Efficacy and Safety of a Subcutaneous Tanezumab Titration Dosing Regimen in Subjects With Moderate to Severe Osteoarthritis of the Hip or Knee

NCT ID: NCT02697773

Last Updated: 2021-05-03

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

698 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-01-21

Study Completion Date

2018-05-14

Brief Summary

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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.

Detailed Description

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Conditions

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Osteoarthritis, Knee Osteoarthritis, Hip

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Placebo

placebo administered subcutaneously at day 0 and week 8

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

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.

Tanezumab 2.5 mg

tanezumab 2.5 mg administered subcutaneously at day 0 and week 8

Group Type EXPERIMENTAL

Tanezumab 2.5 mg

Intervention Type BIOLOGICAL

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.

Tanezumab 2.5mg/5mg

tanezumab 2.5 mg administered subcutaneously at day 0 and tanezumab 5 mg administered subcutaneously at week 8

Group Type EXPERIMENTAL

Tanezumab 2.5mg/5mg

Intervention Type BIOLOGICAL

Patient receives one dose of tanezumab 2.5 mg subcutaneously on Day 1 and one dose of tanezumab 5 mg subcutaneously at Week 8.

Interventions

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Placebo

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.

Intervention Type OTHER

Tanezumab 2.5 mg

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.

Intervention Type BIOLOGICAL

Tanezumab 2.5mg/5mg

Patient receives one dose of tanezumab 2.5 mg subcutaneously on Day 1 and one dose of tanezumab 5 mg subcutaneously at Week 8.

Intervention Type BIOLOGICAL

Other Intervention Names

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Titration Arm

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Pfizer

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Pfizer CT.gov Call Center

Role: STUDY_DIRECTOR

Pfizer

Locations

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Alabama Orthopaedic Surgeons

Birmingham, Alabama, United States

Site Status

Cahaba Research, Inc.

Birmingham, Alabama, United States

Site Status

Arizona Research Center

Phoenix, Arizona, United States

Site Status

Clinical Research Institute of Arizona, LLC

Surprise, Arizona, United States

Site Status

Tucson Orthopaedic Institute

Tucson, Arizona, United States

Site Status

University of Arizona Clinical and Translational Science Research Center

Tucson, Arizona, United States

Site Status

Baptist Health Center for Clinical Research

Little Rock, Arkansas, United States

Site Status

Advanced Research Center, Inc

Anaheim, California, United States

Site Status

Medvin Clinical Research

Covina, California, United States

Site Status

St. Jude Hospital Yorba Linda DBA St. Joseph Heritage Healthcare

Fullerton, California, United States

Site Status

Irvine Center for Clinical Research

Irvine, California, United States

Site Status

Robert L Freed, M.D., F.A.C.R / Clinical Interventions Research Institute

Irvine, California, United States

Site Status

Providence Clinical Research

North Hollywood, California, United States

Site Status

Artemis Institute for Clinical Research

San Diego, California, United States

Site Status

California Research Foundation

San Diego, California, United States

Site Status

Inland Rheumatology Clinical Trials, Inc.

Upland, California, United States

Site Status

Alpine Clinical Research Center

Boulder, Colorado, United States

Site Status

New England Research Associates, LLC

Bridgeport, Connecticut, United States

Site Status

Stamford Therapeutics Consortium

Stamford, Connecticut, United States

Site Status

Clinical Physiology Associates

Fort Myers, Florida, United States

Site Status

Eastern Research, Inc.

Hialeah, Florida, United States

Site Status

South Florida Research Center, Inc.

Miami, Florida, United States

Site Status

New Horizon Research Center

Miami, Florida, United States

Site Status

Miami Dade Medical Research Institute, LLC

Miami, Florida, United States

Site Status

Compass Research, LLC

Orlando, Florida, United States

Site Status

Ormond Beach Clinical Research

Ormond Beach, Florida, United States

Site Status

Phoenix Clinical Research, LLC

Tamarac, Florida, United States

Site Status

Bioclinica Research

The Villages, Florida, United States

Site Status

Atlanta Center for Medical Research

Atlanta, Georgia, United States

Site Status

Center for Advanced Research & Education (CARE)

Gainesville, Georgia, United States

Site Status

East-West Medical Research Institute

Honolulu, Hawaii, United States

Site Status

Medex Healthcare Research Inc

Chicago, Illinois, United States

Site Status

Chicago Clinical Research Institute, Inc.

Chicago, Illinois, United States

Site Status

Northwestern University Feinberg School of Medicine

Chicago, Illinois, United States

Site Status

Great Lakes Clinical Trials

Chicago, Illinois, United States

Site Status

Investigators Research Group, LLC

Brownsburg, Indiana, United States

Site Status

Integrated Clinical Trial Services, Inc.

