Safety Extension Study Of Tanezumab When Administered By Subcutaneous Injection To Patients With Osteoarthritis

A PHASE 3, MULTICENTER, RANDOMIZED, LONG TERM STUDY OF THE SAFETY OF THE SUBCUTANEOUS ADMINISTRATION OF TANEZUMAB IN PATIENTS WITH OSTEOARTHRITIS OF THE KNEE

An evaluation of the long term safety of tanezumab when administered by subcutaneous injection every 8 weeks for up to 64 weeks

Study Overview

• Status: Terminated
• Conditions: Osteoarthritis
• Intervention / Treatment: Biological: Tanezumab; Biological: Tanezumab; Biological: Tanezumab

Detailed Description

This study was terminated on 29 September 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.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • La Mesa, California, United States, 91942
      • Triwest Research Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Must have participated in specific Phase 3 parent study

Exclusion Criteria:

• Failed screening for parent study, pregnant women, lactating mothers

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tanezumab 5 mg	Biological: Tanezumab; Tanezumab 10 mg administered by subcutaneous injection every 8 weeks for up to 7 injections; Biological: Tanezumab; Tanezumab 5 mg administered by subcutaneous injection every 8 weeks for up to 7 injections; Biological: Tanezumab; Tanezumab 2.5 mg administered by subcutaneous injection every 8 weeks for up to 7 injections
Experimental: Tanezumab 10 mg	Biological: Tanezumab; Tanezumab 10 mg administered by subcutaneous injection every 8 weeks for up to 7 injections; Biological: Tanezumab; Tanezumab 5 mg administered by subcutaneous injection every 8 weeks for up to 7 injections; Biological: Tanezumab; Tanezumab 2.5 mg administered by subcutaneous injection every 8 weeks for up to 7 injections
Experimental: Tanezumab 2.5 mg	Biological: Tanezumab; Tanezumab 10 mg administered by subcutaneous injection every 8 weeks for up to 7 injections; Biological: Tanezumab; Tanezumab 5 mg administered by subcutaneous injection every 8 weeks for up to 7 injections; Biological: Tanezumab; Tanezumab 2.5 mg administered by subcutaneous injection every 8 weeks for up to 7 injections

