A PHASE 3, MULTI-CENTER, RANDOMIZED, DOUBLE-BLIND, CONTROLLED STUDY OF THE LONG-TERM ANALGESIC EFFICACY AND SAFETY OF TANEZUMAB ALONE OR IN COMBINATION WITH NON-STEROIDAL ANTIINFLAMMATORY DRUGS (NSAIDS) VERSUS NSAIDS ALONE IN PATIENTS WITH OSTEOARTHRITIS OF THE KNEE OR HIP

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2008-004815-37-NL
• Date of registration: 29/12/2008
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc., 235 East 42nd Street, New York, NY 10017
• Public title: A PHASE 3, MULTI-CENTER, RANDOMIZED, DOUBLE-BLIND, CONTROLLED STUDY OF THE LONG-TERM ANALGESIC EFFICACY AND SAFETY OF TANEZUMAB ALONE OR IN COMBINATION WITH NON-STEROIDAL ANTIINFLAMMATORY DRUGS (NSAIDS) VERSUS NSAIDS ALONE IN PATIENTS WITH OSTEOARTHRITIS OF THE KNEE OR HIP
• Scientific title: A PHASE 3, MULTI-CENTER, RANDOMIZED, DOUBLE-BLIND, CONTROLLED STUDY OF THE LONG-TERM ANALGESIC EFFICACY AND SAFETY OF TANEZUMAB ALONE OR IN COMBINATION WITH NON-STEROIDAL ANTIINFLAMMATORY DRUGS (NSAIDS) VERSUS NSAIDS ALONE IN PATIENTS WITH OSTEOARTHRITIS OF THE KNEE OR HIP
• Date of first enrolment: 19/08/2009
• Target sample size: 2500
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-004815-37
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no

Countries of recruitment

Netherlands, Spain

Key inclusion & exclusion criteria

Inclusion criteria:
Patients must meet all of the following inclusion criteria to be eligible for enrollment into the study:

1. Patients must consent in writing to participate in the study by signing and dating an informed consent document indicating that the patient has been informed of all pertinent aspects of the study prior to completing any of the Screening procedures;

2. Male or female of any race, =18 years of age;

3. At Screening, patients must have a diagnosis of OA of the index joint (knee or hip) based on American College of Rheumatology criteria with radiographic (X-ray) confirmation (a Kellgren-Lawrence x-ray grade of =2).
4. Patients must be experiencing some benefit from their current stable dose regimen of oral NSAID therapy of either naproxen 1000 mg/day (either 500 mg BID or sustained release 1000 mg QD) or celecoxib 200 mg/day (either 100 mg BID or 200 mg QD), be tolerating their NSAID regimen, be taking this medication regularly (defined as an average of at least 5 days per week) during the 30 day period prior to the Screening Visit and must have had some improvement in OA index joint pain, but still requiring additional pain relief at Screening. Patients must remain on their pre-Screen oral NSAID of celecoxib or naproxen for at least the final 2 weeks of the Screening Period directly prior to the Baseline (Randomization / Day 1) Visit for an average of at least 5 of 7 days per week (ie, minimum 70% compliance);

5. To be eligible for this study, the patient must meet each of the following 3 criteria:

• WOMAC Pain subscale NRS =4 in the index knee or index hip at Screening and Baseline;
• WOMAC Physical Function subscale NRS =4 in the index knee or index hip at Baseline;
• Patient Global Assessment of Osteoarthritis must be “fair,” “poor,” or “very poor” at Baseline;

6. Patients must be willing to discontinue all non-study pain medications for OA except rescue medication and not use prohibited pain medications throughout the duration of the study except as permitted per Protocol.

7. Female patients must meet one of the following criteria:

a. Female patients of non-childbearing potential: post-menopausal, defined as women who are =45 years old with amenorrhea for 24 consecutive months (regardless of FSH levels); amenorrhea for at least 1 year AND have a serum Follicle-Stimulating Hormone (FSH) level greater than 30 IU/L at Screening; or surgically sterile, defined as having had a hysterectomy and/or bilateral oophorectomy;
b. Female patients of child-bearing potential: must not be pregnant or lactating and must be abstinent or use adequate contraception (2 forms of birth control, one of which must be a barrier method);
Women of childbearing potential must have a negative serum pregnancy test at Screening (within 30 days prior to Baseline) and a negative urine pregnancy test at Baseline prior to initial dosing.
Male patients must agree that they and their female spouses / partners will use adequate contraception (2 forms of birth control, one of which must be barrier method) or be of non-childbearing potential.
Females of child-bearing potential and males must be willing to use approved methods of contraception from commencement of Screening procedures until 16 weeks (112 days) after last dose of IV study medication. In the event of indeterminate or anomalous results on pregnancy/FSH testing or issues surrounding contraceptive requirements, Study Management should be contacted and will make the final decision as to the adequacy/ne
Exclusion criteria:
1. Pregnant women, lactating mothers, women suspected of being pregnant, and women who wish to be pregnant during the course of clinical study;

2. Body Mass Index (BMI) of >39 kg/m2;

3. History of other disease that may involve the index joint (knee or hip);

4. History of significant trauma or surgery to the index knee or hip within the previous year;

5. Planned surgical procedure during the duration of the study;

6. Largely or wholly incapacitated;

7. 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;

8. History of cancer within the last 5 years except for cutaneous basal cell or squamous cell cancer resolved by excision.

