CTNI-79. PHASE 2 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF THE ANTI-NERVE GROWTH FACTOR (NGF) ANTIBODY TANEZUMAB IN SUBJECTS WITH MODERATE TO SEVERE PAIN DUE TO SCHWANNOMATOSIS

Abstract

Abstract INTRODUCTION Schwannomatosis (SWN) is a rare neurogenetic condition (prevalence 1:125,000) characterized by multiple schwannomas and severe chronic pain. Increased expression of nerve growth factor (NGF) has been identified in painful schwannomas. METHODS We conducted a single-institution, phase 2, randomized, double-blind, placebo-controlled trial of tanezumab, an anti-NGF antibody. Eligibility criteria included age ≥ 18; moderate-to-severe SWN-related pain; ability to discontinue NSAIDs; and absence of osteoarthritis. Participants were treated with tanezumab 10 mg SQ or placebo (double-blind treatment) followed by tanezumab 10 mg SQ (single-arm treatment). The primary endpoint was change in NRS-11 scores between days 1 and 57 (double-blind). Secondary endpoints included change in PROMIS-Pain Interference (PI) T-scores. RESULTS Nine subjects were enrolled (median age 44 years, 7 females). At baseline, mean NRS-11 score was 7.6 (SD 2.1) and mean PROMIS-PI T-score was 63.2 (SD 6.6). During double-blind treatment, four participants were randomized to receive tanezumab (early group) and five were randomized to placebo (delayed group). For the early group, the mean change in NRS-11 score was -2.5 (SD 4.5) after initial tanezumab and 0 (SD 0) with continued treatment. For the delayed group, the mean change in NRS-11 score was -0.4 (SD 2.1) with placebo and -1.4 (SD 1.9) after tanezumab. For the early group, the mean change in PROMIS-PI T-score was -6.2 (SD 10.9) after initial tanezumab and -0.4 (SD 2.0) with continued treatment. For the delayed group, the mean change in PROMIS-PI T-score was 1.1 (SD 2.9) after placebo and -3.3 (SD 4.1) after tanezumab. Discussion: For SWN patients with moderate-to-severe pain, addition of tanezumab was associated with decreases in pain intensity and pain interference. Although these changes reflect clinically meaningful differences per published literature, they were not statistically significant. This study was underpowered due to poor accrual and a larger study in this patient population is warranted.