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE is any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug, up to early termination (Day 107) that were absent before treatment in this study or that worsened relative to pretreatment state.	Baseline up to Early Termination (Day 107)
Number of Participants With Clinically Significant Laboratory Abnormalities	Laboratory examination included blood chemistry, hematology and urinalysis. Reported results were to include abnormal laboratory findings without regard to baseline abnormality.	Baseline up to Early Termination (Day 107)
Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities	Following parameters were analyzed for ECG abnormality: PR interval, QRS interval, QT interval, QT interval corrected using the Bazett's formula (QTcB), QT interval corrected using Fredericia's formula (QTcF), RR interval and heart rate (HR).	Baseline up to Early Termination (Day 107)
Number of Participants With Neurologic Examination Abnormalities	Neurologic examination assessed the strength of groups of muscles of the head and neck, upper limbs and lower limbs, deep tendon reflexes and sensation (tactile, vibration, joint position sense and pin prick) of index fingers and great toes.	Baseline up to Early Termination (Day 107)
Number of Participants With Anti-Drug (Tanezumab) Antibody (ADA)	Human serum ADA samples were analyzed for the presence or absence of anti-tanezumab antibodies by using the semi-quantitative enzyme-linked immunosorbent assay (ELISA).	Baseline up to Early Termination (Day 107)
Number of Participants With Injection Site Reactions	Injection site reactions included: erythema (redness), induration (swelling), ecchymosis (bruising), pruritus (itching) and pain that occurred after the injection has been administered.	Baseline up to Early Termination (Day 107)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score at Week 4, 8, 16, 24, 32, 40, 48, 56, and 64	The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index joint in the past 48 hours. It is calculated as the mean of the scores from the 5 individual questions scored on a numerical rating scale (NRS) of 0 to 10, where higher scores indicated higher pain. Total score range for WOMAC pain subscale score is 0 to 10, where higher scores indicated higher pain.	Baseline, Week 4, 8, 16, 24, 32, 40, 48, 56, 64
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Score at Week 4, 8, 16, 24, 32, 40, 48, 56, and 64	The WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in the index joint in the past 48 hours. It is calculated as the mean of the scores from the 17 individual questions scored on a NRS of 0 to 10, where higher scores indicated worse function. Total score range for WOMAC physical function subscale score is 0 to 10, 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 4, 8, 16, 24, 32, 40, 48, 56, 64
Change From Baseline in Patient Global Assessment (PGA) of Osteoarthritis at Week 4, 8, 16, 24, 32, 40, 48, 56, and 64	PGA: Participants answered the following question: "Considering all the ways your osteoarthritis (OA) in your knee affects you, how are you doing today?" Participants rated their condition by using a 5-point Likert scale: 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).	Baseline, Week 4, 8, 16, 24, 32, 40, 48, 56, 64
Percentage of Participants With Outcome Measures in Rheumatoid Arthritis Clinical Trials - Osteoarthritis Research Society International (OMERACT-OARSI) Response	OMERACT-OARSI response: >=50 percent (%) improvement from baseline and absolute change from baseline of >=2 units at Week of interest in WOMAC pain or physical function subscale, or at least 2 of the following 3 being true: >=20% improvement from baseline and absolute change from baseline of >=1 unit at Week of interest in 1) WOMAC pain subscale, 2) WOMAC physical function subscale, 3) PGA of osteoarthritis (score: 1-5, higher score=more affected). WOMAC pain, physical function subscales assess amount of pain/difficulty experienced (score: 0-10, higher score=higher pain/difficulty).	Baseline, Week 4, 8, 16, 24, 32, 40, 48, 56, 64
Percentage of Participants With At Least 30 Percent (%), 50%, 70% and 90% Reduction in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score	The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index joint in the past 48 hours. It was calculated as the mean of the scores from the 5 individual questions scored on a numerical rating scale (NRS) of 0 to 10, where higher scores indicated higher pain. Total score range for WOMAC pain subscale score was 0 to 10, where higher scores indicated higher pain.	Baseline, Week 4, 8, 16, 24, 32, 40, 48, 56, 64
Number of Participants With Cumulative Reduction From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score	The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index joint in the past 48 hours. It was calculated as the mean of the scores from the 5 individual questions scored on a numerical rating scale (NRS) of 0 to 10, where higher scores indicated higher pain. Total score range for WOMAC pain subscale score was 0 to 10, where higher scores indicated higher pain.	Baseline, Week 4, 8, 16, 24, 32, 40, 48, 56, 64
Percentage of Participants With Improvement of At Least (>=) 2 Point in Patient Global Assessment (PGA) of Osteoarthritis	PGA: Participants answered the following question: "Considering all the ways your OA in your joint affects you, how are you doing today?" Participants rated their condition by using a 5-point Likert scale: 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).	Baseline, Week 4, 8, 16, 24, 32, 40, 48, 56, 64
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale Score at Week 4, 8, 16, 24, 32, 40, 48, 56, and 64	The WOMAC stiffness subscale is a 2-item questionnaire used to assess the amount of stiffness experienced in the index joint in the past 48 hours. It was calculated as the mean of the scores from the 2 individual questions scored on NRS of 0 to 10; where higher scores indicated more stiffness. Total score range for WOMAC stiffness subscale score is 0 to 10, where higher scores indicated more stiffness. Stiffness is defined as a sensation of decreased ease in movement of the index joint.	Baseline, Week 4, 8, 16, 24, 32, 40, 48, 56, 64
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Week 4, 8, 16, 24, 32, 40, 48, 56, and 64	WOMAC: self-administered, disease-specific 24-item questionnaire which assesses clinically important, participant-relevant symptoms for pain (5 items), stiffness (2 items) and physical function (17 items) in participants with osteoarthritis. WOMAC average score was the mean of WOMAC pain, physical function and stiffness subscale scores and ranges from 0 to 10, where higher score indicated worse response.	Baseline, Week 4, 8, 16, 24, 32, 40, 48, 56, 64
Change From Baseline in WOMAC Pain Subscale Item (Pain When Walking on a Flat Surface) at Week 4, 8, 16, 24, 32, 40, 48, 56, and 64	Participants answered: "How much pain have you had when walking on a flat surface?" Participants responded by using a NRS of 0 to 10, where 0 = no pain and 10 = extreme pain.	Baseline, Week 4, 8, 16, 24, 32, 40, 48, 56, 64
Change From Baseline in WOMAC Pain Subscale Item (Pain When Going Up or Down Stairs) at Week 4, 8, 16, 24, 32, 40, 48, 56, and 64	Participants answered: "How much pain have you had when going up or down stairs?" Participants responded by using a NRS of 0 to 10, where 0 = no pain and 10 = extreme pain.	Baseline, Week 4, 8, 16, 24, 32, 40, 48, 56, 64
Time to Discontinuation Due to Lack of Efficacy		Baseline up to Week 64
Number of Participants Who Received Concomitant Analgesic Medication for Osteoarthritis Treatment	Permissible concomitant analgesic medications included Food and Drug Administration (FDA) approved opioids, topical analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), capsaicin products, oral/injectable corticosteroids and viscosupplementation (for example, hyaluronan) and were to be prescribed as per investigator's discretion.	Baseline up to Day 107 (Early Termination)
Days Per Week of Concomitant Analgesic Medication Usage for Osteoarthritis Treatment	Permissible concomitant analgesic medications included Food and Drug Administration (FDA) approved opioids, topical analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), capsaicin products, oral/injectable corticosteroids and viscosupplementation (for example, hyaluronan) and were to be prescribed as per investigator's discretion.	Baseline up to Week 64
Tanezumab Plasma Concentration		Pre-dose on Week 8, 24, 40; Week 56, 64
Nerve Growth Factor (NGF) Serum Concentration	Serum samples were analyzed for determining total NGF concentration. Total NGF was analyzed using a validated, sensitive, and specific immune-affinity enrichment liquid chromatography tandem mass spectrometric (IA/LC/MS/MS) method.	Pre-dose on Week 8, 24, 40; Week 56, 64

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2010
• Primary Completion (Actual): September 29, 2010
• Study Completion (Actual): September 29, 2010

Study Registration Dates

• First Submitted: May 20, 2010
• First Submitted That Met QC Criteria: May 20, 2010
• First Posted (Estimate): May 21, 2010

Study Record Updates

• Last Update Posted (Actual): March 10, 2021
• Last Update Submitted That Met QC Criteria: March 3, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Tanezumab
• Other Study ID Numbers: A4091032; SAFETY EXTENSION OF 1027 (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.