9. Signs and symptoms of clinically significant cardiac disease.
Patients with a history of heart block now controlled by a functioning cardiac pacemaker and/or transient episodes of asymptomatic tachy- or bradyarrhythmias are eligible.

10. Diagnosis of a transient ischemic attack in the 6 months prior to Screening, diagnosis of stroke with residual deficits that would preclude completion of required study activities.

11. History, diagnosis, signs or symptoms of clinically significant neurological disease.

12. History, diagnosis, signs or symptoms of any clinically significant psychiatric disorder.

13. Hospital admission for depression or suicide attempt within 5 years prior to Screening or presence at Screening of active severe major depression (determined from medical history or a score =15 on Patient Health Questionnaire [PHQ-9];

14. History of known alcohol, analgesic or drug abuse within 2 years of Screening;

15. Previous exposure to exogenous NGF or to an anti-NGF antibody;

16. History of allergic or anaphylactic reaction to a therapeutic or diagnostic monoclonal antibody or IgG-fusion protein;

17. History of intolerance or hypersensitivity to acetaminophen (paracetamol) or any of its excipients or existence of a medical condition or use of concomitant medication for which the use of acetaminophen (paracetamol) is contraindicated;

18. Resting, sitting systolic blood pressure >160 mm Hg or diastolic blood pressure >100 mm Hg at Screening;

19. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =3.0 times the upper limit of normal (ULN), or creatinine exceeding 1.7 mg/dL (150 µmol/L) in men or 1.5 mg/dL (133 µmol/L) in women, or hemoglobin A1c =10% at Screening. Repeat confirmatory tests may be performed;

20. Presence of drugs of abuse (including prescription medications without a valid prescription), other illegal drugs or marijuana in the urine toxicology screen obtained at Screening;

21. Positive Hepatitis B, Hepatitis C, or Human Immunodeficiency Virus (HIV) tests at Screening indicative of current or past infection;

22. Oral or intramuscular corticosteroids within 30 days prior to Baseline;

23. Intra-articular corticosteroids in the index knee or hip within 12 weeks or to any other joint within 30 days, prior to Baseline;

24. Intra-articular hyaluronic acid to the index knee or hip within 30 days prior to Baseline;

25. Patients on warfarin or other coumadin anticoagulant therapy within 30 days prior to Screening. Patients with a significant likelihood of requiring one of these medications;

26. Patients on lithium therapy within 30 days prior to Screening. Patients with a significant likelihood of requiring this medicatio

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

OSTEOARTHRITIS OF THE KNEE OR HIP
MedDRA version: 9.1 Level: LLT Classification code 10020108 Term: Hips osteoarthritis
MedDRA version: 9.1 Level: LLT Classification code 10023476 Term: Knee osteoarthritis

Intervention(s)

Product Name: Tanezumab
Product Code: PF-04383119
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Tanezumab
CAS Number: 880266-57-9
Current Sponsor code: PF-04383119
Other descriptive name: RN624, RI624
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Product Name: Tanezumab
Product Code: PF-04383119
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Tanezumab
CAS Number: 880266-57-9
Current Sponsor code: PF-04383119
Other descriptive name: RN624, RI624
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Trade Name: Celebrex
Product Name: Celecoxib
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Celecoxib
CAS Number: 169590-42-5
Other descriptive name: 4-[5-(4-methylphenyl)-3-(trifluoromethyl)
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Naproxen
Product Name: Naproxen
Pharmaceutical Form: Tablet
INN or Proposed INN: Naproxen
CAS Number: 22204-53-1
Other descriptive name: (+)-(S)-2-(6-methoxynaphthalen-2-yl)
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: Key Secondary Objectives

• Demonstrate the long-term safety of IV tanezumab 10 mg and 5 mg alone and in combination with an NSAID PO (naproxen 500 mg BID or celecoxib 100 mg BID) over 56 weeks of treatment;

• Demonstrate the efficacy of IV tanezumab 10 mg and 5 mg alone and in combination with an NSAID PO (naproxen 500 mg BID or celecoxib 100 mg BID) through Week 56.

Primary end point(s): Co-Primary Efficacy Endpoints

The three co-primary efficacy endpoints are:
• Change from Baseline to Week 16 in the Western Ontario and McMaster Universities Index (WOMAC) Pain subscale;

• Change from Baseline to Week 16 in the WOMAC Physical Function subscale;

• Change from Baseline to Week 16 in the Patient Global Assessment of Osteoarthritis.

Main Objective: Primary Objective

• Demonstrate superior efficacy of IV tanezumab 10 mg and 5 mg alone and in combination with an NSAID PO (naproxen 500 mg BID or celecoxib 100 mg BID) versus placebo in combination with an NSAID PO (naproxen 500 mg BID or celecoxib 100 mg BID) at Week 16.

Secondary ID(s)

A4091025