Clinical trial NCT02697773: Efficacy and Safety of a Subcutaneous Tanezumab Titration Dosing Regimen in Subjects With Moderate to Severe Osteoarthritis of the Hip or Knee
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Osteoarthritis, Knee
Osteoarthritis, Hip
Keywords: osteoarthritis of the knee
osteoarthritis of the hip
nerve growth factor inhibitor
tanezumab
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2016-03-03
Enrollment: 698
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Week 16
timeFrame: Baseline, Week 16
measure: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Week 16
timeFrame: Baseline, Week 16
measure: Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis at Week 16
timeFrame: Baseline, Week 16
Secondary outcomes:
measure: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 2, 4, 8 and 12
timeFrame: Baseline, Weeks 2, 4, 8 and 12
measure: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 2, 4, 8 and 12
timeFrame: Baseline, Weeks 2, 4, 8 and 12
measure: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis at Weeks 2, 4, 8 and 12
timeFrame: Baseline, Weeks 2, 4, 8 and 12
measure: Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis at Week 24
timeFrame: Baseline, Week 24
measure: Percentage of Participants Meeting Outcomes Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) Responder Index
timeFrame: Weeks 2, 4, 8, 12, 16 and 24
measure: Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Reduction >= 30 Percent (%), >=50%, >=70% and >=90% Response
timeFrame: Week 2, 4, 8, 12, 16 and 24
measure: Percentage of Participants With Cumulative Percent Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Week 16
timeFrame: Baseline to Week 16
measure: Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Reduction >= 30 Percent (%), >=50%, >=70% and >=90% Response
timeFrame: Weeks 2, 4, 8, 12, 16 and 24
measure: Percentage of Participants With Cumulative Percent Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Week 16
timeFrame: Baseline to Week 16
measure: Percentage of Participants Achieving Improvement of >=2 Points in Patient's Global Assessment (PGA) of Osteoarthritis
timeFrame: Weeks 2, 4, 8, 12, 16 and 24
measure: Change From Baseline for Average Pain Score in the Index Joint at Weeks 1, 2, 3, 4, 6, 8, 10, 12 and 16
timeFrame: Baseline, Weeks 1, 2, 3, 4, 6, 8, 10, 12 and 16
measure: Change From Baseline for Average Pain Score in the Index Joint at Weeks 20 and 24
timeFrame: Baseline, Weeks 20 and 24
measure: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale at Weeks 2, 4, 8, 12 and 16
timeFrame: Baseline, Weeks 2, 4, 8, 12 and 16
measure: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Weeks 2, 4, 8, 12 and 16
timeFrame: Baseline, Weeks 2, 4, 8, 12 and 16
measure: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item (Pain When Walking on a Flat Surface) at Weeks 2, 4, 8, 12 and 16
timeFrame: Baseline, Weeks 2, 4, 8, 12 and 16
measure: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item (Pain When Walking on a Flat Surface) at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale (Pain When Going up or Down Stairs) at Weeks 2, 4, 8, 12 and 16
timeFrame: Baseline, Weeks 2, 4, 8, 12 and 16
measure: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale (Pain When Going up or Down Stairs) at Week 24
timeFrame: Baseline, Week 24
measure: Work Productivity and Activity Impairment Questionnaire for Osteoarthritis (WPAI:OA) Scores at Baseline
timeFrame: Baseline
measure: Change From Baseline in Work Productivity and Activity Impairment Questionnaire for Osteoarthritis (WPAI:OA) Scores at Week 16
timeFrame: Baseline and Week 16
measure: European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Dimensions Score
timeFrame: Baseline, Weeks 8 and 16
