Efficacy and Safety of a Subcutaneous Tanezumab Titration Dosing Regimen in Subjects With Moderate to Severe Osteoarthritis of the Hip or Knee
A PHASE 3 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY OF THE ANALGESIC EFFICACY AND SAFETY OF A DOSE TITRATION REGIMEN FOR THE SUBCUTANEOUS ADMINISTRATION OF TANEZUMAB IN SUBJECTS WITH OSTEOARTHRITIS OF THE HIP OR KNEE
3 other identifiers
interventional
698
3 countries
87
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jan 2016
87 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
January 21, 2016
CompletedFirst Submitted
Initial submission to the registry
February 11, 2016
CompletedFirst Posted
Study publicly available on registry
March 3, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 5, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
May 14, 2018
CompletedResults Posted
Study results publicly available
April 23, 2019
CompletedMay 3, 2021
April 1, 2021
1.9 years
February 11, 2016
December 5, 2018
April 30, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Week 16
WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis. The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis of index joint (knee or hip) during past 48 hours. It was calculated as the mean of scores from 5 individual questions scored on a numerical rating scale (NRS) of 0 (no pain) to 10 (extreme pain), where higher scores indicated higher pain.
Baseline, Week 16
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Week 16
WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis. Physical function refers to participant's ability to move around and perform usual activities of daily living. The WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in index joint (knee or hip) during past 48 hours. It was calculated as mean of the scores from 17 individual questions scored on a NRS of 0 (minimum difficulty) to 10 (extreme difficulty), where higher scores indicated extreme difficulty/worse physical function.
Baseline, Week 16
Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis at Week 16
PGA of osteoarthritis was assessed by asking a question from participants: "Considering all the ways your osteoarthritis in your knee or hip (index joint) affects you, how are you doing today?" Participants responded on a scale ranging from 1-5, where 1=very good (no symptom and no limitation of normal activities), 2= good (mild symptoms and no limitation of normal activities), 3= fair (moderate symptoms and limitation of some normal activities), 4= poor (severe symptoms and inability to carry out most normal activities), and 5 = very poor (very severe symptoms and inability to carry out all normal activities). Higher scores indicated worsening of condition.
Baseline, Week 16
Secondary Outcomes (55)
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 2, 4, 8 and 12
Baseline, Weeks 2, 4, 8 and 12
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Week 24
Baseline, Week 24
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 2, 4, 8 and 12
Baseline, Weeks 2, 4, 8 and 12
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Week 24
Baseline, Week 24
Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis at Weeks 2, 4, 8 and 12
Baseline, Weeks 2, 4, 8 and 12
- +50 more secondary outcomes
Study Arms (3)
Placebo
PLACEBO COMPARATORplacebo administered subcutaneously at day 0 and week 8
Tanezumab 2.5 mg
EXPERIMENTALtanezumab 2.5 mg administered subcutaneously at day 0 and week 8
Tanezumab 2.5mg/5mg
EXPERIMENTALtanezumab 2.5 mg administered subcutaneously at day 0 and tanezumab 5 mg administered subcutaneously at week 8
Interventions
Patient receives one dose of placebo to match tanezumab subcutaneously on Day 1 and one dose of placebo to match tanezumab subcutaneously at Week 8.
Patient receives one dose of tanezumab 2.5 mg subcutaneously on Day 1 and one dose of tanezumab 2.5 mg subcutaneously at Week 8.
Patient receives one dose of tanezumab 2.5 mg subcutaneously on Day 1 and one dose of tanezumab 5 mg subcutaneously at Week 8.
Eligibility Criteria
You may qualify if:
- Diagnosis of Osteoarthritis of the knee or hip confirmed by X-ray
- Documented history that subject tried the following medications and had insufficient pain relief or is cannot take or tolerate them: acetaminophen, NSAIDs and either tramadol or opioids
- Meet the protocol requirements for pain at screening and pain, physical function and patient global assessment of osteoarthritis at baseline
- Willing to discontinue all pain medications except study medication and rescue medication during the course of the study and use those as directed per protocol
- Women able to have children must agree to use 2 forms of contraception during the study
You may not qualify if:
- Body Mass Index (BMI) greater than 39
- History of diseases other than osteoarthritis in a shoulder, hip or knee (example, rheumatoid arthritis, gout, joint infections, osteonecrosis)
- Patients with x-ray showing joint conditions such as osteonecrosis (dead bone) or certain types of fractures
- Patients who have had significant trauma or surgery to a knee, hip or shoulder within the previous year
- Planned surgical procedure during the study
- Patients who are largely or wholly incapacitated (example bedridden or confined to a wheelchair, permitting little or no self-care)
- Patients who would be unwilling or unable to undergo joint replacement surgery if one eventually became necessary
- Patients with significant conditions other than osteoarthritis that could interfere with assessment of pain in the joints (example fibromyalgia, lupus erythematosus)
- Patients with significant heart, neurological or psychiatric diseases
- Patients who had cancer other than certain skin cancers within the past 5 years
- Patients with alcohol, analgesic (pain medications) or drug abuse within the past 2 years
- Women who are pregnant, breast-feeding or intending to become pregnant or breast-feed during the course of the study.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Pfizerlead
Study Sites (87)
Alabama Orthopaedic Surgeons
Birmingham, Alabama, 35235, United States
Cahaba Research, Inc.
