RN624 In Adult Patients With Chronic Low Back Pain

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Low Back Pain

Intervention / Treatment
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* Drug: Naproxen
* Drug: Placebo
* Drug: PF-04383119 (RN624)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 |