Diabetic Neuropathy, Painful, Painful Diabetic Neuropathy
Conditions
Keywords
diabetic, neuropathy, shooting pain, burning pain, pins and needles pain, foot pain, ViroMed, Helixmith, Engensis, VM202
Brief summary
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
In the phase III VMDN-003 study, subjects received 2 treatments of either Engensis (VM202) or placebo administered as intramuscular 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 Hepatocyte Growth Factor make long-term follow-up important both for safety and efficacy: in order for Engensis to be a candidate for chronic treatment of Painful Diabetic Peripheral Neuropathy, 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.
Interventions
GENETICLong-Term Follow-Up of Patients who Received Engensis (VM202)
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.
DRUGLong-Term Follow-Up of Patients who Received Placebo
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.
Sponsors
Helixmith Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blind
Intervention model description
Long term, prospective, non-interventional, safety extension study of phase 3 trial. Double blind, randomized, placebo-controlled, multicenter study
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Were randomized and dosed in the VMDN-003 study 2. Received all intramuscular injections of study drug on Days 0, 14, 90, and 104 in the VMDN-003 study 3. 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
1. Were using an investigational drug or treatment 2. Were unable or unwilling to give informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Long-term Safety for Engensis Versus Placebo | Baseline through Day 365 | Long-term (6 months) safety in terms of the incidence of Treatment-emergent Adverse Events and Treatment-emergent Serious Adverse Events for Subjects who received Engensis or Placebo (in the prior VMDN-003 study) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Change in the Average 24-hour Pain Score From Baseline (Day 0 of Study VMDN-003) to Day 365 for Engensis Versus Placebo | Baseline to the Day 365 | 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). |
| Change in the Average 24-hour Pain Score From Day 270 to Day 365 for Engensis Versus Placebo | Day 270 to Day 365 | 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). |
| Patient's Global Impression of Change at the Day 365 Visit for Engensis Versus Placebo | At the Day 365 visit | The Patient's Global Impression of Change 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 Patient's Global Impression of Change 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 Patient's Global Impression of Change 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. |
| 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 | Baseline to Day 365 | 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). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Subjects Who Received Engensis (VM202) VM202- Engensis
Long-Term Follow-Up of Patients who Received Engensis (VM202): No study drug is administered in this study.
Patients who received Engensis (VM202) in a previous trial will be evaluated in this trial for long-term safety and efficacy. | 65 |
| Subjects Who Received Placebo Placebo, vehicle
Long-Term Follow-Up of Patients who Received Placebo: No study drug is administered in this study.
Patients who received Placebo in a previous trial will be evaluated in this trial for long-term safety and efficacy. | 36 |
| Total | 101 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | screen failure | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Subjects Who Received Engensis (VM202) | Subjects Who Received Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 33 Participants | 16 Participants | 49 Participants |
| Age, Categorical Between 18 and 65 years | 32 Participants | 20 Participants | 52 Participants |
| Age, Continuous | 61.6 years STANDARD_DEVIATION 8.87 | 61.4 years STANDARD_DEVIATION 8.98 | 61.5 years STANDARD_DEVIATION 8.86 |
| Body Mass Index | 32.7 kg/m^2 STANDARD_DEVIATION 4.79 | 33.2 kg/m^2 STANDARD_DEVIATION 5.45 | 32.9 kg/m^2 STANDARD_DEVIATION 5.01 |
| Diabetes Type Not reported | 1 Participants | 0 Participants | 1 Participants |
| Diabetes Type Type I diabetes | 2 Participants | 2 Participants | 4 Participants |
| Diabetes Type Type II diabetes | 62 Participants | 34 Participants | 96 Participants |
| Gabapentin and/or Pregabalin Use | 31 Participants | 17 Participants | 48 Participants |
| HbA1c | 7.37 percent of glycosylated hemoglobin STANDARD_DEVIATION 1.19 | 7.22 percent of glycosylated hemoglobin STANDARD_DEVIATION 0.95 | 7.31 percent of glycosylated hemoglobin STANDARD_DEVIATION 1.11 |
| Race (NIH/OMB) Race American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Race Asian | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Race Black or African American | 9 Participants | 5 Participants | 14 Participants |
| Race (NIH/OMB) Race More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Race Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Race Unknown or Not Reported | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Race White | 53 Participants | 28 Participants | 81 Participants |
| Region of Enrollment United States | 65 participants | 36 participants | 101 participants |
| Sex: Female, Male Female | 25 Participants | 8 Participants | 33 Participants |
| Sex: Female, Male Male | 40 Participants | 28 Participants | 68 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 65 | 0 / 36 |
| other Total, other adverse events | 10 / 65 | 8 / 36 |
| serious Total, serious adverse events | 1 / 65 | 2 / 36 |
Outcome results
Primary
Long-term Safety for Engensis Versus Placebo
Long-term (6 months) safety in terms of the incidence of Treatment-emergent Adverse Events and Treatment-emergent Serious Adverse Events for Subjects who received Engensis or Placebo (in the prior VMDN-003 study)
Time frame: Baseline through Day 365
Population: Safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Subjects Who Received Engensis (VM202) | Long-term Safety for Engensis Versus Placebo | Subjects with at least one Treatment-emergent Adverse Event (TEAE) | 10 Participants |
| Subjects Who Received Engensis (VM202) | Long-term Safety for Engensis Versus Placebo | Subjects with at least one Treatment-emergent Serious Adverse Event (TESAE) | 1 Participants |
| Subjects Who Received Placebo | Long-term Safety for Engensis Versus Placebo | Subjects with at least one Treatment-emergent Adverse Event (TEAE) | 8 Participants |
| Subjects Who Received Placebo | Long-term Safety for Engensis Versus Placebo | Subjects with at least one Treatment-emergent Serious Adverse Event (TESAE) | 2 Participants |
Secondary
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).
