RN624 In Adult Patients With Chronic Low Back Pain

PHASE II RANDOMIZED, DOUBLE-BLIND, PLACEBO-AND ACTIVE CONTROLLED, MULTICENTER, PARALLEL GROUP PROOF OF CONCEPT STUDY OF THE ANALGESIC EFFECTS OF RN624 IN ADULT PATIENTS WITH CHRONIC LOW BACK PAIN

The primary objective of this study is to evaluate the analgesic efficacy of RN624 compared with placebo and compared with naproxen in the treatment of adult patients with chronic low back pain.

Study Overview

• Status: Completed
• Conditions: Low Back Pain
• Intervention / Treatment: Drug: Naproxen; Drug: Placebo; Drug: PF-04383119 (RN624)

• Study Type: Interventional
• Enrollment (Actual): 220
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Pinnacle Research Group LLC
    • Birmingham, Alabama, United States, 35209
      • Radiant Research
  • Arizona
    • Chandler, Arizona, United States, 85225
      • Radiant Research - Phoenix Southeast
    • Scottsdale, Arizona, United States, 85251
      • Radiant Research
  • California
    • Anaheim, California, United States, 92801
      • Advanced Clinical Research Institute
    • San Diego, California, United States, 92121
      • University of California San Diego
  • Florida
    • DeFuniak Springs, Florida, United States, 32435
      • Doctors Medical center of Walton County
    • Destin, Florida, United States, 32541
      • SJS Clinical Research, Inc.
    • Longwood, Florida, United States, 32779
      • Adult Medicine Specialists
    • Longwood, Florida, United States, 32779
      • Genesis Research International
    • Naples, Florida, United States, 34102
      • Collier Neurologic Specialists
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Cotton-O'Neil Clinical Research
    • Topeka, Kansas, United States, 66606
      • Cotton-O'Neil Clinic
    • Wichita, Kansas, United States, 67207
      • Heartland Research Associates
  • Massachusetts
    • North Dartmouth, Massachusetts, United States, 02747
      • Northeast Medical Research Associates, Inc
    • Worcester, Massachusetts, United States, 01610
      • Clinical Pharmacology Study Group
  • Mississippi
    • Picayune, Mississippi, United States, 39466
      • Spence Medical Research
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Radiant Research, Inc.
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Quality Clinical Research, Inc.
  • New York
    • New York, New York, United States, 10024
      • The Medical Research Network, LLC
  • North Carolina
    • Lenoir, North Carolina, United States, 28645
      • North State Clinical Research, PLLC
    • Raleigh, North Carolina, United States, 27612
      • Wake Research Associates
    • Raleigh, North Carolina, United States, 27612
      • Wake Internal Medicine Consultants, Inc.
  • Oregon
    • Portland, Oregon, United States, 97210
      • Summit Research Network (Oregon), Inc.
  • Pennsylvania
    • Altoona, Pennsylvania, United States, 16602
      • Allegheny Pain Management
  • Rhode Island
    • Cranston, Rhode Island, United States, 02920
      • New England Center for Clinical Research
    • Cumberland, Rhode Island, United States, 02864
      • Partners in Clinical Research
    • Warwick, Rhode Island, United States, 02886
      • Omega Medical Research
  • South Carolina
    • Greer, South Carolina, United States, 29651
      • Radiant Research
  • Tennessee
    • Johnson City, Tennessee, United States, 37601
      • Advanced Therapeutics, Inc.
    • Johnson City, Tennessee, United States, 37601
      • Johnson City Internal Medicine
  • Texas
    • Bryan, Texas, United States, 77802
      • DiscoveResearch, Incorporated
    • Houston, Texas, United States, 77030
      • Advances in Health, Inc.
    • Nassau Bay, Texas, United States, 77058
      • Centex Research
    • Nassau Bay, Texas, United States, 77058
      • Immediate Medical Care
    • San Antonio, Texas, United States, 78229
      • Radiant Research San Antonio
  • Virginia
    • Virginia Beach, Virginia, United States, 23455
      • Independence Family Medicine
  • Washington
    • Seattle, Washington, United States, 98104
      • Summit Research Network (Seattle) Llc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female of any race, >18 years of age and have BMI ≤39 kg/m2
• Present with duration of chronic low back pain of ≥3 months requiring regular use of analgesic medication (>4 days per week for the past month)
• Primary location of low back pain is between the 12th thoracic vertebra and the lower gluteal folds, with or without radiation into the posterior thigh, classified as Category 1 or 2 according to the classification of the Quebec Task Force in Spinal Disorders
• Must have a score of ≥4 for Low Back Pain Intensity (NRS) while on current treatment at Screening, and completes at least 4 daily pain diaries during the 5 days prior to Randomization, with an average Low Back Pain Intensity (NRS) score of ≥4

