Analgesic Efficacy And Safety of Tanezumab Added On To Diclofenac SR In Patients With Osteoarthritis Of The Knee Or Hip

NCT00864097 | Terminated Phase 3 Results DMC

• 3 other identifiers: A40910172009-009318-41P3 6 MO OA HIP/KNEE DICLOFENAC
• Study Type: interventional
• Target: 607
• Locations: 10 countries
• Sites: 77

Brief Summary

The purpose of this study is to investigate the analgesic efficacy and safety of tanezumab added on to diclofenac SR in patients with osteoarthritis of the knee or hip currently experiencing partial benefit from, and are tolerating, diclofenac 150 mg/day therapy.

Conditions

Osteoarthritis

Keywords

Arthritis monoclonal antibody nerve growth factor (NGF) anti-NGF tanezumab PF-04383119 RN-624 OA

Outcome Measures

Primary Outcomes (3)

• Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score 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 (OA). WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in index knee or hip during past 48 hours. It is calculated as mean of the scores from 5 individual questions, each scored on a numerical rating scale (NRS) of 0 (no pain) to 10 (extreme pain), where higher scores indicate higher pain. Total score range for WOMAC pain subscale score is 0 (no pain) to 10 (extreme pain), where higher scores indicate higher pain.

  Baseline, Week 16

• Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Score 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 OA. WOMAC physical function is a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in index knee or hip during past 48 hours. It is calculated as mean of the scores from 17 individual questions, each scored on a NRS of 0 (no difficulty) to 10 (extreme difficulty), where higher scores indicate worse function. Total score range for WOMAC physical function subscale score is 0 (no difficulty) to 10 (extreme difficulty), where higher scores indicate worse function. Physical function refers to participant's ability to move around and perform usual activities of daily living.

  Baseline, Week 16

• Change From Baseline in Patient Global Assessment (PGA) of Osteoarthritis Score at Week 16

  Participants answered: "Considering all the ways your osteoarthritis in your index joint (knee/hip) affects you, how are you doing today?" Participants responded by using a 5-point Likert scale, where 1 = very good (asymptomatic 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 which are intolerable and inability to carry out all normal activities). Higher score indicated worst condition.

  Baseline, Week 16

Secondary Outcomes (20)

• Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score at Weeks 2, 4, 8, 12 and 24

  Baseline, Weeks 2, 4, 8, 12, and 24

• Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Score at Weeks 2, 4, 8, 12, and 24

  Baseline, Weeks 2, 4, 8, 12, and 24

• Change From Baseline in Patient Global Assessment (PGA) of Osteoarthritis Score at Weeks 2, 4, 8, 12, and 24

  Baseline, Weeks 2, 4, 8, 12, and 24

• Percentage of Participants With Outcome Measures in Rheumatology - Osteoarthritis Research Society International (OMERACT-OARSI) Response; LOCF

  Weeks 2, 4, 8, 12, 16, and 24

• Percentage of Participants With Cumulative Reduction From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score at Week 16 and 24

  Baseline, Week 16 and 24

Other Outcomes (1)

• Number of Participants With Intravenous Doses of Study Medication

  Day 1 up to Week 16

Study Arms (4)

Tanezumab 10 mg + diclofenac

EXPERIMENTAL

IV tanezumab 10 mg every 8 weeks (through Week 16) and oral diclofenac SR 75 mg BID (through Week 32)

Biological: tanezumab; Drug: diclofenac

Tanezumab 5 mg + diclofenac

EXPERIMENTAL

IV tanezumab 5 mg every 8 weeks (through Week 16) and oral diclofenac SR 75 mg BID (through Week 32)

Biological: tanezumab; Drug: diclofenac

Tanezumab 2.5 mg + diclofenac

EXPERIMENTAL

IV tanezumab 2.5 mg every 8 weeks (through Week 16) and oral diclofenac SR 75 mg BID (through Week 32)

Biological: tanezumab; Drug: diclofenac

IV placebo + diclofenac

PLACEBO COMPARATOR

IV placebo to match tanezumab every 8 weeks (through Week 16) and oral diclofenac SR 75 mg BID (through Week 32)

