NP2 Enkephalin For Treatment of Intractable Cancer Pain

Study Overview
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Brief Summary
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The purpose of this study is to examine the impact of intradermal delivery of NP2 on pain scores and pain medication usage in subjects with intractable pain due to malignant disease. A second purpose is to confirm safety and secondary efficacy measurements.

Detailed Description
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Chronic severe pain remains a significant unmet medical need in patients that have progressive cancer. Existing treatments have limited efficacy and also suffer significant side effects. This is a multi-center, randomized, double blind, placebo-controlled clinical trial designed to evaluate the impact of intradermal injection of NP2 in subjects who have intractable pain due to malignant disease. NP2 is a gene transfer vector engineered to express human preproenkephalin, a gene naturally involved in pain control. Delivery of NP2 directly to the site of pain caused by cancer is intended to provide increased Enkephalin peptides, which bind to opioid receptors, that may allow better pain control.

Official Title
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A Phase II, Randomized, Double Blind, Placebo-controlled, Multicenter Study to Investigate the Impact of NP2 in Subjects With Intractable Pain Due to Malignancy

Conditions
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Intractable Pain, Neoplasms

Intervention / Treatment
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* Biological: NP2
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Histologically confirmed malignant disease. Intractable pain related to malignancy. Females must be postmenopausal or practicing birth control. Able to provide appropriate written consent. Main Exclusion Criteria: Positive pregnancy test prior to receiving study treatment. Serious uncontrolled medical condition other than malignancy (e.g. congestive heart failure, coagulopathy, uncontrolled diabetes). Evidence of active Hepatitis B, Hepatitis C, or HIV infection. Evidence of viral, bacterial, or fungal infection in the planned treatment area.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active NP2<br>Single intradermal dose of active NP2. An open label study extension will offer up to two additional doses of active NP2 between weeks 4-10 following the previous dose. | Biological: NP2<br>* NP2 is a replication defective HSV-1 based gene transfer vector engineered to express human preproenkephalin. The drug will be injected intradermally corresponding to the distribution of the malignancy-related pain. The total amount to be injected will be a dose volume of 1.0 ml delivered in a single session on Study Day 0.<br>|
| Placebo Comparator: Placebo<br>Single intradermal dose of placebo (vehicle). An open label study extension will offer up to two additional doses of active NP2 between weeks 4-10 following the previous dose. | Biological: Placebo<br>* The placebo (vehicle) will be injected intradermally corresponding to the distribution of the malignancy-related pain. The total amount to be injected will be a dose volume of 1.0 ml delivered in a single session on Study Day 0.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Measured by the Numerical Rating Scale (NRS) | • Change from baseline of the average daily NRS pain score (scale of 0 to 10 ) of Placebo compared to Active NP2 cohorts. | Days -5 to -1 predosing and days 3 to 14 postdosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Opioid Pain Medication Usage Morphine Equivalent Units (MEU) | •Change from baseline of use of opioid pain medication average daily MEU of Placebo compared to Active NP2 cohorts | Days -5 to -1 predosing and 3 to 14 postdosing | 
| Quality of Life ECOG | •Quality of Life measured by Eastern Cooperative Oncology Group Performance Status (ECOG) assessment at follow-up visits compared to baseline of Placebo compared to Active NP2 cohorts. | Baseline and Week 1, 2 and 4 | 
| Quality of Life SF-12 | •Quality of Life measured by the 12-Item Short Form Health Survey (SF-12v2) at follow-up visits compared to baseline of Placebo compared to Active NP2 cohorts. | Baseline and Week 1, 2 and 4 | 
| Pain SF-MPQ | •Short Form McGill Pain Questionnaire (SF-MPQ-2) assessment at follow-up visits compared to baseline of Placebo compared to Active NP2 cohorts | Baseline and Week 1, 2 and 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pain, cancer, malignancy, intractable, gene therapy, enkephalin, opioid