Sangamo BioSciences starts phase 2 trial of therapy diabetic neuropathy

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.

"We are excited to expand the scope of our studies on SB-509 to a more severely affected population of DN subjects," said Edward Lanphier, Sangamo's president and CEO. "Sangamo's second Phase 2 trial in DN has been designed to test if SB-509 treatment has a neuroprotective effect or if it can actually regenerate or repair damaged nerves. Currently, patients with DN are treated with analgesics and antidepressants to control pain symptoms. In contrast, SB-509 is designed to address the actual nerve damage and therefore could have a profound impact on the lives of patients suffering with diabetic neuropathy. We also have a double-blind, placebo controlled, repeat-dosing Phase 2 study in the less severe form of DN (mild to moderate) that is ongoing in multiple centers. We plan to complete accrual on both of these trials by the end of 2007 and to have data from both studies in the second half of 2008."

About the Phase 2 study of SB-509 for moderate to severe DN

The clinical trial is a single-blind, placebo-controlled, repeat-dosing study designed to evaluate the clinical safety and clinical effects of repeat administration of SB-509 in diabetics with moderate to severe diabetic peripheral sensory motor neuropathy in the legs. The trial will be conducted at multiple sites. SB-509 is an injectable formulation of plasmid DNA that encodes a ZFP TF, designed to upregulate the VEGF-A gene.

Approximately 45 subjects will be enrolled in the trial. Subjects will be randomized to one of two groups in a 2:1 ratio. The larger group (approximately 30 subjects) will be treated by intramuscular injection of 60 mg of SB-509 (30 mg of SB-509 per leg) into the lower limb every 3 months. The remaining group (approximately 15 subjects) will receive an equal volume of placebo on the same schedule. Each subject will receive a total of two treatments (Day 0 and 90). Subjects will receive injections in a distribution pattern that targets the major peripheral nerves in the legs and feet.

The symptoms of diabetic peripheral neuropathy and any changes that occur during the trial will be evaluated based on neurological examination data, electrophysiological testing data, subject neurological questionnaire, and subject pain assessment. Specifically, investigators will use the following tests: the visual analog scale for pain intensity (VASPI), total neuropathy score (TNS) to assess signs and symptoms of the condition. The TNS is a composite scoring system and is a comprehensive approach to evaluating changes in nerve health. In addition to qualitative assessment of symptoms, the TNS includes electrophysiological testing and quantitative sensory testing (QST) with the Vibratron II instrument, to assess the threshold of detection of vibration.

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