Diabetic Peripheral Neuropathy
Conditions
Brief summary
To evaluate the durability of efficacy and long-term safety of intramuscular administration of Engensis or Placebo that was administered in the double-blind, randomized, VMDN-003-2 Placebo-controlled Phase 3 Study.
Detailed description
The purpose of this 6-month extension study (VMDN-003-2b) is to evaluate the durability of efficacy and long-term safety of intramuscular administration of Engensis or Placebo that was administered in the double-blind, randomized, VMDN-003-2 Placebo-controlled Phase 3 Study. No treatments will be administered in this VMDN-003-2b extension study. The combined overall duration of the VMDN-003-2 and VMDN-003-2b studies will be 12 months. Participants will be enrolled in the VMDN-003-2b study at completion of the Day 180 Visit of Study VMDN-003-2. Participants will continue to be identified by the same Participant number and the same treatment group (Engensis or Placebo) assigned by randomization in Study VMDN-003-2. No study drug or treatment will be administered in this VMDN-003-2b extension study. The double-blind treatment assignment from the prior study will be maintained for Investigators and Participants during this extension study. This extension study will assess the durability of efficacy and long-term safety of Engensis compared to Placebo as measured by changes in Average Daily Pain Score of the full Brief Pain Inventory for Diabetic Peripheral Neuropathy, Bedside sensory testing, physical examinations, laboratory assessments, vital signs, treatment-emergent adverse events, treatment-emergent serious adverse events, and adverse events of special interest.
Interventions
BIOLOGICALEngensis
Injections with Engensis in study VMDN-003-2
OTHERPlacebo
Injections with Placebo in study VMDN-003-2
Sponsors
Helixmith Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Completed study VMDN-003-2 and consent to enroll in study VMDN-003-2b
Exclusion criteria
* None
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To Evaluate the Efficacy of Intramuscular Administration of Engensis on Reducing Pain in Participants With Painful Diabetic Peripheral Neuropathy in the Feet and Lower Legs as Compared to Placebo | From the 7 days prior to the Day 0 Visit (Study VMDN-003-2, NCT04469270), Day 270, to the 7 days prior to the Day 365 Visit in the intent-to-treat population | Change in the means of the Average Daily Pain Scores from the full Brief Pain Inventory for Diabetic Peripheral Neuropathy from the 7 days prior to the Day 0 Visit (Study VMDN-003-2) to the 7 days prior to the Day 365 Visit in the intent-to-treat population. The mean of the Average Daily Pain Scores are used for the primary endpoint recorded in the 7 days prior to the Days 270 and 365/ET Visits. The Brief Pain Inventory for Diabetic Peripheral Neuropathy scale is a 0 to 10 point scale with 10 being Pain as bad as you can imagine. The mean of at least 5 daily pain scores recorded for Question 5 of the Brief Pain Inventory for Diabetic Peripheral Neuropathy scale in electronic diary during the 7 days prior to the visits on Days 270 and 365/Early termination. The greater the negative difference between the followup visit and the Day 0 Baseline for each group for the average daily pain score in participants, would indicate that the average daily pain is declining. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Evaluate the Efficacy of IM Administration of Engensis on the Worst Pain in Participants With Painful Diabetic Peripheral Neuropathy in the Feet and Lower Legs as Compared to Placebo | From the 7 days prior to the Day 0 Visit (Study VMDN-003-2) to the 7 days prior to the Day 365 Visit for Engensis compared to Placebo | Change in the means of the Worst Pain Scores from the full Brief Pain Inventory for Diabetic Peripheral Neuropathy from the 7 days prior to Day 0 Visit (Study VMDN-003-2), to Day 270, and 7 days prior to the Day 365 Visit for Engensis compared to Placebo. The Brief Pain Inventory for Diabetic Peripheral Neuropathy scale is a 0 to 10 point scale with 10 being Pain as bad as you can imagine. The mean of at least 5 worst daily pain scores recorded for Question 3 of the Brief Pain Inventory for Diabetic Peripheral Neuropathy in the electronic diary during the 7 days prior to the Visits on Days 270 and 365/Early termination. The greater the negative difference between the followup visit and the Day 0 Baseline for each group for the worst pain score in participants, would indicate that the worst pain is declining. |
| To Evaluate the Safety of IM Administration of Engensis in the Number of Participants With Painful DPN in the Feet and Lower Legs as Compared to Placebo | From Day 0 Visit (Study VMDN-003-2) to the Day 365 Visit | Number of participants with adverse events and serious adverse events for Engensis compared to Placebo, including the number of participants with clinically significant laboratory values for Engensis compared to Placebo |
| To Evaluate the Efficacy of Administration of Engensis on Reducing Pain in Participants With Painful Diabetic Peripheral Neuropathy in the Feet and Lower Legs | From the 7 days prior to the Day 0 Visit (Study VMDN-003-2), to the 7 days prior to the Day 270 Visit, and 7 days prior to the Day 365 Visit | Proportion of Responders (≥ 50% reduction in the Average Daily Pain Scores from the full Brief Pain Inventory for Diabetic Peripheral Neuropathy) from the 7 days prior to the Day 0 Visit (Study VMDN-003-2) to the 7 days prior to the Day 270 Visit and the 7 days prior to the Day 365 Visit for Engensis compared to Placebo. |
Countries
United States
Participant flow
Recruitment details
Qualified subjects were anyone that completed the Day 180 visit in VMDN-003-2 (NCT04469270) and provided informed consent to be followed for another 6 months in this extension protocol VMDN-003-2b (NCT04873232). Subjects did not receive any further investigational prouct interventions.