Birmingham, Alabama, 35242, United States
Arizona Research Center
Phoenix, Arizona, 85023, United States
Clinical Research Institute of Arizona, LLC
Surprise, Arizona, 85374, United States
Tucson Orthopaedic Institute
Tucson, Arizona, 85714, United States
University of Arizona Clinical and Translational Science Research Center
Tucson, Arizona, 85724, United States
Baptist Health Center for Clinical Research
Little Rock, Arkansas, 72205, United States
Advanced Research Center, Inc
Anaheim, California, 92805, United States
Medvin Clinical Research
Covina, California, 91722, United States
St. Jude Hospital Yorba Linda DBA St. Joseph Heritage Healthcare
Fullerton, California, 92835, United States
Irvine Center for Clinical Research
Irvine, California, 92614, United States
Robert L Freed, M.D., F.A.C.R / Clinical Interventions Research Institute
Irvine, California, 92618, United States
Providence Clinical Research
North Hollywood, California, 91606, United States
Artemis Institute for Clinical Research
San Diego, California, 92103, United States
California Research Foundation
San Diego, California, 92123, United States
Inland Rheumatology Clinical Trials, Inc.
Upland, California, 91786, United States
Alpine Clinical Research Center
Boulder, Colorado, 80301, United States
New England Research Associates, LLC
Bridgeport, Connecticut, 06606, United States
Stamford Therapeutics Consortium
Stamford, Connecticut, 06905, United States
Clinical Physiology Associates
Fort Myers, Florida, 33912, United States
Eastern Research, Inc.
Hialeah, Florida, 33013, United States
South Florida Research Center, Inc.
Miami, Florida, 33135, United States
New Horizon Research Center
Miami, Florida, 33175, United States
Miami Dade Medical Research Institute, LLC
Miami, Florida, 33176, United States
Compass Research, LLC
Orlando, Florida, 32806, United States
Ormond Beach Clinical Research
Ormond Beach, Florida, 32174, United States
Phoenix Clinical Research, LLC
Tamarac, Florida, 33321, United States
Bioclinica Research
The Villages, Florida, 32162, United States
Atlanta Center for Medical Research
Atlanta, Georgia, 30331, United States
Center for Advanced Research & Education (CARE)
Gainesville, Georgia, 30501, United States
East-West Medical Research Institute
Honolulu, Hawaii, 96814, United States
Medex Healthcare Research Inc
Chicago, Illinois, 60602, United States
Chicago Clinical Research Institute, Inc.
Chicago, Illinois, 60607, United States
Northwestern University Feinberg School of Medicine
Chicago, Illinois, 60611, United States
Great Lakes Clinical Trials
Chicago, Illinois, 60640, United States
Investigators Research Group, LLC
Brownsburg, Indiana, 46112, United States
Integrated Clinical Trial Services, Inc.
West Des Moines, Iowa, 50265, United States
Professional Research Network of Kansas, LLC
Wichita, Kansas, 67205-1138, United States
George Stanley Walker, MD
New Orleans, Louisiana, 70115, United States
Tristan Medical Enterprises, PC dba Regeneris Medical
North Attleboro, Massachusetts, 02760, United States
Michigan Orthopaedic & Spine Surgeons
Rochester Hills, Michigan, 48307, United States
Arthritis and Osteoporosis Treatment and Research Center
Flowood, Mississippi, 39232, United States
Office Of Stephen H. Miller, M.D.
Las Vegas, Nevada, 89144, United States
Arthritis And Osteoporosis Associates
Freehold, New Jersey, 07728, United States
New Mexico Clinical Research & Osteoporosis Center, Inc.