Exclusion Criteria:

• Back pain due to visceral disorder (i.e. endometriosis) or Back pain due to recent major trauma (i.e. vertebral fracture, post-traumatic spondylolisthesis)
• History of lumbosacral radiculopathy, spinal stenosis associated with neurological impairment, or neurogenic claudication
• Osteoporotic compression fracture within the last 6 months
• Known history of: Rheumatoid arthritis; Seronegative spondyloarthropathy (i.e., ankylosing spondylitis, psoriatic arthritis, reactive arthritis, inflammatory bowel disease-related arthropathy); Paget's disease of spine, pelvis or femur; Fibromyalgia; Tumors or infections of the spinal cord
• Patients receiving acetaminophen only to manage their chronic low back pain
• Any uncontrolled or untreated chronic disease

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Single IV infusion of placebo on Day 1 and placebo for naproxen twice daily for Weeks 1-12.
Active Comparator: Naproxen	Drug: Naproxen; Oral naproxen 500 mg twice daily for Weeks 1-12.
Experimental: RN624	Drug: PF-04383119 (RN624); Single IV infusion of 200 micrograms/kg RN624 on Day 1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Daily Average Low Back Pain Intensity (LBPI) Score at Week 6	Daily average low back pain was assessed on an 11-point numeric rating scale (NRS). Participants described their average low back pain during the past 24 hours on a scale ranging from 0 (no pain) to 10 (worst possible pain). Baseline value was calculated as mean of the scores over 5-day prior to randomization (initial pain assessment period). Post-baseline weekly scores were calculated based on the mean of the scores over the 7 days prior to and including the day at the end of the corresponding week.	Baseline, Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Daily Average Low Back Pain Intensity (LBPI) Score at Week 1, 2, 4, 8 and 12	Daily average low back pain was assessed on an 11-point numeric rating scale (NRS). Participants described their average low back pain during the past 24 hours on a scale ranging from 0 (no pain) to 10 (worst possible pain), with lower scores indicating less pain. Baseline value was calculated as mean of the scores over 5-day prior to randomization (initial pain assessment period). Post-baseline weekly scores were calculated based on the mean of the scores over the 7 days prior to and including the day at the end of the corresponding week.	Baseline, Week 1, 2, 4, 8, 12
Change From Baseline in Average Low Back Pain Intensity (LBPI) Score Over Weeks 1 to 4, 1 to 8, 1 to 12, 5 to 8, and 5 to 12	Daily average low back pain was assessed on an 11-point numeric rating scale (NRS). Participants described their average low back pain during the past 24 hours on a scale ranging from 0 (no pain) to 10 (worst possible pain), with lower scores indicating less pain. Baseline value was calculated as mean of the scores over 5-day prior to randomization (initial pain assessment period). Post-baseline weekly scores were calculated based on the mean of the scores over the 7 days prior to and including the day at the end of the corresponding week. Change from baseline was calculated as the average of each specified week interval (Week 1 to 4, 1 to 8, 1 to 12, 5 to 8, 5 to 12) values minus the baseline value.	Baseline, Weeks 1 to 4, 1 to 8, 1 to 12, 5 to 8, 5 to 12
Change From Baseline in Modified Brief Pain Inventory-short Form (mBPI-sf) Scores for Worst Pain and Average Pain at Week 1, 2, 4, 6, 8 and 12	The mBPI-sf was a self-administered questionnaire used to assess the severity of pain and the impact of pain on daily functions during the 24-hour period prior to evaluation. It consisted of 5 questions. Questions (Q) 1-4 assessed the magnitude of pain (Q1 for worst pain, Q2 for least pain, Q3 for average pain, Q4 for pain right now) on an 11-point NRS ranging from 0 (no pain) to 10 (pain as bad as you can imagine), with lower scores indicating less pain. Question 5 consisted of 7 sub-items (A to G; general activity, mood, walking ability, normal work, relations with other people, sleep, enjoyment of life) which measured the level of interference of pain on daily functions. Each sub-item was assessed on an 11-point NRS ranging from 0 (does not interfere) to 10 (completely interferes). Results are reported for worst and average pain score, each ranging from 0 (no pain) to 10 (pain as bad as you can imagine), with lower scores indicating less pain.	Baseline, Week 1, 2, 4, 6, 8, 12
Number of Participants With Average Low Back Pain Intensity (LBPI) Score of 2 or Less	Daily average low back pain was assessed on an 11-point numeric rating scale (NRS). Participants described their average low back pain during the past 24 hours on a scale ranging from 0 (no pain) to 10 (worst possible pain), with lower scores indicating less pain. Weekly scores were calculated based on the mean of the scores over the 7 days prior to and including the day at the end of the corresponding week. Participants were classified as responders if average LBPI score was 2 or less, and as non-responders if average LBPI score was greater than (>) 2. Participants with average LBPI score of 2 or less were reported.	Week 1, 2, 4, 6, 8, 12