Participants by arm
| Arm | Count |
|---|---|
| Engensis Patients who have received Engensis in protocol VMDN-003-2
Engensis: Injections with Engensis in study VMDN-003-2 | 49 |
| Placebo Patients who have received Placebo in protocol VMDN-003-2
Placebo: Injections with Placebo in study VMDN-003-2 | 57 |
| Total | 106 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 4 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Engensis | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 20 Participants | 23 Participants | 43 Participants |
| Age, Categorical Between 18 and 65 years | 29 Participants | 34 Participants | 63 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 8 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 42 Participants | 49 Participants | 91 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 17 Participants | 26 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 37 Participants | 36 Participants | 73 Participants |
| Sex: Female, Male Female | 18 Participants | 14 Participants | 32 Participants |
| Sex: Female, Male Male | 31 Participants | 43 Participants | 74 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 49 | 0 / 57 |
| other Total, other adverse events | 16 / 49 | 22 / 57 |
| serious Total, serious adverse events | 3 / 49 | 6 / 57 |
Outcome results
Primary
To Evaluate the Efficacy of Intramuscular Administration of Engensis on Reducing Pain in Participants With Painful Diabetic Peripheral Neuropathy in the Feet and Lower Legs as Compared to Placebo
Change in the means of the Average Daily Pain Scores from the full Brief Pain Inventory for Diabetic Peripheral Neuropathy from the 7 days prior to the Day 0 Visit (Study VMDN-003-2) to the 7 days prior to the Day 365 Visit in the intent-to-treat population. The mean of the Average Daily Pain Scores are used for the primary endpoint recorded in the 7 days prior to the Days 270 and 365/ET Visits. The Brief Pain Inventory for Diabetic Peripheral Neuropathy scale is a 0 to 10 point scale with 10 being Pain as bad as you can imagine. The mean of at least 5 daily pain scores recorded for Question 5 of the Brief Pain Inventory for Diabetic Peripheral Neuropathy scale in electronic diary during the 7 days prior to the visits on Days 270 and 365/Early termination. The greater the negative difference between the followup visit and the Day 0 Baseline for each group for the average daily pain score in participants, would indicate that the average daily pain is declining.
Time frame: From the 7 days prior to the Day 0 Visit (Study VMDN-003-2, NCT04469270), Day 270, to the 7 days prior to the Day 365 Visit in the intent-to-treat population
Population: Summary of Change from Baseline to Day 365 in ADPS (Intent-To-Treat Population)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Engensis | To Evaluate the Efficacy of Intramuscular Administration of Engensis on Reducing Pain in Participants With Painful Diabetic Peripheral Neuropathy in the Feet and Lower Legs as Compared to Placebo | Change from Baseline to Day 270 | -2.27 score on a scale | Standard Deviation 2.083 |
| Engensis | To Evaluate the Efficacy of Intramuscular Administration of Engensis on Reducing Pain in Participants With Painful Diabetic Peripheral Neuropathy in the Feet and Lower Legs as Compared to Placebo | Change from Baseline to 7 Days prior to the Day 365 visit | -2.53 score on a scale | Standard Deviation 2.173 |
| Placebo | To Evaluate the Efficacy of Intramuscular Administration of Engensis on Reducing Pain in Participants With Painful Diabetic Peripheral Neuropathy in the Feet and Lower Legs as Compared to Placebo | Change from Baseline to Day 270 | -2.62 score on a scale | Standard Deviation 2.087 |
| Placebo | To Evaluate the Efficacy of Intramuscular Administration of Engensis on Reducing Pain in Participants With Painful Diabetic Peripheral Neuropathy in the Feet and Lower Legs as Compared to Placebo | Change from Baseline to 7 Days prior to the Day 365 visit | -2.78 score on a scale | Standard Deviation 2.126 |
Secondary
To Evaluate the Efficacy of Administration of Engensis on Reducing Pain in Participants With Painful Diabetic Peripheral Neuropathy in the Feet and Lower Legs
Proportion of Responders (≥ 50% reduction in the Average Daily Pain Scores from the full Brief Pain Inventory for Diabetic Peripheral Neuropathy) from the 7 days prior to the Day 0 Visit (Study VMDN-003-2) to the 7 days prior to the Day 270 Visit and the 7 days prior to the Day 365 Visit for Engensis compared to Placebo.
