drugset / Trial / NCT02697773
Efficacy and Safety of a Subcutaneous Tanezumab Titration Dosing Regimen in Subjects With Moderate to Severe Osteoarthritis of the Hip or Knee
RandomizedParallel-groupQuadruple-blindTreatment
Summary
The primary purpose of this study is to evaluate the efficacy of a titration arm of tanezumab in which treatment is started at a lower dose (2.5 mg) and increased to a higher dose (5 mg) at Week 8, compared to giving 2 doses of tanezumab 2.5 mg or 2 doses of placebo. The study also evaluates the safety of the treatment regimens.
Timeline
- Start
- 2016-01-21
- Primary completion
- 2017-12-05
- Completion
- 2018-05-14
Outcome
Met primary endpoint
paper tanezumab, compared with placebo, resulted in statistically significant improvements in scores assessing pain and physical function, and in PGA-OA PMID 31265100 ↗
registry analysis (superiority test); Placebo vs Tanezumab 2.5 mg; p = 0.0129; Least Square Mean Difference -0.60 (95% CI -1.07 to -0.13) NCT02697773 ↗
registry analysis (superiority test); Placebo vs Tanezumab 2.5 mg; p = 0.0065; Least Square Mean Difference -0.66 (95% CI -1.14 to -0.19) NCT02697773 ↗
registry analysis (superiority test); Placebo vs Tanezumab 2.5 mg; p = 0.0109; Least Square Mean Difference -0.22 (95% CI -0.39 to -0.05) NCT02697773 ↗
Publications
- Schnitzer TJ, Conaghan PG, Berenbaum F, Abraham L, Cappelleri JC, Bushmakin AG, Viktrup L, Yang R, Brown MT. Effect size varies based on calculation method and may affect interpretation of treatment effect: an illustration using randomised clinical trials in osteoarthritis. Adv Rheumatol. 2024 Apr 22;64(1):31. doi: 10.1186/s42358-024-00358-y.
- Guermazi A, Roemer FW, Kompel AJ, Diaz LE, Crema MD, Brown MT, Hickman A, Pixton GC, Viktrup L, Fountaine RJ, Burr A, Sherlock SP, West CR. Inter-Reader Consistency and Exclusionary Findings During Radiographic Screening for Phase 3 Trials of Tanezumab in Patients With Osteoarthritis. Osteoarthr Imaging. 2022 Sep-Dec;2(3-4):100082. doi: 10.1016/j.ostima.2022.100082. Epub 2022 Nov 15.
- Ren J, Bushmakin AG, Cislo PR, Abraham L, Cappelleri JC, Dworkin RH, Farrar JT. Meaningful within-patient change for clinical outcome assessments: model-based approach versus cumulative distribution functions. J Biopharm Stat. 2025 Aug;35(5):826-838. doi: 10.1080/10543406.2023.2281575. Epub 2023 Nov 20.
- Carrino JA, McAlindon TE, Schnitzer TJ, Guermazi A, Hochberg MC, Conaghan PG, Brown MT, Burr A, Fountaine RJ, Pixton GC, Viktrup L, Verburg KM, West CR. Characterization of adverse joint outcomes in patients with osteoarthritis treated with subcutaneous tanezumab. Osteoarthritis Cartilage. 2023 Dec;31(12):1612-1626. doi: 10.1016/j.joca.2023.08.010. Epub 2023 Aug 29.
- Shoji S, Suzuki A, Nouri P, Cai CH, Gaitonde P, Marshall S. Prediction of relative change in free nerve growth factor following subcutaneous administration of tanezumab, a novel monoclonal antibody to nerve growth factor. CPT Pharmacometrics Syst Pharmacol. 2023 Sep;12(9):1358-1370. doi: 10.1002/psp4.13015. Epub 2023 Jul 31.
- Brown MT, Cornblath DR, Koltzenburg M, Gorson KC, Hickman A, Pixton GC, Gaitonde P, Viktrup L, West CR. Peripheral Nerve Safety of Nerve Growth Factor Inhibition by Tanezumab: Pooled Analyses of Phase III Clinical Studies in Over 5000 Patients with Osteoarthritis. Clin Drug Investig. 2023 Jul;43(7):551-563. doi: 10.1007/s40261-023-01286-3. Epub 2023 Jul 18.
- Colloca L, Dworkin RH, Farrar JT, Tive L, Yang J, Viktrup L, Dasic G, West CR, Whalen E, Brown MT, Gilbert SA, Verburg KM. Predicting Treatment Responses in Patients With Osteoarthritis: Results From Two Phase III Tanezumab Randomized Clinical Trials. Clin Pharmacol Ther. 2023 Apr;113(4):878-886. doi: 10.1002/cpt.2842. Epub 2023 Jan 31.