measure: European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Overall Health Utility Score/Index Value
timeFrame: Baseline, Weeks 8 and 16
measure: Health Care Resource Utilization (HCRU): Number of Visits of Services Directly Related to Osteoarthritis
timeFrame: Baseline, Weeks 24 and 40
measure: Health Care Resource Utilization (HCRU): Number of Participants Who Visited the Emergency Room Due to Osteoarthritis
timeFrame: Baseline, Weeks 24 and 40
measure: Health Care Resource Utilization (HCRU): Number of Visits to the Emergency Room Due to Osteoarthritis
timeFrame: Baseline, Weeks 24 and 40
measure: Health Care Resource Utilization (HCRU): Number of Participants Hospitalized Due to Osteoarthritis
timeFrame: Baseline, Weeks 24 and 40
measure: Health Care Resource Utilization (HCRU): Number of Nights Stayed in the Hospital Due to Osteoarthritis
timeFrame: Baseline, Weeks 24 and 40
measure: Health Care Resource Utilization (HCRU): Number of Participants Who Used Any Aids/Devices for Doing Things
timeFrame: Baseline, Weeks 24 and 40
measure: Health Care Resource Utilization (HCRU): Number of Participants Who Quit Job Due to Osteoarthritis
timeFrame: Baseline, Weeks 24 and 40
measure: Health Care Resource Utilization (HCRU): Duration Since Quitting Job Due to Osteoarthritis
timeFrame: Baseline, Weeks 24 and 40
measure: Number of Participants Who Withdrew Due to Lack of Efficacy
timeFrame: Baseline up to Week 16
measure: Time to Discontinuation Due to Lack of Efficacy
timeFrame: Baseline up to Week 16
measure: Number of Participants Who Took Rescue Medication During Weeks 2, 4, 8, 12 and 16
timeFrame: Week 2, 4, 8, 12 and 16
measure: Number of Participants Who Took Rescue Medication During Week 24
timeFrame: Week 24
measure: Number of Days of Rescue Medication Use at Week 2, 4, 8, 12 and 16
timeFrame: Week 2, 4, 8, 12, 16
measure: Number of Days of Rescue Medication Use at Week 24
timeFrame: Week 24
measure: Amount of Rescue Medication Taken at Weeks 2, 4, 8, 12 and 16
timeFrame: Week 2, 4, 8, 12, 16
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to Week 40
measure: Number of Participants With Treatment-Emergent Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to Week 40
measure: Number of Participants With Laboratory Test Abnormalities With Regard to Normal Baseline
timeFrame: Baseline up to Week 40
measure: Number of Participants With Laboratory Test Abnormalities With Regard to Abnormal Baseline
timeFrame: Baseline up to Week 40
measure: Change From Baseline in Blood Pressure (BP) at Weeks 2, 4, 8, 12, 16, 24, 40
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 24, 40
measure: Change From Baseline in Heart Rate at Weeks 2, 4, 8, 12,16, 24, 40
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 24 and 40
measure: Change From Baseline in Electrocardiogram (ECG) Parameters at Weeks 16 and 40
timeFrame: Baseline, Weeks 16, 40
measure: Change From Baseline in Heart Rate (as Assessed by ECG) at Weeks 16 and 40
timeFrame: Baseline, Weeks 16 and 40
measure: Percentage of Participants With Adjudicated Joint Safety Outcomes
timeFrame: Baseline up to Week 40
measure: Percentage of Participants With Total Joint Replacements
timeFrame: Baseline up to Week 40
measure: Change From Baseline in Neuropathy Impairment Score (NIS) at Weeks 2, 4, 8,12,16, 24 and 40
timeFrame: Baseline, Weeks 2, 4, 8,12,16, 24 and 40
measure: Number of Participants With Confirmed Orthostatic Hypotension
timeFrame: Baseline up to Week 40
measure: Change From Baseline in Survey of Autonomic Symptom (SAS) Scores at Weeks 24 and 40
timeFrame: Baseline, Weeks 24 and 40
measure: Number of Participants With Anti-Tanezumab Antibodies
timeFrame: Baseline, Weeks 8,16, 24 and 40
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Orthopaedic Surgeons
state: Alabama
city: Birmingham
country: United States
facility: Cahaba Research, Inc.
