An Efficacy And Safety Study Of Tanezumab For The Treatment Of Pain Associated With Chronic Abacterial Prostatitis

Study Overview
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Brief Summary
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The purpose of this study is to determine whether tanezumab is effective in the treatment of pain associated with chronic prostatitis.

Official Title
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A PHASE 2, 16 WEEK, MULTICENTER, RANDOMIZED, DOUBLE-BLIND PLACEBO-CONTROLLED, PARALLEL GROUP PROOF-OF-CONCEPT STUDY EVALUATING THE EFFICACY AND SAFETY OF TANEZUMAB FOR THE TREATMENT OF PAIN ASSOCIATED WITH CHRONIC ABACTERIAL PROSTATITIS

Conditions
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Chronic Prostatitis With Chronic Pelvic Pain Syndrome

Intervention / Treatment
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* Drug: Tanezumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of chronic prostatitis Male adults at least 18 years of age Moderate to severe chronic prostatitis, with an average pain score above a pre-defined level To use contraception. Exclusion Criteria: History of symptoms for less than 3 of the last 6 months History of recurrent urinary tract infections, or genito-urinary cancer Use of finasteride or dutasteride within 6 months. History of hepatitis B, C or human immunodeficiency virus (HIV)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

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<br> | Drug: Tanezumab<br>* Intravenous, 20 mg, single dose.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Intravenous placebo, single dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Average Daily Pain Score at Week 6 | Participants assessed average chronic prostatitis pain in the last 24 hours on an 11-point numeric rating scale (NRS) ranging from 0 (no chronic prostatitis pain) to 10 (chronic prostatitis pain as bad as you can imagine). The average daily pain score was calculated as the mean of the scores over the last 7 days prior to each assessment time point. Higher score indicated severe pain. | Baseline, Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Average Daily Pain Score at Weeks 2, 4, 8, 10, and 16 | Participants assessed average chronic prostatitis pain in the last 24 hours on an 11-point numeric rating scale (NRS) ranging from 0 (no chronic prostatitis pain) to 10 (chronic prostatitis pain as bad as you can imagine). The average daily pain score was calculated as the mean of the scores over the last 7 days prior to each assessment time point. Higher score indicated severe pain. | Baseline, Weeks 2, 4, 8, 10, and 16 | 
| Change From Baseline in Worst Daily Pain Score at Weeks 2, 4, 6, 8, 10, and 16 | Participants assessed worst chronic prostatitis pain in the last 24 hours on an 11-point numeric rating scale (NRS) ranging from 0 (no chronic prostatitis pain) to 10 (chronic prostatitis pain as bad as you can imagine). The worst daily pain score was calculated as the mean of the scores over the last 7 days prior to each assessment time point. Higher score indicated severe pain. | Baseline, Weeks 2, 4, 6, 8, 10, and 16 | 
| Change From Baseline in National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) Overall and Sub-scale Score at Weeks 2, 4, 6, 8, 10, and 16 | CPSI is a 9-item questionnaire, contains 3 modules that measure pain (question 1 to 4), urinary symptoms (question 5 and 6) and global quality of life (question 7 to 9). Total scores range from 0 to 21 on the pain module, 0 to 10 on the urinary symptoms and 0 to 12 on the quality of life module. NIH-CPSI total score (9-items) range from 0 to 43. Higher total and module scores indicate greater symptom severity and bother. | Baseline, Weeks 2, 4, 6, 8, 10, and 16 | 
| Change From Baseline in Number of Micturitions Per 24 Hours at Weeks 2, 4, 6, 8, 10, and 16 | The micturition frequency per 24 hours was calculated from the sum of voluntary voids divided by the diary period over which they were collected. | Baseline, Week 2, 4, 6, 8, 10, and 16 | 
| Change From Baseline in Number of Nocturnal Micturitions Per 24 Hours at Weeks 2, 4, 6, 8, 10, and 16 | Nocturnal micturition was calculated as the sum of voluntary voids that occur during a night's sleep, divided by the number of nights over which this was collected. | Baseline, Weeks 2, 4, 6, 8, 10, and 16 | 
| Change From Baseline in Mean Voided Volume Per Micturition at Weeks 2, 4, 6, 8, 10, and 16 | Mean voided volume per micturition was calculated as the total urine volume voided (resulting from a toilet [voluntary] void) during the diary period when this was measured, divided by the number of toilet voids over which this occurred. | Baseline, Weeks 2, 4, 6, 8, 10, and 16 | 
| Change From Baseline in Mean Urinary Event Pain Score Per 24 Hours at Weeks 2, 4, 6, 8, 10, and 16 | Subject assessed discrete urinary events: voluntary toilet voids (with volume voided), and urgency episodes. For each urinary event, subjects assessed the level of pain intensity on a 11-point numeric rating scale (NRS) ranging from 0 (no pain) to 10 (pain as bad as you can imagine). Mean pain severity per urinary event (toilet void, urgency episode) was calculated as the mean of all pain severities over the last 7 days prior to each assessment time point. Higher score indicated severe pain. | Baseline, Weeks 2, 4, 6, 8, 10, and 16 | 
| Change From Baseline in Urinary Urgency Episodes Per 24 Hours at Weeks 2, 4, 6, 8, 10, and 16 | Urinary urgency episodes per 24 hours was calculated as the sum of any urgency episodes occurring during the diary period when this was measured, divided by the number of days over which they were recorded. | Baseline, Weeks 2, 4, 6, 8, 10, and 16 | 
