Clinical trial NCT00864097: Analgesic Efficacy And Safety of Tanezumab Added On To Diclofenac SR In Patients With Osteoarthritis Of The Knee Or Hip
Official title: A PHASE 3, RANDOMIZED, DOUBLE BLIND, CONTROLLED, MULTI CENTER STUDY OF THE ANALGESIC EFFICACY AND SAFETY OF TANEZUMAB ADDED ON TO DICLOFENAC SR IN PATIENTS WITH OSTEOARTHRITIS OF THE KNEE OR HIP
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Osteoarthritis
Keywords: Arthritis monoclonal antibody nerve growth factor (NGF) anti-NGF tanezumab PF-04383119 RN-624 OA
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2009-03-18
Enrollment: 607
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 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.

Detailed description: This study was terminated on 16 Nov 2010 following a US FDA clinical hold for tanezumab osteoarthritis clinical studies which halted dosing and enrollment of patients on 23 June 2010 for potential safety issues.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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).

Primary outcomes:
measure: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score at Week 16
timeFrame: Baseline, Week 16
measure: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Score at Week 16
timeFrame: Baseline, Week 16
measure: Change From Baseline in Patient Global Assessment (PGA) of Osteoarthritis Score at Week 16
timeFrame: Baseline, Week 16
Secondary outcomes:
measure: Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score at Weeks 2, 4, 8, 12 and 24
timeFrame: Baseline, Weeks 2, 4, 8, 12, and 24
measure: 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
timeFrame: Baseline, Weeks 2, 4, 8, 12, and 24
measure: Change From Baseline in Patient Global Assessment (PGA) of Osteoarthritis Score at Weeks 2, 4, 8, 12, and 24
timeFrame: Baseline, Weeks 2, 4, 8, 12, and 24
measure: Percentage of Participants With Outcome Measures in Rheumatology - Osteoarthritis Research Society International (OMERACT-OARSI) Response; LOCF
timeFrame: Weeks 2, 4, 8, 12, 16, and 24
measure: 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
timeFrame: Baseline, Week 16 and 24
measure: Percentage of Participants With At Least 30%, 50%, 70% and 90% Reduction From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score; LOCF
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, and 24
measure: Percentage of Participants With Improvement of at Least 2 Points in Patient Global Assessment (PGA) of Osteoarthritis; LOCF
timeFrame: Weeks 2, 4, 8, 12, 16, and 24
measure: Percentage of Participants With Improvement of at Least 2 Points in Patient Global Assessment (PGA) of Osteoarthritis; Baseline Observation Carried Forward (BOCF)
timeFrame: Weeks 2, 4, 8, 12, 16, and 24
measure: Change From Baseline in Average Pain Score in the Index Knee or Hip at Weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, and 24
timeFrame: Baseline, Weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, and 24
measure: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale Score at Weeks 2, 4, 8, 12, 16, and 24
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, and 24
measure: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Weeks 2, 4, 8, 12, 16, and 24
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, and 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, 16, and 24
timeFrame: Baseline, Week 2, 4, 8, 12, 16, 24
