Unintentional weight loss, or wasting, occurs in up to 30% of HIV patients and correlates with increased mortality, increased disease severity, decreased functional performance and decreased patient quality of life. Clinical trials demonstrated that recombinant human Growth Hormone (GH) is effective at stimulating weight gain and preventing further weight loss in patients with HIV-associated wasting. In particular, GH therapy increases lean tissue mass, which most closely correlates with mortality and morbidity in this patient population. GH has a short circulating half-life and must be injected every day for optimum effectiveness in this indication. Bolder BioTechnology has created novel, highly potent, long-acting GH analogs having increased circulating half-lives and superior efficacy in animal models of Growth Hormone deficiency. Based upon animal studies we anticipate that our long-acting GH analogs will be effective when administered once every 1-2 weeks in humans. The improved in vivo characteristics of these novel GH proteins will reduce the need for frequent injections, improve patient quality of life and potentially lead to improved therapeutic efficacy. The goal of this proposal is to develop one of these long-acting GH analogs for the treatment of HIV-associated wasting. During Phase I of this proposal, we will optimize the manufacturing process and produce material under GLP (Good Laboratory Practices) conditions for use in animal pharmacology and toxicology studies. During Phase I we also will design clinical protocols for Phase I safety and Phase II dose ranging effcacy studies in humans. The Phase II SBIR proposal will include production of GMP (Good Manufacturing Practices) material for clinical trials, preparation and filing of an Investigational New Drug application, and performance of the Phase I and Phase II clinical trials.