Number of Participants With Cumulative Percent (%) Reduction From Baseline in Average Low Back Pain Intensity (LBPI) Score at Week 6	Daily average low back pain was assessed on an 11-point numeric rating scale (NRS). Participants described their average low back pain during the past 24 hours on a scale ranging from 0 (no pain) to 10 (worst possible pain), with lower scores indicating less pain. Baseline value was calculated as mean of the scores over 5-day prior to randomization (initial pain assessment period). Post-baseline weekly scores were calculated based on the mean of the scores over the 7 days prior to and including the day at the end of the corresponding week. Number of participants with cumulative reduction (as percent) (greater than 0% ; >= 10, 20, 30, 40, 50, 60, 70, 80 and 90%; = 100 %) in Average LBPI score from Baseline at Week 6 were reported, participants (%) are reported more than once in categories specified.	Week 6
Number of Participants With at Least 30% and 50% Sustained Reduction From Baseline in Daily Average Low Back Pain Intensity (LBPI) Score	Daily average low back pain was assessed on an 11-point numeric rating scale (NRS). Participants described their average low back pain during the past 24 hours on a scale ranging from 0 (no pain) to 10 (worst possible pain) with lower scores indicating less pain. Baseline value was calculated as mean of the scores over 5-day prior to randomization (initial pain assessment period). Post-baseline weekly scores were calculated based on the mean of the scores over the 7 days prior to and including the day at the end of the corresponding week. Participants with >=30% or >=50% reduction from baseline in daily average LBPI score that was maintained for a minimum duration of 4 consecutive days were reported.	Week 12
Number of Participants With at Least 30% and 50% Reduction From Baseline in Daily Average Low Back Pain Intensity (LBPI) Score	Daily average low back pain was assessed on an 11-point numeric rating scale (NRS). Participants described their average low back pain during the past 24 hours on a scale ranging from 0 (no pain) to 10 (worst possible pain), with lower scores indicating less pain. Baseline value was calculated as mean of the scores over 5-day prior to randomization (initial pain assessment period). Post-baseline weekly scores were calculated based on the mean of the scores over the 7 days prior to and including the day at the end of the corresponding week. Number of participants with >=30% and >=50% reduction from Baseline in daily average LBPI score were reported.	Weeks 1, 2, 4, 6, 8, 12
Time to Achieve at Least 30% and 50% Sustained Reduction From Baseline in Daily Average Low Back Pain Intensity (LBPI) Score	Time to achieve >=30% or >=50% sustained reduction from baseline (i.e. reduction from baseline in daily average LBPI score that was maintained for a total of 4 consecutive days) was summarized using the Kaplan-Meier estimates of the median time to 30% and 50% response. Daily average low back pain was assessed on an 11-point numeric rating scale (NRS). Participants described their average low back pain during the past 24 hours on a scale ranging from 0 (no pain) to 10 (worst possible pain), with lower scores indicating less pain. Baseline value was calculated as mean of the scores over 5-day prior to randomization (initial pain assessment period). Post-baseline weekly scores were calculated based on the mean of the scores over the 7 days prior to and including the day at the end of the corresponding week.	Randomization to Last Study Visit (up to 16 weeks)
Total Duration of at Least 30% and 50% Reduction From Baseline in Daily Average Low Back Pain Intensity (LBPI) Score	Total duration of response was defined as the total number of days with >=30% or >=50% reduction from baseline in the daily average LBPI score. Daily average low back pain was assessed on an 11-point numeric rating scale (NRS). Participants described their average low back pain during the past 24 hours on a scale ranging from 0 (no pain) to 10 (worst possible pain), with lower scores indicating less pain. Baseline value was calculated as mean of the scores over 5-day prior to randomization (initial pain assessment period). Post-baseline weekly scores were calculated based on the mean of the scores over the 7 days prior to and including the day at the end of the corresponding week.	Week 1 up to Week 12
Change From Baseline in Roland-Morris Disability Questionnaire Total Score at Week 1, 2, 4, 6, 8, and 12	Roland-Morris Disability Questionnaire: low back pain-specific, participant administered questionnaire that assessed how well participants with low back pain were able to function with regard to daily activities. The questionnaire consisted of 24 statements and the participants were instructed to put a mark next to each appropriate statement if it described their pain on the day of assessment. The number of statements marked were added up by the clinician. Total RMDQ score was calculated as the sum of number of statements checked. Total possible score ranged from 0 to 24, with higher scores indicated greater disability.	Baseline, Week 1, 2, 4, 6, 8, 12
