A PHASE 3 RANDOMIZED, DOUBLE-BLIND, ACTIVE-CONTROLLED, MULTICENTER STUDY OF THE LONG-TERM SAFETY AND EFFICACY OF SUBCUTANEOUS ADMINISTRATION OF TANEZUMAB IN SUBJECTS WITH OSTEOARTHRITIS OF THE HIP OR KNEE

• Register: EUCTR
• Last refreshed on: 16 December 2019
• Main ID: EUCTR2012-003721-22-SK
• Date of registration: 25/02/2016
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc
• Public title: A PHASE 3 RANDOMIZED, DOUBLE-BLIND, ACTIVE-CONTROLLED, MULTICENTER STUDY OF THE LONG-TERM SAFETY AND EFFICACY OF SUBCUTANEOUS ADMINISTRATION OF TANEZUMAB IN SUBJECTS WITH OSTEOARTHRITIS OF THE HIP OR KNEE
• Scientific title: A PHASE 3 RANDOMIZED, DOUBLE-BLIND, ACTIVE-CONTROLLED, MULTICENTER STUDY OF THE LONG-TERM SAFETY AND EFFICACY OF SUBCUTANEOUS ADMINISTRATION OF TANEZUMAB IN SUBJECTS WITH OSTEOARTHRITIS OF THE HIP OR KNEE
• Date of first enrolment: 22/04/2016
• Target sample size: 3000
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-003721-22
• 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: no Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Brazil, Bulgaria, Colombia, Croatia, Japan, Korea, Republic of, Lithuania, Mexico, New Zealand, Peru, Philippines, Russian Federation, Slovakia, Taiwan, Ukraine, United States

Contacts

• Name: ClinicalTrials.gov call Center
• Affiliation: Pfizer Inc

• Name: ClinicalTrials.gov call Center
• Affiliation: Pfizer Inc

Key inclusion & exclusion criteria

Inclusion criteria:
- Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study.
- Male or female of any race,>=18 years of age.
- A diagnosis of osteoarthritis of the index hip or knee based on American College of Rheumatology criteria with X-ray confirmation (a Kellgren-Lawrence X-ray Grade of >=2 as diagnosed by the Central Reader).
-Subjects must meet the following criteria pertaining to their osteoarthritis treatment regimen:
•Documented history indicating that acetaminophen therapy has not provided sufficient pain relief;
•Currently receiving a stable dose regimen of oral NSAID therapy consisting of one of the NSAIDs presented in the following table, be tolerating this NSAID 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):
Table 7. Qualifying Pre-study NSAID Treatment Regimens
NSAID Qualifying Dose Range
Naproxen 440 mg/day* to 1000 mg/day
Celecoxib 200 mg/day (either 100 mg BID or 200 mg QD)
Diclofenac 100 mg/day to 150 mg/day
Aceclofenac 200 mg/day
Loxoprofen 120 mg/day to 180 mg/day
Ibuprfen 1200 mg/day to 3200 mg/day
Meloxicam 5 mg/day to 15 mg/day
Nabumetone 1000 m/day to 2000 mg/day
Sulindac 200 mg/day to 400 mg/day
Ketoprofen 200 mg/day

•Maintain compliance with a stabilized dose regimen of either naproxen 500 mg BID, celecoxib 100 mg BID or diclofenac ER 75 mg BID (provided at Screening) with a minimum compliance of 70% (ie 5 of 7 days per week) for the final 2 or 3 weeks of the Screening period directly prior to the Baseline (Day 1) visit.
AND at least 1 of the following criteria:
•Documented history indicating that tramadol treatment has not provided adequate pain relief or subject is unable to take tramadol due to contraindication or inability to tolerate;
•Documented history indicating that opioid treatment has not provided adequate pain relief or subject is unwilling to take opioids, or unable to take opioids due to contraindication or inability to tolerate.
- WOMAC Pain subscale NRS >=5 in the index knee or index hip at Screening.
- Female subjects of childbearing potential and at risk for pregnancy must agree to use 2 highly effective methods of contraception throughout the study and for 112 days (16 weeks) after the last dose of assigned subcutaneous investigational product.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1950
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1050

Exclusion criteria:
- History or radiographic evidence of other diseases that could confound efficacy assessments (e.g., rheumatoid arthritis).
- History or radiographic evidence of orthopedic conditions that may increase the risk of, or confound assessment of joint safety conditions during the study.
- Planned surgical procedure during the duration of the study.
- A past history of carpal tunnel syndrome (CTS) with signs or symptoms of CTS in the one year prior to Screening.
- History of intolerance or hypersensitivity to the relevant oral NSAID (naproxen, celecoxib or diclofenac) the subject could be randomized to receive or any of its excipients or existence of a medical condition or use of concomitant medication for which the use of this NSAID is contraindicated (refer to product labeling).
- Signs and symptoms of clinically significant cardiac disease within 6 months of the study (e.g., unstable angina, myocardial infarction, resting bradycardia, poorly controlled or untreated hypertension) as defined in the protocol or subjects with any other cardiovascular illness that in the opinion of the Investigator would render a subject unsuitable to participate in the study or Subjects with a history of heart block requiring ongoing treatment of that is associated with symptoms.
- History, diagnosis, or signs and symptoms of clinically significant neurological disease (e.g., transient ischemic attack, stroke, peripheral or autonomic neuropathy) as specified in the protocol
- Subjects with evidence or symptoms consistent with autonomic dysfunction (e.g., orthostatic hypotension and/or autonomic symptoms) as defined in the protocol.