| Change From Baseline in Mean Sleep Disturbance Score Per 24 Hours at Weeks 2, 4, 6, 8, 10, and 16 | Mean sleep disturbance score was calculated from the sleep disturbance experienced over the previous night. The average sleep disturbance score per night was determined from calculating an average of all sleep disturbance scores in the 7 days prior to each assessment time point. Participants answered: Over the past 24 hours, how much did the symptoms that you associate with your chronic prostatitis disturb your sleep? Participants responded on a 5-points rating scale, ranged from 0 = not at all, 1 = a little, 2 = somewhat, 3 = very, and 4 = extremely. Higher score indicated greater sleep disturbance. | Baseline, Weeks 2, 4, 6, 8, 10, and 16 | 
| Change From Baseline in Mean Pain Score Associated With Ejaculation Per 24 Hours at Weeks 2, 4, 6, 8, 10, and 16 | The participants were first asked whether they had ejaculated during the past 24 hours. If yes, they recorded how much pain related to ejaculation they had experienced during the past 24 hours by choosing the appropriate number an 11-point numeric rating scale (NRS) ranging from 0 (no ejaculatory pain at all) to 10 (ejaculatory pain as bad as you can imagine). Higher score indicated greater pain. Mean pain score associated with ejaculation was calculated from all ejaculation pain scores recorded in the 7 days prior to each assessment time point. | Baseline, Weeks 2, 4, 6, 8, 10, and 16 | 
| Number of Participants With Global Response Assessment (GRA) | The GRA questionnaire is a 7-point symmetric scale, which measured patient-reported overall response to treatment compared to baseline with the following possible responses: 1= markedly worse, 2 = moderately worse, 3= slightly worse, 4= no change, 5 = slightly improved,6 = moderately improved, and 7 = markedly improved. Participants who reported either of the latter 2 categories were defined as treatment responders. Participants were asked Compared to when you began this trial, how would you rate your chronic prostatitis symptoms now?. Participants responded on 7-point symmetric scale ranged 1 to 7, where higher score indicated improvement. | Week 6 and 16 | 
| Patient Global Satisfaction Assessment | Participant global satisfaction was assessed using Patient Reported Treatment Impact (PRTI) which was a self-administered questionnaire containing four items to assess participant satisfaction, previous treatment, preference and willingness to continue using the study medication. Participant's answered the question Overall, how satisfied are you with the drug that you received since you entered this trial?. Participants provided response on a 5-point scale where 1=extremely dissatisfied, 2=dissatisfied, 3=neither satisfied nor dissatisfied, 4=satisfied and 5=extremely satisfied. Higher score indicated greater satisfaction, preference or willingness to use study medication. Number of participants with each response is reported. | Week 6 and 16 | 
| Participant Global Preference | Participant global preference is assessed using PRTI which is a self-administered questionnaire containing four items to assess participant satisfaction, previous treatment, preference and willingness to continue using the study medication. Participant reported previous treatment under following categories: lifestyle interventions, physical therapies, training programs, drug treatment - taken by mouth, surgery or other prostate procedure (e.g, microwave treatment), and no treatment. Participant preference was assessed using following categories: definitely prefer study medication, slightly prefer study medication, no preference, slightly prefer previous treatment, and definitely prefer previous treatment. Number of participants under each of the categories is reported. For previous treatment, a single participant may be represented in more than 1 category. | Week 6 and 16 | 
| Patient Willingness to Re-use Medicine | Participant willingness to re-use study medication was assessed using PRTI which is a self-administered questionnaire containing four items to assess participant satisfaction, previous treatment, preference and willingness to continue using the study medication. Participant willingness to re-use study medication was assessed using following categories: definitely want to re-use, might want to re-use, not sure, might not want to re-use, definitely would not want to re-use. | Week 6 and 16 | 
| Percentage of Participants Who Received Rescue Medication | In the event of inadequate pain relief or worsening symptoms of chronic prostatitis, participants were allowed to take acetaminophen/paracetamol 500 mg, tablets or capsules as rescue medication. | Weeks 2, 4, 6, 8, 10, and 16 | 
| Amount of Rescue Medication Taken | In the event of inadequate pain relief or worsening symptoms of chronic prostatitis, participants were allowed to take acetaminophen/paracetamol 500 mg, tablets or capsules as rescue medication. | Weeks 2, 4, 6, 8, 10, and 16 | 
| Serum and Urine Nerve Growth Factor (NGF) Levels | Serum NGF level was measured using Immunoaffinity High Performance Liquid Chromatography - Tandem Mass spectrometry (HPLC-MS/MS). | Day 1 (1 hour pre-dose), Weeks 2, 6, 10, and 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 medication 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 medication and up to Week 16 that were absent before treatment or that worsened relative to pretreatment state. AEs included SAEs as well as non-serious AEs which occurred during the trial. | Baseline up to Week 16 | 
| Number of Participants With Clinically Significant Neurological Examination Abnormalities | A neurological 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. | Baseline up to Week 16 | 
| Post-void Residual (PVR) Volume | PVR volume, an objective assessment of the amount of urine left in the bladder after normal urination and was monitored whether the active treatment had an adverse effect on lower urinary tract voiding function. The PVR volume was assessed using trans-abdominal ultrasound (e.g., bladder scanner) with the participant in a supine position immediately after voluntary urination. | Baseline, Weeks 2, 6, and 16 | 
| Number of Participants With Anti-Drug Antibody (ADA) | 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). | Day 1 (1 hour pre-dose), Weeks 2, 6, and 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Prostatis