Sangamo BioSciences has announced that the company has initiated a repeat-dosing, multi-center Phase 2 clinical trial of SB-509 in subjects with moderate to severe diabetic peripheral sensory motor neuropathy (DN).
The clinical trial is a randomized, single-blind, placebo-controlled, repeat-dosing study designed to evaluate the clinical safety and clinical effects of repeat administration of SB-509 in diabetic subjects that have unmeasurable nerve conduction velocity (NCV) in at least one of the nerves in the leg. SB-509 is an injectable formulation of plasmid DNA that encodes a zinc finger DNA-binding protein transcription factor (ZFP TF(TM)), designed to upregulate the vascular endothelial growth factor A (VEGF-A) gene. Sangamo also has an ongoing Phase 2 clinical trial of SB-509 in subjects with mild to moderate DN.
"In our Phase 1 studies we noted interesting clinical improvements in a number of subjects and have initiated this Phase 2 trial to follow up on those observations," said Dale Ando, M.D., Sangamo's vice-president of therapeutic development and chief medical officer. "In addition to improvement in total neuropathy score (TNS) and quantitative sensory testing (QST), three subjects with so-called "blocked nerves" or unmeasurable nerve conduction velocity measurements in the leg showed recovered and improved NCV over a six-month follow-up period after a single treatment with SB-509. As these observations were made in the Phase 1 trial, which studied only a small number of subjects, we have initiated a larger Phase 2 trial to further investigate this finding. Our primary objective in this Phase 2 study will be to determine the effect of treatment with SB-509 on the clinical profile of neurologic damage in association with DN and particularly, in light of our Phase 1 data, the potential effects on nerve regeneration or regrowth. We will assess subject's symptoms by measuring NCV, the rate at which a nerve conducts an electrical signal, QST, which measures perception of vibration, and improvements in average total neuropathy score (TNS), a composite of several measurements including neurologic exam, QST, NCV and neurologic symptoms."
Activation of VEGF-A has been demonstrated to have potent and direct neurotrophic and neuroprotective properties. In preclinical animal efficacy studies in a diabetic rat model, SB-509 has proven effective in protecting motor and sensory nerve function from diabetes-induced nerve damage. Data from Sangamo's Phase 1 trials demonstrate that a single treatment of SB-509 was well-tolerated and that no drug-related severe adverse events were observed. Injection site reactions were the most common adverse events reported in both treated and placebo groups and were mild and reversible. Importantly, subjects in both Phase 2 studies are being treated within the pharmacologically effective dose range that had been demonstrated to be efficacious in preclinical animal studies.