Background: This study was designed to evaluate the efficacy and safety of fulranumab, a fully human monoclonal antibody directed against nerve growth factor (NGF), for pain relief in patients with interstitial cystitis/bladder pain syndrome (IC/BPS).
Methods: In this multicenter, double-blind study, adults with IC/BPS (i.e., interstitial cystitis symptom index [ICSI] total score ≥8) accompanied by chronic, moderate-to-severe pain were randomized to fulranumab 9 mg or matching placebo, administered subcutaneously at weeks 1, 5, and 9. The primary efficacy endpoint was change from baseline to study endpoint (week 12 or at withdrawal) in average daily pain intensity score. Key secondary endpoints included change from baseline to study endpoint in worst pain intensity score, ICSI total score, Pelvic Pain and Urgency/Frequency total score, Patient Perception of Bladder Condition score, and global response assessment.
Results: This study was terminated prematurely based on concern that this class may be associated with rapidly progressing osteoarthritis or osteonecrosis. Thirty-one patients (of the targeted 70 patients) were randomized, 17 to placebo and 14 to fulranumab, with 15 and 10 patients, respectively, receiving all 3 doses of double-blind treatment. In ANOVA analyses, there was no statistically significant difference between treatment groups for the primary endpoint (LS mean difference [95% CI] vs. placebo, -0.2 [-1.52, 1.10]) or any of the secondary endpoints. Fulranumab was well tolerated, with no patient discontinuing due to an adverse event or experiencing a joint-related serious adverse event over a 26-week follow-up period. No events related to the neurologic or motor systems were reported.
Conclusions: Efficacy was not demonstrated in the present study with the single dose tested and a limited sample size, leading to lack of statistical power. These findings do not exclude the possibility that fulranumab would provide clinical benefit in a larger study and/or specific populations (phenotypes) in this difficult to treat pain condition.
Trial registration: NCT01060254 , registered January 29, 2010.
Keywords: Analgesia; Bladder; Fulranumab; Interstitial cystitis; Pain.