Drug: diclofenac; Other: IV placebo

Interventions

tanezumab BIOLOGICAL

IV tanezumab 10 mg every 8 weeks (through Week 16)

Tanezumab 10 mg + diclofenac

diclofenac DRUG

Oral diclofenac SR 75 mg BID for 32 weeks

Tanezumab 10 mg + diclofenac

IV placebo OTHER

IV placebo to match tanezumab every 8 weeks (through Week 16)

IV placebo + diclofenac

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Osteoarthritis of the knee or hip according to ACR criteria with Kellgren-Lawrence X-ray grade equal to, or greater than, 2.
• Patients must be experiencing some benefit from their current stable dose regimen of oral diclofenac 150 mg/day and be tolerating their diclofenac regimen.
• Pain and function levels as required by the protocol at Screening and Baseline.
• Willing to discontinue all non-study pain medications throughout the study except as permitted per protocol.
• Willing and able to comply with lifestyle guidelines, scheduled visits, treatment plan, laboratory tests and other study procedures.

You may not qualify if:

• Pregnant women.
• BMI greater than 39.
• History of other disease that may involve index knee or hip including inflammatory joint diseases, chrystalline disease (gout or pseudogout), endocrinopathies, metabolic joint diseases, lupus erythematosus, rheumatoid arthritis (RA), joint infections, neuropathic disorders, avascular necrosis, Paget's disease or tumors.
• Fibromyalgia, regional pain caused by lumbar or cervical compression with radiculopathy or other moderate to severe pain that may confound assessments or self-evaluation of the pain associated with OA.
• Signs and symptoms of clinically significant cardiac disease within 6 months prior to screening.
• Diagnosis or TIA within 6 months prior to screening or diagnosis of stroke with residual deficits that would preclude completion of required study activities.
• History, diagnosis , signs or symptoms of clinically significant neurological and/or psychiatric disease/disorder.
• At Screening: uncontrolled hypertension, hemoglobin A1c greater than or equal to 10%, ALT or AST greater than or equal to 3X upper limit of normal, creatinine exceeding 150 micro-mol/L in men or 133 micro-mol/L in women.
• Patients on warfarin or other coumadin anticoagulant therapy and/or lithium therapy within 30 days prior to Screening.
• Known hypersensitivity to NSAIDs (eg, diclofenac), cyclooxygenase inhibitors or paracetamol (acetaminophen).

Sponsors & Collaborators

• Pfizer: lead

Study Sites (77)