West Des Moines, Iowa, United States

Site Status

Professional Research Network of Kansas, LLC

Wichita, Kansas, United States

Site Status

George Stanley Walker, MD

New Orleans, Louisiana, United States

Site Status

Tristan Medical Enterprises, PC dba Regeneris Medical

North Attleboro, Massachusetts, United States

Site Status

Michigan Orthopaedic & Spine Surgeons

Rochester Hills, Michigan, United States

Site Status

Arthritis and Osteoporosis Treatment and Research Center

Flowood, Mississippi, United States

Site Status

Office Of Stephen H. Miller, M.D.

Las Vegas, Nevada, United States

Site Status

Arthritis And Osteoporosis Associates

Freehold, New Jersey, United States

Site Status

New Mexico Clinical Research & Osteoporosis Center, Inc.

Albuquerque, New Mexico, United States

Site Status

Drug Trials America

Hartsdale, New York, United States

Site Status

Wake Research Associates, LLC

Raleigh, North Carolina, United States

Site Status

Plains Clinical Research Center, LLC

Fargo, North Dakota, United States

Site Status

Prestige Clinical Research

Franklin, Ohio, United States

Site Status

AC Clinical Research

Tiffin, Ohio, United States

Site Status

NPC Research

Oklahoma City, Oklahoma, United States

Site Status

Hillcrest Clinical Research

Oklahoma City, Oklahoma, United States

Site Status

University Orthopedics Center

State College, Pennsylvania, United States

Site Status

Palmetto Clinical Trial Services, LLC

Greenville, South Carolina, United States

Site Status

Health Concepts

Rapid City, South Dakota, United States

Site Status

Quality Medical Research

Nashville, Tennessee, United States

Site Status

KRK Medical Research

Arlington, Texas, United States

Site Status

Tekton Research, Inc

Austin, Texas, United States

Site Status

Urgent Care MD's

Baytown, Texas, United States

Site Status

Arthritis Care and Diagnostic Center

Dallas, Texas, United States

Site Status

T&R Clinic, PA

Fort Worth, Texas, United States

Site Status

Centex Studies, Inc.

Houston, Texas, United States

Site Status

BI Research Center

Houston, Texas, United States

Site Status

The Pain Relief Center

Plano, Texas, United States

Site Status

Center for Arthritis and Rheumatic Diseases

Chesapeake, Virginia, United States

Site Status

Spectrum Medical, Inc

Danville, Virginia, United States

Site Status

National Clinical Research - Richmond, Inc

Richmond, Virginia, United States

Site Status

Northwest Clinical Research Center

Bellevue, Washington, United States

Site Status

Aggarwal and Associates Limited

Brampton, Ontario, Canada

Site Status

Manna Research Inc. (Burlington south)

Burlington, Ontario, Canada

Site Status

Dawson Road Medical Centre

Guelph, Ontario, Canada

Site Status

Adachi Medicine Professional Corporation

Hamilton, Ontario, Canada

Site Status

K-W Musculoskeletal Research Inc.

Kitchener, Ontario, Canada

Site Status

Western Center for Public Health and Family Medicine

London, Ontario, Canada

Site Status

Malton Medical Centre

Mississauga, Ontario, Canada

Site Status

Rebecca Medical Associates

Oakville, Ontario, Canada

Site Status

King Street Medical Clinic

Oshawa, Ontario, Canada

Site Status

Bluewater Clinical Research Group

Sarnia, Ontario, Canada

Site Status

Diex Recheche Montreal, Inc.

Montreal, Quebec, Canada

Site Status

Recherche Clinique Sigma inc

Québec, Quebec, Canada

Site Status

Diex Recherche Quebec Inc.

Québec, Quebec, Canada

Site Status

G.R.M.O. (Groupe de recherche en maladies osseuses) Inc.

Québec, Quebec, Canada

Site Status

Centre de recherche Saint-Louis

Québec, Quebec, Canada

Site Status

Alpha Recherche Clinique

Québec, Quebec, Canada

Site Status

Diex Research Sherbrooke Inc.

Sherbrooke, Quebec, Canada

Site Status

Puerto Rico Medical Research Inc.

Ponce, PR, Puerto Rico

Site Status

Mindful Medical Research

San Juan, , Puerto Rico

Site Status

Countries

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United States Canada Puerto Rico

References

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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.

Reference Type DERIVED
PMID: 38650049 (View on PubMed)

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.

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PMID: 38343426 (View on PubMed)

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.

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PMID: 37982583 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37652258 (View on PubMed)

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.

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PMID: 37470295 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37460782 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36621827 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36474952 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36301512 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35980115 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35960482 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35232805 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35105318 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34626502 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33973384 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32252976 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31265100 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

Access external resources that provide additional context or updates about the study.

https://pmiform.com/clinical-trial-info-request?StudyID=A4091056

To obtain contact information for a study center near you, click here.

Other Identifiers

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2013-002222-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

OA TITRATION STUDY

Identifier Type: OTHER

Identifier Source: secondary_id

A4091056

Identifier Type: -

Identifier Source: org_study_id

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