measure: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item: Pain When Going Up or Downstairs at Weeks 2, 4, 8, 12, 16, and 24
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, and 24
measure: Change From Baseline in 36-Item Short-Form Health Survey Version 2 (SF-36v2) Domain Scores at Week 12 and 24
timeFrame: Baseline, Week 12, and 24
measure: Change From Baseline in 36-Item Short-Form Health Survey Version 2 (SF-36v2) Physical and Mental Component Scores at Week 12 and 24
timeFrame: Baseline, Week 12 and 24
measure: Change From Baseline in European Quality of Life - 5 Dimension (EQ-5D) Index Score at Week 24
timeFrame: Baseline, Week 24
measure: Number of Participants With Change From Baseline in European Quality of Life - 5 Dimension (EQ-5D) Individual Health State Profile at Week 24
timeFrame: Baseline, Week 24
measure: Number of Participants Who Discontinued Due to Lack of Efficacy
timeFrame: Baseline up to end of study (Week 32)
measure: Time to Discontinuation (TTD) Due to Lack of Efficacy
timeFrame: Baseline up to Week 16 and 24
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to 112 days after last intravenous dose (up to Week 32)
Other outcomes:
measure: Number of Participants With Intravenous Doses of Study Medication
timeFrame: Day 1 up to Week 16
Locations:
city: Graz
country: Austria
facility: LKH-Medizinische Universitatsklinik Graz
city: Senftenberg
country: Austria
facility: Nuhr Zentrum
city: Wien
country: Austria
facility: ClinPharm International GmbH
city: Wien
country: Austria
facility: Medizinische Universitaet Wien/AKH
city: Wien
country: Austria
facility: Rheuma Zentrum Favoriten
city: Nantes cedex 1
country: France
facility: CHU de Nantes
city: Paris
country: France
facility: Hopital Lariboisiere
city: Berlin-Buch
country: Germany
facility: Viereck-Apotheke
city: Berlin
country: Germany
facility: Charité-Universitaetsmedizin Berlin
city: Berlin
country: Germany
facility: Klinische Forschung Berlin-Buch GmbH
city: Berlin
country: Germany
facility: Apotheke
city: Bochum
country: Germany
facility: Herz Apotheke
city: Bochum
country: Germany
facility: Synexus ClinPharm GmbH
city: Dresden
country: Germany
facility: Synexus ClinParm GmbH
city: Dresden
country: Germany
facility: Apotheke im Arztehaus Mickten
city: Goeppingen
country: Germany
facility: Schiller Apotheke & Stadt Apotheke
city: Goeppingen
country: Germany
facility: Schmerz- und Palliativzentrum Goeppingen
city: Hamburg
country: Germany
facility: Falken Apotheke Hoheluft
city: Hamburg
country: Germany
facility: Klinische Forschung Hamburg GmbH
city: Hannover
country: Germany
facility: Klinische Forschung Hannover - Mitte GmbH
city: Hannover
country: Germany
facility: Loewen-Apotheke
city: Leipzig
country: Germany
facility: Synexus ClinPharm GmbH
city: Leipzig
country: Germany
facility: Arkana Apotheke OHG
city: Magdeburg
country: Germany
facility: Synexus ClinPharm GmbH
city: Magdeburg
country: Germany
facility: Apotheke im MSZ
city: Potsdam
country: Germany
facility: Apotheke des Ernst von Bergmann Klinikums
city: Potsdam
country: Germany
facility: Synexus ClinParm GmbH
city: Potsdam
country: Germany
facility: Kirchsteig Apotheke
city: Chelm Slaski
country: Poland
facility: "Centrum Medyczne MEDENS S.C. Niepubliczny Zaklad
city: Krakow
country: Poland
facility: Malopolskie Centrum Medyczne s.c.
city: Warszawa
country: Poland
facility: Centrum Medyczne OSTEOMED Sp. z o. o.
city: Wroclaw
country: Poland
facility: Synexus SCM Sp. z o.o.
