Safety And Efficacy Of Tanezumab In Patients With Chronic Pancreatitis

Study Overview
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Brief Summary
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Tanezumab is effective in reducing the pain associated with chronic pancreatitis.

Detailed Description
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On 23 Dec 2010 the FDA imposed a clinical halt for anti-NGF compounds due to safety reasons, ie, a case of osteonecrosis which occurred in relation to an anti-NGF compound of another company. All indications with the exception of Cancer Pain are affected resulting in termination of all studies in respective indications. Recruitment of Study A4091044 was stopped effective 27 Dec 2010. Two patients recruited so far did not receive further doses and were followed up for safety until LSLV on 22 Mar 2011.

Official Title
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A PHASE 2, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY OF THE ANALGESIC EFFICACY AND SAFETY OF TANEZUMAB IN PATIENTS WITH CHRONIC PANCREATITIS

Conditions
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Chronic Pancreatitis

Intervention / Treatment
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* Biological: Tanezumab
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult male or female Written informed consent Diagnosis of chronic pancreatitis based on imaging studies Persistent abdominal pain due to chronic pancreatitis Qualifying pain score during the pre-treatment period Willing to comply with study visit schedule and study requirements including for women of child-bearing potential or male patients with female partners of child-bearing potential, the use of 2 forms of birth control Exclusion Criteria: Pregnant women, lactating mothers, women suspected of being pregnant and women who wish to become pregnant during the course of the study Chronic pancreatitis as a complication of pancreatic cancer or acute pancreatic duct obstruction Pancreatic surgery, lithotripsy or endoscopist decompression within 3 months History of alcoholism (within 1 year of screening) or concurrent alcohol abuse History of cancer in the past years Significant cardiac disease within 6 months History, diagnosis or signs and symptoms of significant neurologic disease Disqualifying laboratory values including Hepatitis B or C, HIV and drug test Other medical condition that may interfere with study endpoints or safety of the patient as determined by the Investigator Known history of rheumatoid arthritis Avascular necrosis of the bone History of trauma to a major joint Evidence of osteoarthritis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tanezumab 20 mg<br> | Biological: Tanezumab<br>* single administration of tanezumab 20 mg sub-cutaneously<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* single administration of placebo to match tanezumab, sub-cutaneously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Average Chronic Pancreatitis Pain Intensity Score Over the Period From Week 1 to Week 8 | Daily average chronic pancreatitis pain is assessed with an 11-point Numeric Rating Scale (NRS) ranging from 0 (no pain) to 10 (worst possible pain). | Baseline, Week 1 to 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Average and Worst Chronic Pancreatitis Pain Intensity Score at Week 1, 2, 4, 6, 8, 12 and 16 | Daily average chronic pancreatitis pain and worst chronic pancreatitis pain are assessed with an 11-point NRS ranging from 0 (no pain) to 10 (worst possible pain). | Baseline, Week 1, 2, 4, 6, 8, 12, 16 | 
| Change From Baseline in Worst Chronic Pancreatitis Pain Intensity Score Over Week 1 to Week 8 Period | Daily average worst chronic pancreatitis pain is assessed with an 11-point NRS ranging from 0 (no pain) to 10 (worst possible pain). | Baseline, Week 1 to 8 | 
| Number of Participants With At Least 30 Percent (%), 50%, 70% and 90% Reduction From Baseline in Average and Worst Chronic Pancreatitis Pain Intensity Score | Daily average chronic pancreatitis pain and worst chronic pancreatitis pain are assessed with an 11-point NRS ranging from 0 (no pain) to 10 (worst possible pain). | Week 8 | 
| Number of Participants With Cumulative Reduction From Baseline in Average and Chronic Pancreatitis Pain Intensity Score | Daily average chronic pancreatitis pain and worst chronic pancreatitis pain are assessed with an 11-point NRS ranging from 0 (no pain) to 10 (worst possible pain). | Week 8 | 
