Abstract Details

Title Peripheral Nerve Safety Measures in a Multicenter, Double-Blind, Randomized, Placebo Controlled, Dose-Ranging Study of Fulranumab in Patients with Painful Diabetic Neuropathy

Topic Clinical Neurophysiology

Presentation(s) P01 - (-)

Poster/Presentation
Number 035

Objective

Background Chronic anti-NGF activity may adversely affect nerve function. To assess progressive neuropathy risk, IENFD, peripheral nerve electrophysiology (nerve conduction velocity [NCV]) and a quantitative neurologic exam (i.e., Total Neuropathy Score-nurse, TNSn) were evaluated in a double-blind (DB), placebo-controlled, phase-2 trial of fulranumab's efficacy and safety, in patients with moderate to severe diabetic neuropathic pain.

Design/Methods Eligible patients were randomized (3:2:2:3) to placebo or fulranumab (1-, 3-, or 10-mg; every 4 weeks [Q4wk] subcutaneously).

Results At the request of the FDA, this study, and others exploring anti-NGF therapy, were terminated early. The efficacy and general tolerability of fulranumab at the time of termination has been previously reported. The change from baseline (95% CI) was evaluated for IENFD and NCV at screening, and study weeks 13 and 53, for TNSn every 4 weeks (N=59). There were no significant decrements in IENFD or NCV and associated response amplitudes in any of the four nerves evaluated (i.e., ulnar and median sensory nerve; ulnar and peroneal motor nerve). There were also no significant deficits in the TNSn composite measures or in its subcomponents (i.e., sensory, motor and autonomic symptoms; distal-to-proximal changes in pin and vibration sensibility). Finally, the analgesia observed in several patients, as determined by change in pain scores, was not associated with decrements in either IENFD or electrophysiology.

Conclusions There is no evidence that, at the doses and for the period studied, fulranumab was associated with an induced decrement in nerve function. An adequately powered and longer duration study is required to confirm these observations.

Authors/Disclosures
Michael J. Polydefkis, MD, FAAN (Johns Hopkins University School of Medicine) PRESENTER	Dr. Polydefkis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alnylam Pharmaceuticals. Dr. Polydefkis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Akcea. Dr. Polydefkis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Vertex Pharmaceutical . Dr. Polydefkis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen-Idec. Dr. Polydefkis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pfizer.
	No disclosure on file
Gary J. Romano, MD, PhD (Neurotherapeutic Development Advisors, LLC)	Dr. Romano has received personal compensation for serving as an employee of Alector. Dr. Romano has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for ALector. Dr. Romano has or had stock in Alector.
	No disclosure on file
David R. Cornblath, MD	Dr. Cornblath has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Octapharma. Dr. Cornblath has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Annexon. Dr. Cornblath has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Pfizer. Dr. Cornblath has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Grifols. Dr. Cornblath has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cigna. Dr. Cornblath has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alnylam. Dr. Cornblath has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Anavex. Dr. Cornblath has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hansa. Dr. Cornblath has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for MPTP. Dr. Cornblath has received intellectual property interests from a discovery or technology relating to health care.
John Thipphawong, MD (JANSSEN)	No disclosure on file
	No disclosure on file
	No disclosure on file
Teri Schreiner, MD, MPH, FAAN (University of Colorado/ Children's Hospital of Colorado)	The institution of Dr. Schreiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CDC. Dr. Schreiner has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. The institution of Dr. Schreiner has received research support from Roche Genentech.

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