Time frame: Day 270 to Day 365
Population: Intent-to-Treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Subjects Who Received Engensis (VM202) | Change in the Average 24-hour Pain Score From Day 270 to Day 365 for Engensis Versus Placebo | 0.26 score on a scale | Standard Deviation 1.525 |
| Subjects Who Received Placebo | Change in the Average 24-hour Pain Score From Day 270 to Day 365 for Engensis Versus Placebo | 0.29 score on a scale | Standard Deviation 1.43 |
Secondary
Patient's Global Impression of Change at the Day 365 Visit for Engensis Versus Placebo
The Patient's Global Impression of Change 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 Patient's Global Impression of Change 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 Patient's Global Impression of Change 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.
Time frame: At the Day 365 visit
Population: Intent-to-Treat population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Subjects Who Received Engensis (VM202) | Patient's Global Impression of Change at the Day 365 Visit for Engensis Versus Placebo | -1: Much worse or very much worse | 1 Participants |
| Subjects Who Received Engensis (VM202) | Patient's Global Impression of Change at the Day 365 Visit for Engensis Versus Placebo | 0: Minimally improved/worsened or no change | 31 Participants |
| Subjects Who Received Engensis (VM202) | Patient's Global Impression of Change at the Day 365 Visit for Engensis Versus Placebo | Not Reported | 2 Participants |
| Subjects Who Received Engensis (VM202) | Patient's Global Impression of Change at the Day 365 Visit for Engensis Versus Placebo | 1: Very much improved or much improved | 31 Participants |
| Subjects Who Received Placebo | Patient's Global Impression of Change at the Day 365 Visit for Engensis Versus Placebo | Not Reported | 0 Participants |
| Subjects Who Received Placebo | Patient's Global Impression of Change at the Day 365 Visit for Engensis Versus Placebo | -1: Much worse or very much worse | 2 Participants |
| Subjects Who Received Placebo | Patient's Global Impression of Change at the Day 365 Visit for Engensis Versus Placebo | 1: Very much improved or much improved | 14 Participants |
| Subjects Who Received Placebo | Patient's Global Impression of Change at the Day 365 Visit for Engensis Versus Placebo | 0: Minimally improved/worsened or no change | 20 Participants |
p-value: 0.219Cochran-Mantel-Haenszel
Secondary
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).
Time frame: Baseline to Day 365
Population: Intent-to-Treat population subgroup analysis of Subjects without gabapentin and/or pregabalin use
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Subjects Who Received Engensis (VM202) | 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 | -2.30 score on a scale | Standard Error 0.352 |
| Subjects Who Received Placebo | 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 | -0.82 score on a scale | Standard Error 0.47 |
p-value: 0.015595% CI: [-2.67, -0.29]Mixed Models Analysis
Secondary
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).
Time frame: Baseline to the Day 365
Population: ITT population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Subjects Who Received Engensis (VM202) | The Change in the Average 24-hour Pain Score From Baseline (Day 0 of Study VMDN-003) to Day 365 for Engensis Versus Placebo | -2.32 score on a scale | Standard Deviation 2.36 |
| Subjects Who Received Placebo | The Change in the Average 24-hour Pain Score From Baseline (Day 0 of Study VMDN-003) to Day 365 for Engensis Versus Placebo | -1.49 score on a scale | Standard Deviation 1.76 |
p-value: 0.04695% CI: [-1.76, -0.02]Mixed Models Analysis