Change From Baseline in Modified Brief Pain Inventory-short Form (mBPI-sf) Scores for Pain Interference With Function (Composite Score), General Activity, Walking Ability, Normal Work and Sleep Scores at Week 1, 2, 4, 6, 8 and 12	The mBPI-sf was a self-administered questionnaire used to assess the severity of pain and the impact of pain on daily functions during the 24-hour period prior to evaluation. It consisted of 5 questions. Questions 1 to 4 assessed the magnitude of pain (worst, least, average, right now) on an 11-point NRS ranging from 0 (no pain) to 10 (pain as bad as you can imagine). Question 5 consisted of 7 sub-items (general activity [GA], mood, walking ability [WA], normal work [NW], relations with other people, sleep, enjoyment of life) which measured the level of interference of pain on daily functions. Each sub-item was assessed on an 11-point NRS ranging from 0 (did not interfere) to 10 (completely interfere). The response from 7 sub-items of question 5 were averaged to obtain pain interference composite score (CS), range: 0 to 10 (higher score=more interference).	Baseline, Week 1, 2, 4, 6, 8, 12
Number of Participants With Change From Baseline in Patient's Global Assessment of Low Back Pain (Disease Activity) Score at Week 1, 2, 4, 6, 8 and 12	Patient's global assessment of low back pain scale assessed participants overall impression of disease activity. Participants answered: "Considering all the ways your low back pain affects you, how are you doing today?" Participants responded using 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). Participants who reported a change of -4, -3, -2, -1, 0, 1, 2, 3, 4 from Baseline in Patient's Global Assessment of Low Back Pain (Disease Activity) score at specified weeks were presented.	Week 1, 2, 4, 6, 8, 12
Number of Participants With Each Response Level of Patient's Global Evaluation of Study Medication	Participants answered: "In all ways, how would you rate your overall response to the study medication today?" Participants responded using a 4-point Likert scale where 1 = poor, 2 = fair, 3 = good and 4 = excellent. Higher score indicated better overall response to the treatment.	Week 1, 2, 4, 6, 8, 12
Number of Participants Who Discontinued the Study Due to Lack of Efficacy		Baseline up to Week 12
Time to Discontinuation Due to Lack of Efficacy	Median time to discontinuation due to lack of efficacy was estimated using Kaplan-Meier method. Median was not estimable if the percentage of participants who discontinued due to lack of efficacy was below 50%.	Baseline up to Week 12
Number of Participants With Chronic Low Back Pain (CLBP) Response	Participants were considered as CLBP responders if they had achieved a reduction of >=30% in daily average LBPI score from baseline, an increase of >=30% in patient's global assessment of low back pain (disease activity) from baseline, and no worsening (increase) in RMDQ total score from baseline at specified week. Daily average low back pain assessed on an 11-point NRS ranging from 0 (no pain) to 10 (worst possible pain). Patient's global assessment of low back pain assessed using 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). RMDQ: low back pain-specific, participant administered questionnaire consisted of 24 statements and participants were instructed to put a mark next to each appropriate statement if it described their pain on the day of assessment. Total RMDQ score was calculated as sum of number of statements checked. Total possible score ranged from 0 to 24, with higher scores indicated greater disability.	Weeks 1, 2, 4, 6, 8, 12
Number of Participants Who Used Rescue Medications	In case of inadequate pain relief for CLBP or for non-CLBP related pain, acetaminophen up to 2000 mg per day up to 3 days per week could be taken as rescue medication. Number of participants with any use of rescue medication during the particular study week were summarized.	Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12
Duration of Rescue Medication Use	In case of inadequate pain relief for CLBP or for non-CLBP related pain, acetaminophen up to 2000 mg per day up to 3 days per week could be taken as rescue medication. The number of days of rescue medication use during the particular week were summarized.	Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12
Amount of Rescue Medication Taken	In case of inadequate pain relief for CLBP or for non-CLBP related pain, acetaminophen up to 2000 mg per day up to 3 days per week could be taken as rescue medication. The total dosage of acetaminophen (in mg) in each particular week was summarized.	Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (AEs) or 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 (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose (up to Week 16) that were absent before treatment or that worsened relative to pretreatment state.	Baseline up to 28 days after last dose of study treatment (up to Week 16)
Number of Participants With Anti-Drug Antibody (ADA)	Human serum anti-drug antibody (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 Week 12

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): July 5, 2007
• Primary Completion (Actual): September 2, 2008
• Study Completion (Actual): September 2, 2008

Study Registration Dates

• First Submitted: December 21, 2007
• First Submitted That Met QC Criteria: December 21, 2007
• First Posted (Estimate): January 2, 2008

Study Record Updates

• Last Update Posted (Actual): July 12, 2021
• Last Update Submitted That Met QC Criteria: June 17, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Back Pain; Low Back Pain; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Gout Suppressants; Tanezumab; Naproxen
• Other Study ID Numbers: A4091004; CLBP POC (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.