state: Alabama
city: Phoenix
country: United States
facility: Arizona Research Center
state: Arizona
city: Surprise
country: United States
facility: Clinical Research Institute of Arizona, LLC
state: Arizona
city: Tucson
country: United States
facility: Tucson Orthopaedic Institute
state: Arizona
city: Tucson
country: United States
facility: University of Arizona Clinical and Translational Science Research Center
state: Arizona
city: Little Rock
country: United States
facility: Baptist Health Center for Clinical Research
state: Arkansas
city: Anaheim
country: United States
facility: Advanced Research Center, Inc
state: California
city: Covina
country: United States
facility: Medvin Clinical Research
state: California
city: Fullerton
country: United States
facility: St. Jude Hospital Yorba Linda DBA St. Joseph Heritage Healthcare
state: California
city: Irvine
country: United States
facility: Irvine Center for Clinical Research
state: California
city: Irvine
country: United States
facility: Robert L Freed, M.D., F.A.C.R / Clinical Interventions Research Institute
state: California
city: North Hollywood
country: United States
facility: Providence Clinical Research
state: California
city: San Diego
country: United States
facility: Artemis Institute for Clinical Research
state: California
city: San Diego
country: United States
facility: California Research Foundation
state: California
city: Upland
country: United States
facility: Inland Rheumatology Clinical Trials, Inc.
state: California
city: Boulder
country: United States
facility: Alpine Clinical Research Center
state: Colorado
city: Bridgeport
country: United States
facility: New England Research Associates, LLC
state: Connecticut
city: Stamford
country: United States
facility: Stamford Therapeutics Consortium
state: Connecticut
city: Fort Myers
country: United States
facility: Clinical Physiology Associates
state: Florida
city: Hialeah
country: United States
facility: Eastern Research, Inc.
state: Florida
city: Miami
country: United States
facility: South Florida Research Center, Inc.
state: Florida
city: Miami
country: United States
facility: New Horizon Research Center
state: Florida
city: Miami
country: United States
facility: Miami Dade Medical Research Institute, LLC
state: Florida
city: Orlando
country: United States
facility: Compass Research, LLC
state: Florida
city: Ormond Beach
country: United States
facility: Ormond Beach Clinical Research
state: Florida
city: Tamarac
country: United States
facility: Phoenix Clinical Research, LLC
state: Florida
city: The Villages
country: United States
facility: Bioclinica Research
state: Florida
city: Atlanta
country: United States
facility: Atlanta Center for Medical Research
state: Georgia
city: Gainesville
country: United States
facility: Center for Advanced Research & Education (CARE)
state: Georgia
city: Honolulu
country: United States
facility: East-West Medical Research Institute
state: Hawaii
city: Chicago
country: United States
facility: Medex Healthcare Research Inc
state: Illinois
city: Chicago
country: United States
facility: Chicago Clinical Research Institute, Inc.
state: Illinois
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine
state: Illinois
city: Chicago
country: United States
facility: Great Lakes Clinical Trials
state: Illinois
city: Brownsburg
country: United States
facility: Investigators Research Group, LLC
state: Indiana
city: West Des Moines
country: United States
facility: Integrated Clinical Trial Services, Inc.
state: Iowa
city: Wichita
country: United States
facility: Professional Research Network of Kansas, LLC
state: Kansas
city: New Orleans
country: United States
facility: George Stanley Walker, MD
state: Louisiana
city: North Attleboro
country: United States
facility: Tristan Medical Enterprises, PC dba Regeneris Medical
state: Massachusetts
city: Rochester Hills
country: United States
facility: Michigan Orthopaedic & Spine Surgeons
state: Michigan
city: Flowood
country: United States
facility: Arthritis and Osteoporosis Treatment and Research Center
state: Mississippi
city: Las Vegas
country: United States
facility: Office Of Stephen H. Miller, M.D.
