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

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2009-009318-41-SE
• Date of registration: 03/06/2009
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc., 235 East 42nd Street, New York, NY 10017
• Public 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
• Scientific 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
• Date of first enrolment: 01/07/2009
• Target sample size: 600
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-009318-41
• 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: no Placebo: yes Other: no

Countries of recruitment

Austria, France, Germany, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
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 knee or hip based on American College of Rheumatology criteria with a radiographic (X-ray) confirmation (a Kellgren-Lawrence x-ray grade of =2). X-rays taken within the last 12 months may be used for confirmation;

4. Patients must be experiencing some benefit from their current stable oral dose regimen of diclofenac 150 mg/day, be tolerating their diclofenac daily regimen and 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. Patients must have had some improvement in OA index joint pain but still require additional pain relief at Screening. Patients must remain on their pre-Screen oral diclofenac for at least the final 14 days of the Screening Period directly prior to the Baseline (Randomization/Day 1) Visit for an average of at least 5 or 7 days peer week (ie, minimum 70% compliance over the final 14 days). The 14 day run-in period may be extended within the Screening Period if necessary (note: the minimum 70% compliance must be maintained for this extended period);

5. To be eligible for this study, the patient must meet each of the following 3 criteria:
a. WOMAC Pain Subscale NRS =4 in the index knee or index hip at Screening and at Baseline;
b. WOMAC Physical Function Subscale NRS =4 in the index knee or index hip at Baseline;
c. Patient’s Global Assessment of Osteoarthritis must be “fair”, “poor” or “very poor” at Baseline;

6. Patients must be willing to discontinue all prohibited 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 the 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 de
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 of >39 kg/m2;

3. History of other disease that may involve the index 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;

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;

10. Diagnosis of a transient ischemic attack in the 6 months prior to Screening, diagnosis of stroke with residual deficits;

11. History, diagnosis, or signs and 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;

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 or any of its excipients or existence of a medical condition or use of concomitant medication for which the use of acetaminophen is contraindicated;

18. Resting, sitting systolic blood pressure (BP) =160 mm Hg or diastolic blood pressure =100 mm Hg Screening.

19. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =3.0 times the upper limit of normal, 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;

20. Presence of drugs of, other illegal drugs or marijuana in the urine toxicology screen obtained at Screening indicative of current or past infection;

21. Positive Hepatitis B, Hepatitis C, or human immunodeficiency virus tests at Screening indicative of current or past infection;

22. Oral or intramuscular corticosteroids within 30 days prior to the Initial Pain Assessment Period;

23. Intra-articular corticosteroid injection in the index knee or hip within 12 weeks, or to any other joint within 30 days, prior to the Initial Pain Assessment Period;

24. Intra-articular hyaluronic acid injection to the index knee or hip within 30 days prior to the Initial Pain Assessment Period;

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 should not be enrolled in the study.

26. Patients on lithium therapy with 30 days prior to Screening. Patients with a significant likelihood of requiring this medication should not be enrolled in the study.

27. Patients with known hypersensitivity to NSAIDs or cyclooxygenase inhibitors; history of asthma, urticaria or allergic-type reactions after taking aspirin or NSAIDs; allergy to sulfonamides;

28. Patients taking >325 mg/day of aspirin at Screening. Patients taking =325 mg aspirin for non-analgesic or non-arthritic reasons, at a stable dose for

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: RI624, RN624
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2.5-
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: RI624, RN624
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: RI624, RN624
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: Voltarol
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Diclofenac
CAS Number: 15307-86-5
Other descriptive name: 2-(2-(2,6-dichlorophenylamino)phenyl)acetic acid
Concentration unit: mg/g milligram(s)/gram
Concentration type: equal
Concentration number: 75-

Primary Outcome(s)

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

The 3 co-primary efficacy endpoints are:

- Change from Baseline to Week 24 in the WOMAC Pain subscale;
- Change from Baseline to Week 24 in the WOMAC Physical Function subscale;
- Change from Baseline to Week 24 in the Patient Global Assessment of Osteoarthritis.

Main Objective: Primary Objective:

Demonstrate superior efficacy of tanezumab 10 mg, 5 mg, and 2.5 mg administered IV every 8 weeks in combination with oral diclofenac SR 75 mg BID versus placebo administered IV every 8 weeks in combination with oral diclofenac SR 75 mg BID at Week 24.

Secondary Objective: Secondary Objective:

Evaluate safety of tanezumab 10 mg, 5 mg, and 2.5 mg administered IV every 8 weeks in combination with oral diclofenac SR 75 mg BID up to Week 32.

Secondary ID(s)

2009-009318-41-GB

A4091017