city: Zgierz
country: Poland
facility: Niepubliczny Zaklad Opieki Zdrowotnej "POLIMEDICA"
city: Ploiesti
country: Romania
facility: Municipal Hospital No. 1 "Schuller"
state: District Prahova
city: Bucharest
country: Romania
facility: Clinical Emergency Military Hospital "Dr. Carol Davila"
city: Bucharest
country: Romania
facility: Duo Medical srl
city: Bucharest
country: Romania
facility: Medical Center "SANA"
city: Bucharest
country: Romania
facility: Clinical Hospital "Sf. Maria"
city: Bucharest
country: Romania
facility: Center of Rheumatology "Dr Ion Stoia"
city: Constanta
country: Romania
facility: Clinical Emergency County Hospital Constanta
city: Galati
country: Romania
facility: County Emergency Clinic Hospital "Sf. Apostol Andrei"
city: Arkhangelsk
country: Russian Federation
facility: Center polyclinic of Federal State Institution
city: Moscow
country: Russian Federation
facility: State Healthcare Institution of Moscow city "City Clinical Hospital #15 n.a. O. M. Filatov"
city: Ryazan
country: Russian Federation
facility: Chair of Hospital Therapy of Ryazan State Medical University
city: St. Petersburg
country: Russian Federation
facility: St. Petersburg State Healthcare Institution "City Hospital #25 City Rheumatology Center"
city: St. Petersburg
country: Russian Federation
facility: State Educational Institution of Additional Professional Education
city: St. Petersburg
country: Russian Federation
facility: Institution of Russian Academy of Sciences "St. Petersburg Clinical Hospital of RAS"
city: St. Petersburg
country: Russian Federation
facility: St. Petersburg State Healthcare Institution "City Outpatient Clinical #51"
city: St. Petersburg
country: Russian Federation
facility: St. Petersburg State Healthcare Institution "City Pokrovskaya Hospital"
city: Santiago de Compostela
country: Spain
facility: Hospital Nuestra Señora de la Esperanza
state: A Coruna
city: Petrer
country: Spain
facility: Centro Salud Petrer 1
state: Alicante
city: Bilbao
country: Spain
facility: Hospital de Basurto
state: Vizcaya
city: Elda Alicante
country: Spain
facility: Hospital Comarcal de Elda
city: Getafe-Madrid
country: Spain
facility: Hospital Universitario Getafe
city: Madrid
country: Spain
facility: Hospital G. U. Gregorio Maranon
city: Santiago de Compostela
country: Spain
facility: Hospital Clinico Universitario Santiago
city: Goteborg
country: Sweden
facility: Me3plus AB
city: Goteborg
country: Sweden
facility: Me3plus AB
city: Malmo
country: Sweden
facility: Center for Lakemedelsstudier
city: Norrkoping
country: Sweden
facility: Medicinskt Centrum
city: Chernivtsi
country: Ukraine
facility: Chernivtsi Regional Clinical Hospital,Department of Rheumatology
city: Dnipropetrovsk
country: Ukraine
facility: Road Clinical Hospital at Dnipropetrovsk station, Department of Rheumatology
city: Donetsk
country: Ukraine
facility: Institute of Urgent and Recovery Surgery named after V.K. Gusaka AMS Ukraine
city: Donetsk
country: Ukraine
facility: Central City Clinical Hospital#1, Department of Therapy,
city: Ivano-Frankivsk
country: Ukraine
facility: Ivano-Frankivsk Regional Clinical Hospital
city: Kharkiv
country: Ukraine
facility: City Clinical Hospital #8, Department of reumatology,
city: Kiev
country: Ukraine
facility: State Institution "Institute of Gerontology AMS of Ukraine"
city: Kyiv
country: Ukraine
facility: Oleksandrivska Clinical Hospital in Kyiv-Department of Rheumatology # 1
city: Kyiv
country: Ukraine
facility: Kyiv Central Basin Clinical Hospital, Department of cardiology,
city: Lviv
country: Ukraine
facility: 4th City Communal Clinical Hospital, Department of Rheumatology,
city: Lviv
country: Ukraine
facility: City communal clinical hospital #5, Dept. of Therapy, Danylo Galytskiy Lviv National Med. University
city: Ternopil
country: Ukraine
facility: Communal Institution Ternopil regional council, "Ternopil Regional Clinical Hospital"
city: Vinnytsya
country: Ukraine
facility: Vinnytsya regional clinical hospital named after M.I. Pyrogova
city: Zaporizhzhia
country: Ukraine
facility: Communal institution "City Hospital #7", Department of Therapy,
city: Barnsley
country: United Kingdom
facility: Barnsley Hospital NHS Trust
state: South Yorkshire
city: Dudley, West Midlands
country: United Kingdom
facility: Department of Rheumatology
city: Wigan
country: United Kingdom
facility: Wrightington Hospital
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.