RN624 For Pain Of Post-Herpetic Neuralgia

Study Overview
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Brief Summary
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This study will test the efficacy and safety of two doses levels of RN624 versus placebo for the relief of pain caused by post-herpetic neuralgia (PHN).

Official Title
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A PHASE II RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER, PARALLEL GROUP, PROOF OF CONCEPT STUDY OF THE ANALGESIC EFFECTS OF RN624 IN ADULT PATIENTS WITH POST-HERPETIC NEURALGIA

Conditions
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Neuralgia, Postherpetic

Intervention / Treatment
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* Drug: RN624
* Drug: RN624
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female of any race, at least 18 years of age. Patients must have pain present for more than 3 months after healing of the herpes zoster skin rash. Has a pain score at screening that qualifies. Completes at least 3 average daily pain diaries during the 3 days prior to randomization and has an average pain level that qualifies. Body Mass Index less than or equal to 39 kg/m2. If female, is post-menopausal, surgically sterile, or uses adequate contraception consisting of 2 forms of birth control, one of which must be barrier method, is not lactating, and is not breastfeeding. Male patients must agree that female spouses/partners will use contraception as defined above or be of nonchildbearing potential (post-menopausal or surgically sterile). Patients must be willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. Patients must consent in writing to participate in the study. Exclusion Criteria: Patients who cannot discontinue the use of other pain medications during the screening period and during the study. Disqualifying scores on questionnaires. Other moderate to severe pain from other conditions. History of allergic or anaphylactic reaction to antibodies. Use of biologics, including any live vaccines within 3 months of the week prior to the baseline visit. Unable to use acetaminophen. Disqualify laboratory values, Hepatitis B or C or HIV. Patients that have had a stroke or TIAs, dementia, epilepsy or seizures, or peripheral neuropathy from other conditions. Significant cardiac disease within 3 months of the study such as angina, heart attack, congestive heart failure, and other cardiac problems. Cancer other than basal cell or squamous cell carcinoma. Fails a urine test for illegal drugs including prescription drugs without a prescription. Plans for surgery during the study. History of alcoholism or drug abuse in the past two years. Surgery for post-herpetic neuralgia. Any condition that the investigator feels would put the safety of the patient at risk.

Ages Eligible for Study
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Minimum Age: 18 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: RN624<br>* 50 mcg/kg<br>|
| Active Comparator: 2<br> | Drug: RN624<br>* 200 mcg/kg<br>|
| Placebo Comparator: 3<br> | Drug: Placebo<br>* placebo<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 Numeric Rating Scale (NRS) Score at Week 6 | Participants assessed their average daily pain during the past 24 hours on an 11--point NRS ranging from 0 (no pain) to 10 (worst possible pain) with lower scores indicating less pain. Week 6 score was calculated as the mean of average daily pain NRS scores over the past 7 days. The change from baseline was calculated using difference between Week 6 mean score and Baseline mean score. | Baseline, Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Average Daily Pain Numeric Rating Scale (NRS) Score at Weeks 1, 2, 4, 8, 12 and 16 | Participants assessed their average daily pain during the past 24 hours on an 11--point NRS ranging from 0 (no pain) to 10 (worst possible pain) with lower scores indicating less pain. Post Baseline weekly scores were calculated as the mean of average daily pain NRS scores over the past 7 days prior to corresponding week visits. The change from baseline was calculated using difference between post baseline weekly mean score and the Baseline mean score. | Baseline, Week 1, 2, 4, 8, 12, 16 | 
| Change From Baseline in Average Daily Pain Numeric Rating Scale (NRS) Score Over Weeks 1 to 4, 1 to 8, 1 to 12, 1 to 16, 5 to 8, 5 to 12 and 5 to 16 | Participants assessed their average daily pain during the past 24 hours on an 11-point NRS ranging from 0 (no pain) to 10 (worst possible pain) with lower scores indicating less pain. Scores for each time interval over the weeks were calculated from the mean of daily pain score of participants over that specified duration. 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 and 5 to 16) values minus the baseline value. | Baseline, Week 1 to 4, Week 1 to 8, Week 1 to 12, Week 1 to 16, Week 5 to 8, Week 5 to 12, Week 5 to 16 | 