LKH-Medizinische Universitatsklinik Graz

Graz, A-8036, Austria

Location

Nuhr Zentrum

Senftenberg, 3541, Austria

Location

ClinPharm International GmbH

Vienna, A-1090, Austria

Location

Medizinische Universitaet Wien/AKH

Vienna, A-1090, Austria

Location

Rheuma Zentrum Favoriten

Vienna, A-1100, Austria

Location

CHU de Nantes

Nantes, 44093, France

Location

Hopital Lariboisiere

Paris, 75010, France

Location

Charité-Universitaetsmedizin Berlin

Berlin, 10117, Germany

Location

Klinische Forschung Berlin-Buch GmbH

Berlin, 13125, Germany

Location

Apotheke

Berlin, 13353, Germany

Location

Herz Apotheke

Bochum, 44787, Germany

Location

Synexus ClinPharm GmbH

Bochum, 44787, Germany

Location

Viereck-Apotheke

Buch, 13125, Germany

Location

Synexus ClinParm GmbH

Dresden, 01067, Germany

Location

Apotheke im Arztehaus Mickten

Dresden, 01127, Germany

Location

Schiller Apotheke & Stadt Apotheke

Göppingen, 73033, Germany

Location

Schmerz- und Palliativzentrum Goeppingen

Göppingen, 73033, Germany

Location

Falken Apotheke Hoheluft

Hamburg, 20253, Germany

Location

Klinische Forschung Hamburg GmbH

Hamburg, 20253, Germany

Location

Klinische Forschung Hannover - Mitte GmbH

Hanover, 30159, Germany

Location

Loewen-Apotheke

Hanover, 30159, Germany

Location

Synexus ClinPharm GmbH

Leipzig, 04103, Germany

Location

Arkana Apotheke OHG

Leipzig, 04315, Germany

Location

Synexus ClinPharm GmbH

Magdeburg, 39104, Germany

Location

Apotheke im MSZ

Magdeburg, 39112, Germany

Location

Apotheke des Ernst von Bergmann Klinikums

Potsdam, 14467, Germany

Location

Synexus ClinParm GmbH

Potsdam, 14467, Germany

Location

Kirchsteig Apotheke

Potsdam, 14480, Germany

Location

"Centrum Medyczne MEDENS S.C. Niepubliczny Zaklad

Chełm Śląski, 41-403, Poland

Location

Malopolskie Centrum Medyczne s.c.

Krakow, 31-510, Poland

Location

Centrum Medyczne OSTEOMED Sp. z o. o.

Warsaw, 02-256, Poland

Location

Synexus SCM Sp. z o.o.

Wroclaw, 50-088, Poland

Location

Niepubliczny Zaklad Opieki Zdrowotnej "POLIMEDICA"

Zgierz, 95-100, Poland

Location

Municipal Hospital No. 1 "Schuller"

Ploieşti, Prahova, 100337, Romania

Location

Clinical Emergency Military Hospital "Dr. Carol Davila"

Bucharest, 010225, Romania

Location

Duo Medical srl

Bucharest, 010584, Romania

Location

Medical Center "SANA"

Bucharest, 011025, Romania

Location

Clinical Hospital "Sf. Maria"

Bucharest, 011172, Romania

Location

Center of Rheumatology "Dr Ion Stoia"

Bucharest, 020985, Romania

Location

Clinical Emergency County Hospital Constanta

Constanța, 900591, Romania

Location

County Emergency Clinic Hospital "Sf. Apostol Andrei"

Galati, 800578, Romania

Location

Center polyclinic of Federal State Institution

Arkhangelsk, 163000, Russia

Location

State Healthcare Institution of Moscow city "City Clinical Hospital #15 n.a. O. M. Filatov"

Moscow, 111539, Russia

Location

Chair of Hospital Therapy of Ryazan State Medical University

Ryazan, 390026, Russia

Location

St. Petersburg State Healthcare Institution "City Hospital #25 City Rheumatology Center"

Saint Petersburg, 190068, Russia

Location

State Educational Institution of Additional Professional Education

Saint Petersburg, 191015, Russia

Location

Institution of Russian Academy of Sciences "St. Petersburg Clinical Hospital of RAS"

Saint Petersburg, 194017, Russia

Location

St. Petersburg State Healthcare Institution "City Outpatient Clinical #51"

Saint Petersburg, 196211, Russia

Location

St. Petersburg State Healthcare Institution "City Pokrovskaya Hospital"