state: Nevada
city: Freehold
country: United States
facility: Arthritis And Osteoporosis Associates
state: New Jersey
city: Albuquerque
country: United States
facility: New Mexico Clinical Research & Osteoporosis Center, Inc.
state: New Mexico
city: Hartsdale
country: United States
facility: Drug Trials America
state: New York
city: Raleigh
country: United States
facility: Wake Research Associates, LLC
state: North Carolina
city: Fargo
country: United States
facility: Plains Clinical Research Center, LLC
state: North Dakota
city: Franklin
country: United States
facility: Prestige Clinical Research
state: Ohio
city: Tiffin
country: United States
facility: AC Clinical Research
state: Ohio
city: Oklahoma City
country: United States
facility: NPC Research
state: Oklahoma
city: Oklahoma City
country: United States
facility: Hillcrest Clinical Research
state: Oklahoma
city: State College
country: United States
facility: University Orthopedics Center
state: Pennsylvania
city: Greenville
country: United States
facility: Palmetto Clinical Trial Services, LLC
state: South Carolina
city: Rapid City
country: United States
facility: Health Concepts
state: South Dakota
city: Nashville
country: United States
facility: Quality Medical Research
state: Tennessee
city: Arlington
country: United States
facility: KRK Medical Research
state: Texas
city: Austin
country: United States
facility: Tekton Research, Inc
state: Texas
city: Baytown
country: United States
facility: Urgent Care MD's
state: Texas
city: Dallas
country: United States
facility: Arthritis Care and Diagnostic Center
state: Texas
city: Fort Worth
country: United States
facility: T&R Clinic, PA
state: Texas
city: Houston
country: United States
facility: Centex Studies, Inc.
state: Texas
city: Houston
country: United States
facility: BI Research Center
state: Texas
city: Plano
country: United States
facility: The Pain Relief Center
state: Texas
city: Chesapeake
country: United States
facility: Center for Arthritis and Rheumatic Diseases
state: Virginia
city: Danville
country: United States
facility: Spectrum Medical, Inc
state: Virginia
city: Richmond
country: United States
facility: National Clinical Research - Richmond, Inc
state: Virginia
city: Bellevue
country: United States
facility: Northwest Clinical Research Center
state: Washington
city: Brampton
country: Canada
facility: Aggarwal and Associates Limited
state: Ontario
city: Burlington
country: Canada
facility: Manna Research Inc. (Burlington south)
state: Ontario
city: Guelph
country: Canada
facility: Dawson Road Medical Centre
state: Ontario
city: Hamilton
country: Canada
facility: Adachi Medicine Professional Corporation
state: Ontario
city: Kitchener
country: Canada
facility: K-W Musculoskeletal Research Inc.
state: Ontario
city: London
country: Canada
facility: Western Center for Public Health and Family Medicine
state: Ontario
city: Mississauga
country: Canada
facility: Malton Medical Centre
state: Ontario
city: Oakville
country: Canada
facility: Rebecca Medical Associates
state: Ontario
city: Oshawa
country: Canada
facility: King Street Medical Clinic
state: Ontario
city: Sarnia
country: Canada
facility: Bluewater Clinical Research Group
state: Ontario
city: Montreal
country: Canada
facility: Diex Recheche Montreal, Inc.
state: Quebec
city: Quebec City
country: Canada
facility: Alpha Recherche Clinique
state: Quebec
city: Sherbrooke
country: Canada
facility: Diex Research Sherbrooke Inc.
state: Quebec
city: Quebec
country: Canada
facility: Recherche Clinique Sigma inc
city: Quebec
country: Canada
facility: Diex Recherche Quebec Inc.
city: Quebec
country: Canada
facility: G.R.M.O. (Groupe de recherche en maladies osseuses) Inc.
city: Quebec
country: Canada
facility: Centre de recherche Saint-Louis
city: Ponce
country: Puerto Rico
facility: Puerto Rico Medical Research Inc.
city: San Juan
country: Puerto Rico
facility: Mindful Medical Research
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.