- Hunter DJ, Schnitzer TJ, Hall J, Semel D, Davignon I, Cappelleri JC, Bushmakin AG, Abraham L. Time to first and sustained improvement in WOMAC domains among patients with osteoarthritis receiving tanezumab. Osteoarthr Cartil Open. 2022 Jul 2;4(3):100294. doi: 10.1016/j.ocarto.2022.100294. eCollection 2022 Sep.
- Atkinson J, Edwards RA, Bonfanti G, Barroso J, Schnitzer TJ. A Two-Step, Trajectory-Focused, Analytics Approach to Attempt Prediction of Analgesic Response in Patients with Moderate-to-Severe Osteoarthritis. Adv Ther. 2023 Jan;40(1):252-264. doi: 10.1007/s12325-022-02336-6. Epub 2022 Oct 27.
- Mease P, Kuritzky L, Wright WL, Mallick-Searle T, Fountaine R, Yang R, Sadrarhami M, Faison W, Johnston E, Viktrup L. Efficacy and safety of tanezumab, NSAIDs, and placebo in patients with moderate to severe hip or knee osteoarthritis and a history of depression, anxiety, or insomnia: post-hoc analysis of phase 3 trials. Curr Med Res Opin. 2022 Nov;38(11):1909-1922. doi: 10.1080/03007995.2022.2113689. Epub 2022 Aug 28.
- Schnitzer TJ, Bonfanti G, Atkinson J, Donevan S, Viktrup L, Barroso J, Whalen E, Edwards RA. Characterizing 16-Week Responder Profiles Using Group-Based Trajectory Modeling in Over 4300 Clinical Trial Participants Receiving Pharmaceutical Treatment for Moderate to Severe Osteoarthritis. Adv Ther. 2022 Oct;39(10):4742-4756. doi: 10.1007/s12325-022-02290-3. Epub 2022 Aug 12.
- Conaghan PG, Dworkin RH, Schnitzer TJ, Berenbaum F, Bushmakin AG, Cappelleri JC, Viktrup L, Abraham L. WOMAC Meaningful Within-patient Change: Results From 3 Studies of Tanezumab in Patients With Moderate-to-severe Osteoarthritis of the Hip or Knee. J Rheumatol. 2022 Jun;49(6):615-621. doi: 10.3899/jrheum.210543. Epub 2022 Mar 1.
- Conaghan PG, Abraham L, Viktrup L, Cislo P. Impact of tanezumab on health status, non-work activities and work productivity in adults with moderate-to-severe osteoarthritis. BMC Musculoskelet Disord. 2022 Feb 1;23(1):106. doi: 10.1186/s12891-022-05029-x.
- Berenbaum F, Schnitzer T, Kivitz A, Viktrup L, Johnston E, Yang R, Whalen E, Tive L, Semel D. Gender, age, disease severity, body mass index and diabetes may not affect response to subcutaneous tanezumab in patients with osteoarthritis after 16 weeks of treatment. A subgroup analysis of placebo-controlled trials. Int J Clin Pract. 2021 Dec;75(12):e14975. doi: 10.1111/ijcp.14975. Epub 2021 Oct 21.
- Berenbaum F, Schnitzer TJ, Kivitz AJ, Viktrup L, Hickman A, Pixton G, Brown MT, Davignon I, West CR. General Safety and Tolerability of Subcutaneous Tanezumab for Osteoarthritis: A Pooled Analysis of Three Randomized, Placebo-Controlled Trials. Arthritis Care Res (Hoboken). 2022 Jun;74(6):918-928. doi: 10.1002/acr.24637. Epub 2022 Mar 25.
- Schnitzer TJ, Khan A, Bessette L, Davignon I, Brown MT, Pixton G, Prucka WR, Tive L, Viktrup L, West CR. Onset and maintenance of efficacy of subcutaneous tanezumab in patients with moderate to severe osteoarthritis of the knee or hip: A 16-week dose-titration study. Semin Arthritis Rheum. 2020 Jun;50(3):387-393. doi: 10.1016/j.semarthrit.2020.03.004. Epub 2020 Mar 19.
- Schnitzer TJ, Easton R, Pang S, Levinson DJ, Pixton G, Viktrup L, Davignon I, Brown MT, West CR, Verburg KM. Effect of Tanezumab on Joint Pain, Physical Function, and Patient Global Assessment of Osteoarthritis Among Patients With Osteoarthritis of the Hip or Knee: A Randomized Clinical Trial. JAMA. 2019 Jul 2;322(1):37-48. doi: 10.1001/jama.2019.8044.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Tanezumab | Monoclonal antibody | 2.5 mg | Subcutaneous |
| Subject | Tanezumab | Monoclonal antibody | 5 mg | Subcutaneous |