Saint Petersburg, 199106, Russia

Location

Hospital Nuestra Señora de la Esperanza

Santiago de Compostela, A Coruna, 15705, Spain

Location

Centro Salud Petrer 1

Petrel, Alicante, 03610, Spain

Location

Hospital de Basurto

Bilbao, Vizcaya, 48013, Spain

Location

Hospital Comarcal de Elda

Elda Alicante, 03600, Spain

Location

Hospital Universitario Getafe

Getafe-Madrid, 28905, Spain

Location

Hospital G. U. Gregorio Maranon

Madrid, 28007, Spain

Location

Hospital Clinico Universitario Santiago

Santiago de Compostela, 15706, Spain

Location

Me3plus AB

Gothenburg, 400 14, Sweden

Location

Me3plus AB

Gothenburg, 412 63, Sweden

Location

Center for Lakemedelsstudier

Malmo, 211 52, Sweden

Location

Medicinskt Centrum

Norrköping, 602 32, Sweden

Location

Chernivtsi Regional Clinical Hospital,Department of Rheumatology

Chernivtsi, 58000, Ukraine

Location

Road Clinical Hospital at Dnipropetrovsk station, Department of Rheumatology

Dnipropetrovsk, 49008, Ukraine

Location

Institute of Urgent and Recovery Surgery named after V.K. Gusaka AMS Ukraine

Donetsk, 83045, Ukraine

Location

Central City Clinical Hospital#1, Department of Therapy,

Donetsk, 83114, Ukraine

Location

Ivano-Frankivsk Regional Clinical Hospital

Ivano-Frankivsk, 76018, Ukraine

Location

City Clinical Hospital #8, Department of reumatology,

Kharkiv, 61176, Ukraine

Location

State Institution "Institute of Gerontology AMS of Ukraine"

Kiev, 04114, Ukraine

Location

Oleksandrivska Clinical Hospital in Kyiv-Department of Rheumatology # 1

Kyiv, 01023, Ukraine

Location

Kyiv Central Basin Clinical Hospital, Department of cardiology,

Kyiv, 04053, Ukraine

Location

4th City Communal Clinical Hospital, Department of Rheumatology,

Lviv, 79011, Ukraine

Location

City communal clinical hospital #5, Dept. of Therapy, Danylo Galytskiy Lviv National Med. University

Lviv, 79013, Ukraine

Location

Communal Institution Ternopil regional council, "Ternopil Regional Clinical Hospital"

Ternopil, 46001, Ukraine

Location

Vinnytsya regional clinical hospital named after M.I. Pyrogova

Vinnytsia, 21018, Ukraine

Location

Communal institution "City Hospital #7", Department of Therapy,

Zaporizhzhia, 69118, Ukraine

Location

Barnsley Hospital NHS Trust

Barnsley, South Yorkshire, S75 2EP, United Kingdom

Location

Department of Rheumatology

Dudley, West Midlands, DY1 2HQ, United Kingdom

Location

Wrightington Hospital

Wigan, WN6 9EP, United Kingdom

Location

Related Publications (3)

• Tive L, Bello AE, Radin D, Schnitzer TJ, Nguyen H, Brown MT, West CR. Pooled analysis of tanezumab efficacy and safety with subgroup analyses of phase III clinical trials in patients with osteoarthritis pain of the knee or hip. J Pain Res. 2019 Mar 19;12:975-995. doi: 10.2147/JPR.S191297. eCollection 2019.

  PMID: 30936738 DERIVED

• Hochberg MC, Tive LA, Abramson SB, Vignon E, Verburg KM, West CR, Smith MD, Hungerford DS. When Is Osteonecrosis Not Osteonecrosis?: Adjudication of Reported Serious Adverse Joint Events in the Tanezumab Clinical Development Program. Arthritis Rheumatol. 2016 Feb;68(2):382-91. doi: 10.1002/art.39492.

  PMID: 26554876 DERIVED

• Balanescu AR, Feist E, Wolfram G, Davignon I, Smith MD, Brown MT, West CR. Efficacy and safety of tanezumab added on to diclofenac sustained release in patients with knee or hip osteoarthritis: a double-blind, placebo-controlled, parallel-group, multicentre phase III randomised clinical trial. Ann Rheum Dis. 2014 Sep;73(9):1665-72. doi: 10.1136/annrheumdis-2012-203164. Epub 2013 Jul 12.

  PMID: 23852695 DERIVED

Related Links

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

MeSH Terms

Conditions

Osteoarthritis

Interventions

tanezumab; Diclofenac

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals

Limitations and Caveats

Due to United States Food and Drug Administration (FDA) imposed clinical hold, further study drug dosing was stopped prematurely and study was terminated.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

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: March 17, 2009
• First Posted: March 18, 2009
• Study Start: August 11, 2009
• Primary Completion: November 16, 2010
• Study Completion: November 24, 2010
• Last Updated: February 26, 2021
• Results First Posted: February 26, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will share

Locations

DE (21); AU (5); FR (2); RU (8); GB (3); SE (4); ES (7); RO (8); UA (14); PL (5)