Extension of Phase 3 Gene Therapy for Painful Diabetic Neuropathy

Study Overview
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Brief Summary
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The purpose of this study is to explore the overall safety profile and durability of efficacy of Engensis (VM202) in painful diabetic peripheral neuropathy. All subjects still in follow-up for the VMDN-003 study or who have completed the Day 270 visit within the prior 90 days will be approached to enroll in the long-term safety extension study.

Detailed Description
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In the phase III VMDN-003 study, subjects received 2 treatments of either Engensis (VM202) or placebo administered as intramuscular (IM) injections into bilateral calves on Days 0 and 14, and Days 90 and 104. Primary efficacy was evaluated 90 days following the first injection. The growth potential for HGF make long-term follow-up important both for safety and efficacy: in order for Engensis to be a candidate for chronic treatment of PDPN, it must be demonstrated not to induce unexpected adverse events with repeated dosing; and the potential for reversal or stabilization of diabetic neuropathy using only one or two treatments of Engensis may make it especially attractive compared to current treatments which must be taken daily for the duration of the disease. A safety extension to the VMDN-003 study is therefore warranted.

Official Title
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Long-term, Prospective, Non-interventional, Extension of a Phase III, Randomized, Placebo-controlled, Multicenter Study to Assess the Safety & Efficacy of Engensis (VM202) in Subjects With Painful Diabetic Peripheral Neuropathy

Conditions
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Painful Diabetic Neuropathy, Diabetic Neuropathy, Painful

Intervention / Treatment
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* Genetic: Long-Term Follow-Up of Patients who Received Engensis (VM202)
* Drug: Long-Term Follow-Up of Patients who Received Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Were randomized and dosed in the VMDN-003 study Received all IM injections of study drug on Days 0, 14, 90, and 104 in the VMDN-003 study Were in follow-up for the VMDN-003 study or had completed Day 270 within the last 90 days prior to signing consent Exclusion Criteria: Were using an investigational drug or treatment Were unable or unwilling to give informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Interventional Model Description: Long term, prospective, non-interventional, safety extension study of phase 3 trial. Double blind, randomized, placebo-controlled, multicenter study/
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Subjects who received Engensis (VM202)<br>VM202, Engensis | Genetic: Long-Term Follow-Up of Patients who Received Engensis (VM202)<br>* No study drug is administered in this study. Patients who received Engensis (VM202) in the previous trial (VMDN-003) will remain blinded and were evaluated in this trial for long-term safety and efficacy.<br>|
| Placebo Comparator: Subjects who received Placebo<br>Placebo, vehicle | Drug: Long-Term Follow-Up of Patients who Received Placebo<br>* No study drug is administered in this study. Patients who received Placebo in the previous trial (VMDN-003) will remain blinded and were evaluated in this trial for long-term safety and efficacy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Long-term Safety for Engensis Versus Placebo | Long-term (6 months) safety in terms of the incidence of Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) for Subjects who received Engensis or Placebo (in the prior VMDN-003 study) | Baseline through Day 365 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Change in the Average 24-hour Pain Score From Baseline (Day 0 of Study VMDN-003) to Day 365 for Engensis Versus Placebo | The Average 24-hour Pain Score was obtained from the Daily Pain and Sleep Interference Diary. The change in the Average 24-hour Pain Score was determined from baseline (Day 0 of Study VMDN-003) to the Day 365 visit. The Average 24-hour Pain Score is an 11-point numerical scale with scores from 0 (No Pain) to 10 (Worst Possible Pain). | Baseline to the Day 365 | 
| Change in the Average 24-hour Pain Score From Day 270 to Day 365 for Engensis Versus Placebo | The Average 24-hour Pain Score is from the Daily Pain and Sleep Interference Diary. The change in the Average 24-hour Pain Score was determined for Day 270 to Day 365. The Average 24-hour Pain Score is an 11-point numerical scale with scores from 0 (No Pain) to 10 (Worst Possible Pain). | Day 270 to Day 365 | 
| Patient's Global Impression of Change (PGIC) at the Day 365 Visit for Engensis Versus Placebo | The Patient's Global Impression of Change (PGIC) was completed by subjects (self-administered) at the Day 365 visit. The subject evaluated how his/her overall status had changed since the start of the study using a 7-point PGIC questionnaire scale, where 1 = Very Much Improved, 2 = Much Improved, 3 = Minimally Improved, 4 = No Change, 5 = Minimally Worse, 6 = Much Worse, and 7 = Very Much Worse. The Outcome Measure was the PGIC Categories of Scores as follows: 1 = Very Much Improved or Much Improved, 0 = Minimally Improved/Worsened or No Change, and -1 = Much Worse or Very Much Worse. | At the Day 365 visit | 
| Subgroup Analysis of the Change in the Average 24-hour Pain Score From Baseline (Day 0 of Study VMDN-003) to Day 365 for Engensis Versus Placebo for Subjects Without Gabapentin and/or Pregabalin Use at Baseline | The Average 24-hour Pain Score was obtained from the Daily Pain and Sleep Interference Diary and the change in the Average 24-hour Pain Score from baseline (Day 0 of Study VMDN-003) to the Day 365 follow-up was determined. The Average 24-hour Pain Score is an 11-point numerical scale with scores from 0 (No Pain) to 10 (Worst Possible Pain). | Baseline to Day 365 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetic, neuropathy, shooting pain, burning pain, pins and needles pain, foot pain, ViroMed, Helixmith, Engensis, VM202