Safety and efficacy of fulranumab in osteoarthritis of the hip and knee: results from four early terminated phase III randomized studies

Abstract

Objective: To evaluate the safety and efficacy of fulranumab as adjunct or monotherapy in patients with knee or hip pain related to moderate-to-severe osteoarthritis.

Methods: Osteoarthritic patients (aged ≥18 years) from four phase 3 randomized, double-blind (DB), placebo-controlled studies were randomized to receive placebo, fulranumab 1 mg every 4 weeks (Q4wk), or 3 mg Q4wk in 16-week DB phase, followed by a 52-week post-treatment follow-up phase. Safety assessments included treatment-emergent adverse events (TEAEs), and neurological, sympathetic, and joint-related events of interest. Efficacy assessments included pain and physical function sub-scales of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores.

Results: Of 245 patients from the ITT set (median age = 64 years; 62% women), 84 (34%) completed the DB phase; the majority of discontinuations (57%) were due to early study termination. In the DB phase, the incidence of TEAEs in fulranumab 3 mg (57.8%) and 1 mg (56.8%) was similar to placebo (56.8%). Two events adjudicated as joint-related events of interest include rapidly progressive osteoarthritis and fracture of unknown etiology. There were no new neurological TEAEs. Fulranumab showed evidence of efficacy in improving pain and physical function based on WOMAC sub-scale scores. Due to premature study termination, the number of patients enrolled were too small to make any definitive efficacy claims.

Conclusions: Treatment with fulranumab was generally tolerated with no new safety signals. Within the limited sample analyzed, fulranumab showed evidence of improvement of pain and function in patients with moderate-to-severe osteoarthritis who had failed prior therapy and were candidates for joint replacement surgery.

Clinical trial registration numbers: NCT02336685; NCT02336698; NCT02289716; NCT02301234

KEY POINTS

• Fulranumab as adjuvant or monotherapy was well tolerated with no new safety signals

• Fulranumab demonstrated evidence suggestive of efficacy in osteoarthritic pain of hip and knee

• Fulranumab demonstrated evidence suggestive of improvement of pain and physical function in osteoarthritis

Keywords:

• Efficacy
• fulranumab
• osteoarthritis of the hip and knee
• safety
• WOMAC scores

Transparency

Declaration of funding

This work was supported by Janssen Research & Development, LLC, USA.

Declaration of financial/other relationships

Conception and design: K.K., S.W., P.S., J.T., J.H.; Collection and assembly of data: K.K., S.W., P.S., N.Z., J.T.; Data analysis and interpretation: K.K., S.W., P.S., N.Z., J.L., J.H., J.T. All authors are employees of Janssen Research & Development and are shareholders in the parent company (Johnson & Johnson). At the time of publication, K.K. had retired from services of Janssen Research & Development. The studies presented in this report were sponsored by Janssen Research & Development, LLC, USA. Janssen Research & Development facilitated the study design, provided writing assistance and editorial support for the manuscript, and reviewed and approved the manuscript prior to submission.

Acknowledgements

Lakshmi Kasthurirangan, PhD, SIRO Clinpharm Pvt. Ltd. provided medical writing assistance and Harry Ma, PhD, Janssen Research & Development, LLC provided additional editorial support for this manuscript. The authors thank the study participants without whom this study would not have been accomplished and also thank the investigators for their participation in this study.

Data availability

The data sharing policy of Janssen Pharmaceutical Companies of Johnson & Johnson is available at https://www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through the Yale Open Data Access (YODA) Project site at http://yoda.yale.edu.