| Change From Baseline in Brief Pain Inventory - Short Form (BPI-sf) Average and Worst Pain Score at Week 8 and 16 | BPI-sf is an 11-item self-report questionnaire that is designed to assess the severity and impact of pain on daily functions. BPI-sf are 4 questions that assess pain intensity (question 5 consists of 7 items that assess level of interference of pain on daily functions (general activity, mood, walking ability, normal work, relations with other people, sleep, enjoyment of life). Each item was answered on a scale ranging from 0 to 10; '0=No pain and 10=Pain as bad as you can imagine'. Measure were scored by item, with lower scores indicated less pain or pain interference. | Baseline, Week 8, 16 | 
| Change From Baseline in Brief Pain Inventory - Short Form (BPI-sf) Pain Interference Index and Pain Interference Score for General Activity, Walking Ability, Sleep and Normal Work at Week 8 and 16 | BPI-sf is an 11-item self-report questionnaire that is designed to assess the severity and impact of pain on daily functions. BPI-sf are 4 questions that assess pain intensity (worst, least, average, right now) and question 5 consisted of 7 items that assess level of interference of pain on daily functions (general activity, mood, walking ability, normal work, relations with other people, sleep, enjoyment of life). Each item was answered on a scale ranging from 0 to 10; '0=No pain and 10=Pain as bad as you can imagine'. Measure was scored by item, with lower score indicated less pain or pain interference. The 7 items in question 5 were averaged to obtain pain interference index, range: 0 to 10; higher score=greater impairment. | Baseline, Week 8, 16 | 
| Change From Baseline in Patient's Global Assessment (PGA) of Chronic Pancreatitis at Week 4, 8 and 16 | Patient's Global Assessment of Chronic Pancreatitis is a global evaluation that utilizes a 5-point Likert scale with a score of 1 being the best (Very Good) and a score of 5 being the worst (Very Poor) for the following question: Considering all the ways your chronic pancreatitis affects you, how are you doing today?. | Baseline, Week 4, 8, 12 | 
| Number of Participants With Improvement of Greater Than or Equal to 2 Points From Baseline in Patient's Global Assessment (PGA) of Chronic Pancreatitis | Patient's Global Assessment of Chronic Pancreatitis is a global evaluation that utilizes a 5-point Likert scale with a score of 1 being the best (Very Good) and a score of 5 being the worst (Very Poor) for the following question: Considering all the ways your chronic pancreatitis affects you, how are you doing today?. | Weeks 4, 8, 16 | 
| Number of Participants With Anti Drug Antibody |  | Baseline, Week 8, 16 | 
| Neuropathy Impairment Score (NIS) | NIS: 74-item questionnaire assesses muscle weakness, reflexes and sensation; scored separately for left, right limbs (37 items for each side). Components of muscle weakness (hip and knee flexion, hip and knee extension, ankle dorsiflexors, ankle plantar flexors, toe extensors, toe flexors) scored on scale 0 (normal) to 4 (paralysis), higher score=greater weakness. Components of reflexes (quadriceps femoris, triceps surae) and sensation (touch pressure, pin-prick, vibration, joint position) scored 0 = normal, 1= decreased, or 2 = absent. Total possible NIS score range 0-244, higher score=greater impairment. | Baseline and Weeks 2, 4, 8, 16 | 
| Number of Participants With Injection Site Reaction | Assessment of the injection site reactions were based on presence of erythema (redness), induration (swelling), ecchymosis (bruising), pruritus (itching) and pain that occurred after the injection had been administered (not related to pain of needle insertion). | Day 1 up to Week 16 | 
| Plasma Tanezumab Levels |  | Baseline (pre-dose), Week 2, 4, 8, 16 | 
| Serum Nerve Growth Factor (NGF) Levels |  | Baseline (pre-dose), Week 8, 16 | 
| Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was 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; persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 112 days after last dose that were absent before treatment or that worsened relative to pretreatment state. | Baseline up to 112 days after the dose of study medication (up to 113 days) | 
| Number of Participants With Clinically Significant Laboratory Abnormalities | Laboratory analysis included blood chemistry, hematology, urinalysis, pregnancy test, glycosylated hemoglobin levels (HbA1c levels) test and blood alcohol test. | Baseline up to Week 16 | 
| Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities | All standard intervals (PR, QRS, QT, QT interval corrected for heart rate using Fridericia's formula [QTcF], QT interval corrected for heart rate using Bazett's formula [QTcB], RR intervals and heart rate) were analyzed for ECG abnormalities. | Baseline up to Week 16 |