| Change From Baseline in Modified Brief Pain Inventory-Short Form (mBPI-sf) Scale Score for Worst Pain, Average Pain and Pain Severity at Weeks 1, 2, 4, 6, 8 ,12 and 16 | mBPI-sf is a self-administered questionnaire (5 questions) to assess pain severity and impact of pain on daily functions. Questions 1 to 4 measure the magnitude of pain (Q1 for worst, Q2 for least, Q3 for average and Q4 for pain right now) on an 11-point NRS ranging from 0 (no pain) to 10 (worst possible pain) with lower scores indicate less pain. Question 5 consists of 7 item subsets which measure the level of interference of pain on daily functions: 1: general activity, 2: mood, 3: walking ability, 4: normal work, 5: relations with other, 6: sleep, 7: enjoyment of life. Each item assessed on an 11-point NRS ranging from 0 (no interference) to 10 (complete interference), where lower scores indicate less interference of pain. Pain severity score was derived from the sum of responses of questions 1-4 and ranged from 0 (no pain) to 40 (worst possible pain) with lower scores indicates less pain. Results are reported for worst pain score, average pain score and pain severity score. | Baseline, Weeks 1, 2, 4, 6, 8 ,12, 16 | 
| Number of Participants With Mean Average Daily Pain Score of Less Than or Equal to (<=) 2 at Weeks 1, 2, 4, 6, 8, 12 and 16 | Participants assessed their average daily pain during the past 24 hours on an 11-point NRS ranging from 0 (no pain) to 10 (worst possible pain) with lower scores indicating less pain. Post-baseline weekly scores were calculated as the mean of average daily pain NRS scores over the past 7 days for each specified time point. Number of participants with average daily pain score of <=2 were reported. | Week 1, 2, 4, 6, 8, 12, 16 | 
| Number of Participants With Percent Reduction From Baseline in Average Daily Pain Score at Week 6 | Participants assessed their average daily pain during the past 24 hours on an 11-point NRS ranging from 0 (no pain) to 10 (worst possible pain) with lower scores indicating less pain. Week 6 score was calculated as the mean of average daily pain NRS scores over the past 7 days for each specified time point. Number of participants with specified percentage (%) of reduction in average daily pain scores from baseline at Week 6 were reported. Participants were counted more than once in different categories. | Baseline, Week 6 | 
| Number of Participants With at Least 30 Percent (%) and 50% Sustained Reduction From Baseline in Daily Average Pain Score at Week 6 | Participants assessed their average daily pain during the past 24 hours on an 11--point NRS ranging from 0 (no pain) to 10 (worst possible pain) with lower scores indicating less pain. Week 6 score was calculated as the mean of average daily pain NRS scores over the past 7 days before Week 6 visit. Number of participants with >=30% or >=50% of sustained reduction (defined as reduction that was maintained for a minimum duration of 4 consecutive days) in average daily pain scores from baseline at Week 6 were reported. | Baseline, Week 6 | 
| Number of Participants With at Least 30 Percent (%) and 50% Reduction From Baseline in Average Daily Pain Numeric Rating Scale (NRS) Score at Week 1, 2, 4, 6, 8, 12 and 16 | Participants assessed their average daily pain during the past 24 hours on an 11--point NRS ranging from 0 (no pain) to 10 (worst possible pain) with lower scores indicating less pain. Post-baseline weekly scores were calculated as the mean of average daily pain NRS scores over the past 7 days for each specified time point. Number of participants with >=30% or >=50% of reduction in average daily pain scores from baseline at Week 1, 2, 4, 6, 8, 12 and 16 were reported. | Baseline, Week 1, 2, 4, 6, 8, 12, 16 | 
| Time to Achieve at Least 30% (Percent) and 50% Sustained Reduction From Baseline in Average Daily Pain Score | Time to achieve >=30% or >=50% sustained reduction from baseline (defined as reduction from baseline that was maintained for a total of 4 consecutive days) in average daily pain score was summarized using the Kaplan-Meier estimates. Participants assessed their average daily pain during the past 24 hours on an 11-point NRS ranging from 0 (no pain) to 10 (worst possible pain) with lower scores indicating less pain. | Baseline up to Week 16 | 
| Total Duration of at Least 30 Percent (%) and 50% Reduction From Baseline in Average Daily Pain Numeric Rating Scale (NRS) Score in Participants | Total duration of response was defined as total number of days with a reduction of >=30% or >=50% in average daily pain score from baseline to Week 16. Participants assessed their average daily pain during the past 24 hours on an 11-point NRS ranging from 0 (no pain) to 10 (worst possible pain) with lower scores indicating less pain. Total duration with at least of >=30% or >=50% percent reduction in average daily pain NRS scores from Baseline to Week 16 were reported. | Baseline to Week 16 | 
