have developed a significant body of preclinical work that establishes AEM-28 and its analogues as promising commercial candidates in reducing both cholesterol and, potentially, atherosclerotic lesions."
The company said that the efficient trial design should result in topline data from the SAD in the third quarter of 2014, and from the MAD in the fourth quarter of 2014.
The JV has a development plan to pursue regulatory approval of AEM-28 as treatment for homozygous familial hypercholesterolemia and severe refractory hypercholesterolemia.