Time frame: From the 7 days prior to the Day 0 Visit (Study VMDN-003-2), to the 7 days prior to the Day 270 Visit, and 7 days prior to the Day 365 Visit
Population: Summary of Participant Responders with ≥50% reduction from Baseline Day 0 visit, in the Average Daily Pain Score to the 7 days prior to Day 270 and 7 days prior to the Day 365 visit (Intent-To-Treat Population)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Engensis | To Evaluate the Efficacy of Administration of Engensis on Reducing Pain in Participants With Painful Diabetic Peripheral Neuropathy in the Feet and Lower Legs | Responders with ≥50% reduction by Day 270 | 17 Participants |
| Engensis | To Evaluate the Efficacy of Administration of Engensis on Reducing Pain in Participants With Painful Diabetic Peripheral Neuropathy in the Feet and Lower Legs | Responders with ≥50% reduction by Day 365 | 16 Participants |
| Placebo | To Evaluate the Efficacy of Administration of Engensis on Reducing Pain in Participants With Painful Diabetic Peripheral Neuropathy in the Feet and Lower Legs | Responders with ≥50% reduction by Day 270 | 27 Participants |
| Placebo | To Evaluate the Efficacy of Administration of Engensis on Reducing Pain in Participants With Painful Diabetic Peripheral Neuropathy in the Feet and Lower Legs | Responders with ≥50% reduction by Day 365 | 27 Participants |
Secondary
To Evaluate the Efficacy of IM Administration of Engensis on the Worst Pain in Participants With Painful Diabetic Peripheral Neuropathy in the Feet and Lower Legs as Compared to Placebo
Change in the means of the Worst Pain Scores from the full Brief Pain Inventory for Diabetic Peripheral Neuropathy from the 7 days prior to Day 0 Visit (Study VMDN-003-2), to Day 270, and 7 days prior to the Day 365 Visit for Engensis compared to Placebo. The Brief Pain Inventory for Diabetic Peripheral Neuropathy scale is a 0 to 10 point scale with 10 being Pain as bad as you can imagine. The mean of at least 5 worst daily pain scores recorded for Question 3 of the Brief Pain Inventory for Diabetic Peripheral Neuropathy in the electronic diary during the 7 days prior to the Visits on Days 270 and 365/Early termination. The greater the negative difference between the followup visit and the Day 0 Baseline for each group for the worst pain score in participants, would indicate that the worst pain is declining.
Time frame: From the 7 days prior to the Day 0 Visit (Study VMDN-003-2) to the 7 days prior to the Day 365 Visit for Engensis compared to Placebo
Population: Summary of Change from Day 0, Baseline, to Day 270, and Day 365 in Worst Pain Score (MI) (Intent-To-Treat Population)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Engensis | To Evaluate the Efficacy of IM Administration of Engensis on the Worst Pain in Participants With Painful Diabetic Peripheral Neuropathy in the Feet and Lower Legs as Compared to Placebo | Change from Baseline to Day 270 | -2.50 units on a scale | Standard Deviation 2.376 |
| Engensis | To Evaluate the Efficacy of IM Administration of Engensis on the Worst Pain in Participants With Painful Diabetic Peripheral Neuropathy in the Feet and Lower Legs as Compared to Placebo | Change from Baseline to Day 365 | -2.65 units on a scale | Standard Deviation 2.485 |
| Placebo | To Evaluate the Efficacy of IM Administration of Engensis on the Worst Pain in Participants With Painful Diabetic Peripheral Neuropathy in the Feet and Lower Legs as Compared to Placebo | Change from Baseline to Day 270 | -2.94 units on a scale | Standard Deviation 2.664 |
| Placebo | To Evaluate the Efficacy of IM Administration of Engensis on the Worst Pain in Participants With Painful Diabetic Peripheral Neuropathy in the Feet and Lower Legs as Compared to Placebo | Change from Baseline to Day 365 | -3.19 units on a scale | Standard Deviation 2.454 |
Secondary
To Evaluate the Safety of IM Administration of Engensis in the Number of Participants With Painful DPN in the Feet and Lower Legs as Compared to Placebo
Number of participants with adverse events and serious adverse events for Engensis compared to Placebo, including the number of participants with clinically significant laboratory values for Engensis compared to Placebo
Time frame: From Day 0 Visit (Study VMDN-003-2) to the Day 365 Visit
Population: Overall Summary of number of participants with Adverse Events (Safety Population)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Engensis | To Evaluate the Safety of IM Administration of Engensis in the Number of Participants With Painful DPN in the Feet and Lower Legs as Compared to Placebo | 16 Participants |
| Placebo | To Evaluate the Safety of IM Administration of Engensis in the Number of Participants With Painful DPN in the Feet and Lower Legs as Compared to Placebo | 22 Participants |