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

Health Condition(s) or Problem(s) studied

Osteoarthritis of the hip or knee
MedDRA version: 21.1 Level: LLT Classification code 10023476 Term: Knee osteoarthritis System Organ Class: 100000004859
MedDRA version: 21.1 Level: LLT Classification code 10020108 Term: Hips osteoarthritis System Organ Class: 100000004859

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Intervention(s)

Product Name: Tanezumab
Product Code: PF-04383119
Pharmaceutical Form: Solution for injection in pre-filled syringe
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 injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Product Name: Tanezumab
Product Code: PF-04383119
Pharmaceutical Form: Solution for injection in pre-filled syringe
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 injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

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

Product Name: Naproxen
Pharmaceutical Form: Tablet
INN or Proposed INN: Naproxen
CAS Number: 22204-53-1
Other descriptive name: Naproxen
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

Product Name: Diclofenac
Pharmaceutical Form: Modified-release capsule, hard
INN or Proposed INN: Diclofenac
CAS Number: 15307-86-5
Other descriptive name: Diclofenac
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 75-
Pharmaceutical form of the placebo: Modified-release capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: -Characterize the long-term joint safety risk using a composite endpoint (includes adjudication outcomes of rapidly progressive osteoarthritis (type-2 only), subchondral insufficiency fracture (or SPONK), primary osteonecrosis, or pathological fracture).
-Characterize the long-term risk of the following individual adjudication outcomes occurring: rapidly progressive osteoarthritis (type-1 only), rapidly progressive osteoarthritis (type-2 only), rapidly progressive osteoarthritis (type-1 or type-2 combined), subchondral insufficiency fracture (or SPONK), primary osteonecrosis,
and pathological fracture.

refer to protocol for further secondary objectives

Main Objective: - Characterize the long-term risk of joint safety events in subjects with osteoarthritis of the knee or hip who receive tanezumab 2.5 mg or tanezumab 5 mg SC versus NSAID treatment (naproxen 500 mg BID, celecoxib 100 mg BID, or diclofenac ER 75 mg BID) over the course of 56-weeks of treatment using a composite endpoint (includes adjudication outcomes of rapidly progressive osteoarthritis type-1 or type-2, subchondral insufficiency fracture (SPONK), primary osteonecrosis, or pathological fracture).

-Demonstrate superior efficacy of tanezumab 2.5 mg and tanezumab 5 mg SC versus NSAID treatment (naproxen 500 mg BID, celecoxib 100 mg BID, or diclofenac ER 75 mg BID) at Week 16.

Timepoint(s) of evaluation of this end point: Please refer to the protocol

Primary end point(s): Incidence of a predefined composite endpoint consisting of adjudication outcomes of rapidly progressive osteoarthritis (type-1 or type-2), subchondral insufficiency fracture (or SPONK), primary osteonecrosis, or pathological fracture (primary composite endpoint).

The co-primary efficacy endpoints are:

-Change from Baseline to Week 16 in the Western Ontario and McMaster Universities Osteoarthritis 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’s Global Assessment of Osteoarthritis.

Secondary Outcome(s)

Secondary end point(s): Bone and Joint Safety:
-Incidence of a predefined composite endpoint consisting of adjudication outcomes of rapidly progressive osteoarthritis (type-2 only), subchondral insufficiency fracture (or SPONK), primary osteonecrosis, or pathological fracture.
Refer to protocol for other Bone and Joint Safety endpoints

Radiographic:
-Change from Baseline to Week 56 and Week 80 in Medial or Lateral Minimum Joint
Space Width of the index knee (for subjects with Kellgren-Lawrence Grade 2 or 3 medial or lateral osteoarthritis of the index knee).
- Change from Baseline to Week 56 and Week 80 in Minimum Joint Space Width of the index hip (for subjects with Kellgren-Lawrence Grade 2 or 3 osteoarthritis of the index hip).
Refer to protocol for other Radiographic endpoints

Efficacy
-WOMAC Pain subscale change from Baseline to Weeks 2, 4, 8, 24, 32, 40, 48, 56 and Week 64.
-WOMAC Physical Function subscale change from Baseline to Weeks 2, 4, 8, 24, 32, 40, 48, 56 and Week 64.
- Patient’s Global Assessment of Osteoarthritis change from Baseline to Weeks 2, 4, 8, 16 (Japan only), 24, 32, 40, 48, 56 and Week 64.
-OMERACT-OARSI responder index at Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56 and Week 64.
-Treatment Response: Reduction in the WOMAC Pain subscale of >=30%, >=50%, >=70% and >=90% at Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56 and Week 64.
Refer to protocol for other Efficacy endpoints

Activity Level Monitoring
- Lower Extremity Activity Scale: change from Baseline to Weeks 4, 8, 16, 24, 56 and Week 80 (all subjects).
- Change from Baseline to Weeks 16 and 56 in average daily minutes of physical activity (a subset of subjects).
- Change from Baseline to Weeks 16 and 56 in average daily physical activity counts (a subset of subjects).
- Change from Baseline to Weeks 16 and 56 in average daily minutes of moderate to vigorous physical activity (a subset of subjects).
Refer to protocol for other Activity Level Monitoring endpoints

General Safety
-Adverse Events.
- Standard safety assessments (safety laboratory testing [chemistry, hematology], sitting vital signs, electrocardiogram (ECG; 12-lead).

Refer to protocol for other Safety endpoints

Timepoint(s) of evaluation of this end point: Please refer to the protocol

Secondary ID(s)

2012-003721-22-BG

A4091058

Source(s) of Monetary Support

Pfizer Inc, 235 East 42nd Street, New York, NY 10017

Ethics review

Status: Approved
Approval date:
Contact: