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

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.

Time frame: Baseline up to Early Termination (Day 107)

Population: ITT analysis population included all randomized participants who received at least 1 dose of study medication. Due to the US FDA imposed clinical hold, the study was terminated prematurely. Consequently, all planned analyses were not performed; data reported here is for baseline up to early termination (Day 107).

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).

Time frame: Baseline up to Early Termination (Day 107)

Population: ITT analysis population included all randomized participants who received at least 1 dose of study medication. Due to the US FDA imposed clinical hold, the study was terminated prematurely. Consequently, all planned analyses were not performed; data reported here is for baseline up to early termination (Day 107).

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).

Time frame: Baseline up to Early Termination (Day 107)

Population: ITT analysis population included all randomized participants who received at least 1 dose of study medication. Due to the US FDA imposed clinical hold, the study was terminated prematurely. Consequently, all planned analyses were not performed; data reported here is for baseline up to early termination (Day 107).

Laboratory examination included blood chemistry, hematology and urinalysis. Reported results were to include abnormal laboratory findings without regard to baseline abnormality.

Time frame: Baseline up to Early Termination (Day 107)

Population: ITT analysis population included all randomized participants who received at least 1 dose of study medication. Due to the US FDA imposed clinical hold, the study was terminated prematurely. Consequently, all planned analyses were not performed; data reported here is for baseline up to early termination (Day 107).

Injection site reactions included: erythema (redness), induration (swelling), ecchymosis (bruising), pruritus (itching) and pain that occurred after the injection has been administered.

Time frame: Baseline up to Early Termination (Day 107)

Population: ITT analysis population included all randomized participants who received at least 1 dose of study medication. Due to the US FDA imposed clinical hold, the study was terminated prematurely. Consequently, all planned analyses were not performed; data reported here is for baseline up to early termination (Day 107).

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.

Time frame: Baseline up to Early Termination (Day 107)

Population: ITT analysis population included all randomized participants who received at least 1 dose of study medication. Due to the US FDA imposed clinical hold, the study was terminated prematurely. Consequently, all planned analyses were not performed; data reported here is for baseline up to early termination (Day 107).

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).

Time frame: Baseline, Week 4, 8, 16, 24, 32, 40, 48, 56, 64

Population: ITT analysis population included all randomized participants who received at least 1 dose of study medication. Due to the US FDA imposed clinical hold, only 1 participant was enrolled and the study was terminated prematurely. Consequently, planned analyses for Week 8, 16, 24, 32, 40, 48, 56, and 64 were not performed.

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.

Time frame: Baseline, Week 4, 8, 16, 24, 32, 40, 48, 56, 64

Population: ITT analysis population included all randomized participants who received at least 1 dose of study medication. Due to the US FDA imposed clinical hold, only 1 participant was enrolled and the study was terminated prematurely. Consequently, planned analyses for Week 8, 16, 24, 32, 40, 48, 56, and 64 were not performed.

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.

Time frame: Baseline, Week 4, 8, 16, 24, 32, 40, 48, 56, 64

Population: ITT analysis population included all randomized participants who received at least 1 dose of study medication. Due to the US FDA imposed clinical hold, only 1 participant was enrolled and the study was terminated prematurely. Consequently, planned analyses for Week 8, 16, 24, 32, 40, 48, 56, and 64 were not performed.

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.

Time frame: Baseline, Week 4, 8, 16, 24, 32, 40, 48, 56, 64

Population: ITT analysis population included all randomized participants who received at least 1 dose of study medication. Due to the US FDA imposed clinical hold, only 1 participant was enrolled and the study was terminated prematurely. Consequently, planned analyses for Week 8, 16, 24, 32, 40, 48, 56, and 64 were not performed.

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.

Time frame: Baseline, Week 4, 8, 16, 24, 32, 40, 48, 56, 64

Population: ITT analysis population included all randomized participants who received at least 1 dose of study medication. Due to the US FDA imposed clinical hold, only 1 participant was enrolled and the study was terminated prematurely. Consequently, planned analyses for Week 8, 16, 24, 32, 40, 48, 56, and 64 were not performed.

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.

Time frame: Baseline, Week 4, 8, 16, 24, 32, 40, 48, 56, 64

Population: ITT analysis population included all randomized participants who received at least 1 dose of study medication. Due to the US FDA imposed clinical hold, only 1 participant was enrolled and the study was terminated prematurely. Consequently, planned analyses for Week 8, 16, 24, 32, 40, 48, 56, and 64 were not performed.

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.

Time frame: Baseline, Week 4, 8, 16, 24, 32, 40, 48, 56, 64

Population: ITT analysis population included all randomized participants who received at least 1 dose of study medication. Due to the US FDA imposed clinical hold, only 1 participant was enrolled and the study was terminated prematurely. Consequently, planned analyses for Week 8, 16, 24, 32, 40, 48, 56, and 64 were not performed.

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.

Time frame: Baseline up to Week 64

Population: Data not analyzed since no participant received concomitant analgesic medication.

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.

Time frame: Pre-dose on Week 8, 24, 40; Week 56, 64

Population: ITT analysis population included all randomized participants who received at least 1 dose of study medication. Due to the US FDA imposed clinical hold, the study was terminated prematurely (Day 107). Consequently, planned analyses for Week 24, 40, 56 and 64 were not performed.

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.

Time frame: Baseline up to Day 107 (Early Termination)

Population: ITT analysis population included all randomized participants who received at least 1 dose of study medication. Due to the US FDA imposed clinical hold, the study was terminated prematurely. Consequently, all planned analyses were not performed; data reported here is for baseline up to early termination (Day 107).

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.

Time frame: Baseline, Week 4, 8, 16, 24, 32, 40, 48, 56, 64

Population: Due to the US FDA imposed clinical hold, only 1 participant was enrolled and the study was terminated prematurely. Consequently, planned efficacy analysis was not performed.

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.

Time frame: Baseline, Week 4, 8, 16, 24, 32, 40, 48, 56, 64

Population: Due to the US FDA imposed clinical hold, only 1 participant was enrolled and the study was terminated prematurely. Consequently, planned efficacy analysis was not performed.

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).

Time frame: Baseline, Week 4, 8, 16, 24, 32, 40, 48, 56, 64

Population: Due to the US FDA imposed clinical hold, only 1 participant was enrolled and the study was terminated prematurely. Consequently, planned efficacy analysis was not performed.

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).

Time frame: Baseline, Week 4, 8, 16, 24, 32, 40, 48, 56, 64

Population: Due to the US FDA imposed clinical hold, only 1 participant was enrolled and the study was terminated prematurely. Consequently, planned efficacy analysis was not performed.

Time frame: Pre-dose on Week 8, 24, 40; Week 56, 64

Population: ITT analysis population included all randomized participants who received at least 1 dose of study medication. Due to the US FDA imposed clinical hold, the study was terminated prematurely (Day 107). Consequently, planned analyses for Week 24, 40, 56 and 64 were not performed.

Time frame: Baseline up to Week 64

Population: Data not analyzed since no participant discontinued the study due to lack of efficacy.