| Change From Baseline in Modified Brief Pain Inventory- Short Form (mBPI-sf) Score for Pain Interference With CS Score, GA Subtest and NW Subtest at Weeks 1, 2, 4, 6, 8, 12 and 16 | mBPI-sf:questionnaire (5 questions) to assess pain severity and impact of pain on daily functions. Questions 1-4 assess magnitude of pain(Q1 for worst, Q2 for least, Q3 for average and Q4 for pain right now) on an 11-point NRS ranging from 0 (no pain) to 10 (worst possible pain) with lower scores indicate less pain. Question 5 consists 7 item subsets which assess level of interference of pain on daily functions: 1: general activity (GA),2: mood, 3: walking ability, 4: normal work (NW),5: relations with other,6: sleep, 7: enjoyment of life. Each item assessed on an 11-point NRS ranging from 0 (no interference) to 10 (complete interference), where lower scores =less interference of pain. These 7 items were averaged to obtain pain interference composite score (CS), ranging from 0 (no interference) to 10 (complete interference), where lower scores =less interference of pain. Change from baseline in mBPI-sf score for pain interference with CS score, GA subtest and NW subtest were reported. | Baseline, Week 1, 2, 4, 6, 8, 12 and 16 | 
| Number of Participants With Change From Baseline in Patient's Global Assessment of Pain Score at Weeks 1, 2, 4, 6, 8, 12 and 16 | Patient's global assessment of pain from post-herpetic neuralgia assessed participant's overall impression of disease activity. Participants answered: Considering all the ways your pain from post-herpetic neuralgia, 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) with lower scores indicating better condition. Number of participants who reported a change from Baseline of -4, -3, -2, -1, 0, 1, 2, 3, 4 in Patient's Global Assessment of Pain scores at each specified time-point were presented. | Baseline, Week 1, 2, 4, 6, 8 ,12, 16 | 
| Number of Participants With Each Response Level of Patient's Global Evaluation of Study Medication | Participants provided their response for patient's global evaluation of study medication by answering a question. 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 indicating better overall response to the treatment. Number of participants with each response level (poor, fair, good and excellent) were reported. | Week 1, 2, 4, 6, 8, 12, 16 | 
| Change From Baseline in Modified Brief Pain Inventory-Short Form (mBPI-sf) Score for Pain Interference With Sleep at Weeks 1, 2, 4, 6, 8 ,12 and 16 | mBPI-sf is a self-administered questionnaire (5 questions) to assess pain severity and impact of pain on daily functions. Questions (Q) 1-4 assess magnitude of pain severity (Q1 for worst, Q2 for least, Q3 for average, Q4 for pain right now) on an 11-point NRS ranging from 0 (no pain) to 10 (worst possible pain) with lower scores indicate less pain. Question 5 consists of 7 item subsets which assess the level of interference of pain on daily functions: 1: general activity, 2: mood, 3: walking ability, 4: normal work, 5: relations with other, 6: sleep, 7: enjoyment of life. Each item was assessed on an 11-point NRS ranging from 0 (no interference) to 10 (complete interference), where lower scores indicated less interference of pain. Change from Baseline in mBPI-sf score for pain interference with sleep were reported. | Baseline, Week 1, 2, 4, 6, 8, 12, 16 | 
| Number of Participants Who Discontinued the Study Due to Lack of Efficacy |  | Baseline up to Week 16 | 
| Time to Discontinuation Due to Lack of Efficacy | Time to discontinuation due to lack of efficacy was defined as the time interval from the date of study drug administration up to the date of discontinuation of participant from study due to lack of efficacy. | Baseline up to Week 16 | 
| Number of Participants Who Used Rescue Medications | In case of inadequate pain relief for post-herpetic neuralgia, acetaminophen up to 3000 mg per day up to 3 days in a week could be taken as rescue medication. Number of participants with any use of rescue medication during the specified study week were summarized. | Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 | 
| Duration of Rescue Medication Use | In case of inadequate pain relief for post-herpetic neuralgia, acetaminophen up to 3000 mg per day up to 3 days in a week could be taken as rescue medication. Number of days participant used rescue medication, during the specified weeks were summarized. | Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 | 
| Amount of Rescue Medication Taken | In case of inadequate pain relief for post-herpetic neuralgia, acetaminophen up to 3000 mg per day up to 3 days in a week could be taken as rescue medication. The total dosage of acetaminophen (in mg) used during the specified week were summarized. | Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 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 (immediate risk of dying); 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 (up to Week 16) that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious adverse events. | Baseline up to 112 days after the last dose of study drug (up to Week 16) | 
