Safety And Efficacy Of Tanezumab In Patients With Chronic Pancreatitis

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

Tanezumab is effective in reducing the pain associated with chronic pancreatitis.

Study Overview

• Status: Terminated
• Conditions: Chronic Pancreatitis
• Intervention / Treatment: Biological: Tanezumab; Other: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Naples, Florida, United States, 34102-5449
      • Gastroenterology Group-of Naples
    • Wellington, Florida, United States, 33414
      • Palm Beach Gastroenterology
  • Mississippi
    • Tupelo, Mississippi, United States, 38801
      • North Mississippi Medical Center
    • Tupelo, Mississippi, United States, 38801
      • Digestive Health Specialists
  • North Carolina
    • Harrisburg, North Carolina, United States, 28075
      • Carolinas Digestive Health Associates
    • Harrisburg, North Carolina, United States, 28705
      • Carolinas Digestive Health Associates
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
    • Pittsburgh, Pennsylvania, United States, 15213
      • UMPC Division of Radiology
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Wisconsin Center for Advanced Research

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:

• 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Subcutaneous Doses	Number of participants who received the single dose of placebo are reported.	Day 1

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): October 13, 2010
• Primary Completion (Actual): March 22, 2011
• Study Completion (Actual): March 22, 2011

Study Registration Dates

• First Submitted: May 24, 2010
• First Submitted That Met QC Criteria: June 16, 2010
• First Posted (Estimate): June 17, 2010

Study Record Updates

• Last Update Posted (Actual): March 23, 2021
• Last Update Submitted That Met QC Criteria: February 25, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pancreatic Diseases; Pancreatitis; Pancreatitis, Chronic; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Tanezumab
• Other Study ID Numbers: A4091044; 2010-019012-21 (EudraCT Number); CHRONIC PANCREATITIS POC STUDY (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.