Albuquerque, New Mexico, 87106, United States
Drug Trials America
Hartsdale, New York, 10530, United States
Wake Research Associates, LLC
Raleigh, North Carolina, 27612, United States
Plains Clinical Research Center, LLC
Fargo, North Dakota, 58104, United States
Prestige Clinical Research
Franklin, Ohio, 45005, United States
AC Clinical Research
Tiffin, Ohio, 44883, United States
NPC Research
Oklahoma City, Oklahoma, 73109, United States
Hillcrest Clinical Research
Oklahoma City, Oklahoma, 73119, United States
University Orthopedics Center
State College, Pennsylvania, 16801, United States
Palmetto Clinical Trial Services, LLC
Greenville, South Carolina, 29601, United States
Health Concepts
Rapid City, South Dakota, 57702, United States
Quality Medical Research
Nashville, Tennessee, 37211, United States
KRK Medical Research
Arlington, Texas, 76012, United States
Tekton Research, Inc
Austin, Texas, 78745, United States
Urgent Care MD's
Baytown, Texas, 77521, United States
Arthritis Care and Diagnostic Center
Dallas, Texas, 75231, United States
T&R Clinic, PA
Fort Worth, Texas, 76117, United States
Centex Studies, Inc.
Houston, Texas, 77058, United States
BI Research Center
Houston, Texas, 77084, United States
The Pain Relief Center
Plano, Texas, 75024, United States
Center for Arthritis and Rheumatic Diseases
Chesapeake, Virginia, 23320, United States
Spectrum Medical, Inc
Danville, Virginia, 24541, United States
National Clinical Research - Richmond, Inc
Richmond, Virginia, 23294, United States
Northwest Clinical Research Center
Bellevue, Washington, 98007, United States
Aggarwal and Associates Limited
Brampton, Ontario, L6T 0G1, Canada
Manna Research Inc. (Burlington south)
Burlington, Ontario, L7R 1A4, Canada
Dawson Road Medical Centre
Guelph, Ontario, N1H 1B1, Canada
Adachi Medicine Professional Corporation
Hamilton, Ontario, L8N 1Y2, Canada
K-W Musculoskeletal Research Inc.
Kitchener, Ontario, N2M 5N6, Canada
Western Center for Public Health and Family Medicine
London, Ontario, N6G 2M1, Canada
Malton Medical Centre
Mississauga, Ontario, L4V 1P1, Canada
Rebecca Medical Associates
Oakville, Ontario, L6K 1J6, Canada
King Street Medical Clinic
Oshawa, Ontario, L1H 1G6, Canada
Bluewater Clinical Research Group
Sarnia, Ontario, N7T 4X3, Canada
Diex Recheche Montreal, Inc.
Montreal, Quebec, H2Y 1S1, Canada
Recherche Clinique Sigma inc
Québec, Quebec, G1G 3Y8, Canada
Diex Recherche Quebec Inc.
Québec, Quebec, G1S 2L6, Canada
G.R.M.O. (Groupe de recherche en maladies osseuses) Inc.
Québec, Quebec, G1V 3M7, Canada
Centre de recherche Saint-Louis
Québec, Quebec, G1W 4R4, Canada
Alpha Recherche Clinique
Québec, Quebec, G3K 2P8, Canada
Diex Research Sherbrooke Inc.
Sherbrooke, Quebec, J1L 0H8, Canada
Puerto Rico Medical Research Inc.
Ponce, PR, 00717, Puerto Rico
Mindful Medical Research
San Juan, 00918, Puerto Rico
Related Publications (17)
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.
PMID: 38650049DERIVEDGuermazi 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.
PMID: 38343426DERIVEDRen 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.
PMID: 37982583DERIVEDCarrino 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.
PMID: 37652258DERIVEDShoji 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.
PMID: 37470295DERIVEDBrown 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.
PMID: 37460782DERIVEDColloca 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.
PMID: 36621827DERIVEDHunter 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.
PMID: 36474952DERIVEDAtkinson 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.
PMID: 36301512DERIVEDMease 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.
PMID: 35980115DERIVEDSchnitzer 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.
PMID: 35960482DERIVEDConaghan 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.
PMID: 35232805DERIVEDConaghan 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.
PMID: 35105318DERIVEDBerenbaum 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.
PMID: 34626502DERIVEDBerenbaum 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.
PMID: 33973384DERIVEDSchnitzer 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.
PMID: 32252976DERIVEDSchnitzer 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.
PMID: 31265100DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Pfizer ClinicalTrials.gov Call Center
- Organization
- Pfizer, Inc.
Study Officials
- STUDY DIRECTOR
Pfizer CT.gov Call Center
Pfizer
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 11, 2016
First Posted
March 3, 2016
Study Start
January 21, 2016
Primary Completion
December 5, 2017
Study Completion
May 14, 2018
Last Updated
May 3, 2021
Results First Posted
April 23, 2019
Record last verified: 2021-04
Data Sharing
- IPD Sharing
- Will share
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.