| Number of Participants With Abnormal Physical Examinations Findings at Screening | Physical examination included the examination of abdomen, ears, extremities, eyes, general appearance, head, heart, lungs, musculoskeletal assessment, neck, nose, skin, throat and thyroid. Abnormalities in physical examination was based on investigator's discretion. | Screening visit (1 day prior to Day 1 baseline visit) | 
| Number of Participants With Change From Baseline in Physical Examinations Findings at Week 16 | Physical examination included the examination of abdomen, ears, extremities, eyes, general appearance, head, heart, lungs, musculoskeletal assessment, neck, nose, skin, throat and thyroid. | Baseline, Week 16 | 
| Number of Participants With Change From Baseline in Neurological Examination Findings at Week 16 | Neurological examination included the assessment of cranial nerve function, coordination, reflexes, proprioception, mental status, motor function, gait and station and sensory function (sharp sensation, warm/cold sensation, light touch, deep pressure, and vibration sensation). | Baseline, Week 16 | 
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs at Week 16 | Vital signs included the assessment of the following: body temperature, blood pressure, heart rate and respiratory rate. Criteria for clinically significant vital signs included: heart rate value of less than (<) 40 beats per minute and greater than (>) 150 beats per minute, systolic blood pressure (SBP) of <80 or >210 millimeter of mercury (mmHg), diastolic blood pressure (DBP) of <40 or >130 mmHg, body temperature <32 or >40 degree centigrade, respiratory rate of <10 or >50 breaths/minute. | Baseline, Week 16 | 
| Number of Participants With Laboratory Abnormalities | Abnormality criteria: hematology (hemoglobin; hematocrit; red blood cell count [less than {<}0.8* lower limit of normal [LLN], platelets <0.5* LLN,>1.75* upper limit of normal (ULN), white blood cell count<0.6* LLN, >1.5* ULN, liver function (total bilirubin>1.5* ULN, aspartate aminotransferase; alanine aminotransferase; gamma GT, LDH, alkaline phosphatase>3.0* ULN, total protein; albumin<0.8* LLN; >1.2* ULN), renal function (blood urea nitrogen; creatinine>1.3* ULN, uric acid>1.2* ULN), lipids (cholesterol, triglycerides >1.3*ULN), electrolytes (sodium <0.95* LLN, >1.05* ULN; potassium; chloride; calcium; magnesium; phosphate; bicarbonate<0.9* LLN, >1.1* ULN), chemistry (glucose <0.6*LLN, >1.5*ULN; creatine kinase >2.0*ULN), urinalysis (specific gravity <1.003, >1.030; pH<4.5, >8, glucose; protein; blood; ketones; urobilinogen; bilirubin; nitrite, esterase>=1). | Baseline up to Week 16 | 
| Number of Participants With Electrocardiogram (ECG) Abnormalities | Criteria for abnormality in ECG parameters: Maximum corrected QT interval (QTc) in range of 450 to less than 480 millisecond (msec), Maximum QTcB interval (Bazett's Correction) (msec) in range of 450 to less than 480 msec, Maximum QTcF interval (Fridericia's Correction) in range of 450 to less than 480 msec, maximum QTc interval increase from baseline in range of 30 to less than 60 msec and >=60 msec. | Baseline up to Week 16 | 
| Number of Participants With Positive Anti-Drug Antibody (ADA) Response | Human serum ADA samples were analyzed for the presence or absence of anti--tanezumab antibodies by using a semi quantitative enzyme -linked immunosorbent assay (ELISA). Participants tested positive for ADA response on at least one post-baseline visit were reported. Participants with ADA titer level >=4.32 for PF-04383119 were considered as ADA positive. | Baseline up to Week 16 | 
| Change From Baseline in Hopkins Verbal Learning Test - Revised (HVLT-R) at Week 2, 6, 12, 16 and End of Study | HVLT-R was a word-list learning and memory test used to assess the changes in memory. The task was repeated, for a total of 3 learning trials. After a delay interval of 20 to 25 minutes, delayed recall trial was administered. 1)Learning efficiency: Assessed by examining the learning curve over 3 learning trials and by evaluating the sum of the scores for all 3 learning trials. Raw scores for each of the 3 learning trials were summed for the total recall (TR) score. The TR score ranges from 0 to 36, where higher scores indicated greater verbal learning and recall, 2) Ability to access newly learned information: Assessed by the number of words retained on the delayed recall (DR) trial and the percentage of words recalled from the word list. DR trial score ranges from 0 to 12, where higher scores indicated greater verbal learning and recall. | Baseline, Week 2, 6, 12, 16, end of study (i.e. anytime up to Week 16) | 
| Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) for Tanezumab | AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). | Predose (0 hour) and 1, 2, 192, 193, 672, 673, 1008, 1009, 2016, 2017 and 2688 hours post dose on Day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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monoclonal antibody