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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Subjects who received Engensis (VM202) | Experimental | VM202, Engensis |
|
| Subjects who received Placebo | Placebo Comparator | Placebo, vehicle |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Long-Term Follow-Up of Patients who Received Engensis (VM202) | Genetic | 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. |
| 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 and Treatment-emergent Serious Adverse Events for Subjects who received Engensis or Placebo (in the prior VMDN-003 study) | Baseline through Day 365 |
| 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). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| John A. Kessler, MD | Northwestern University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Arizona Research Center | Phoenix | Arizona | 85023 | United States | ||
| Clinical Trials, Inc. |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 |
| Title | Milestones | Reasons Not Completed | ||||
|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jul 30, 2019 | Sep 28, 2022 |
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Long term, prospective, non-interventional, safety extension study of phase 3 trial. Double blind, randomized, placebo-controlled, multicenter study
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Double-blind
|
| Long-Term Follow-Up of Patients who Received Placebo | Drug | 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. |
|
| 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 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. | 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 |
| Little Rock |
| Arkansas |
| 72205 |
| United States |
| Northern California Research | Sacramento | California | 95821 | United States |
| Center for Clinical Research | San Francisco | California | 94115 | United States |
| Neurological Research Institute | Santa Monica | California | 90404 | United States |
| Diablo Clinical Research, Inc. | Walnut Creek | California | 94598 | United States |
| Innovative Research of West Florida | Clearwater | Florida | 33756 | United States |
| University of Florida McKnight Brain Institute | Gainesville | Florida | 32611 | United States |
| Clinical Research of West Florida | Tampa | Florida | 33603 | United States |
| The Brigham and Women's Hospital | Boston | Massachusetts | 02115 | United States |
| Raleigh Neurology Associates, P.A. | Raleigh | North Carolina | 27607 | United States |
| Nerve and Muscle Center of Texas | Houston | Texas | 77030 | United States |
| EVMS (Eastern Virginia Medical School) | Norfolk | Virginia | 23510 | United States |
| Rainier Clinical Research Center, Inc. | Renton | Washington | 98057 | United States |
| 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. |
|
| COMPLETED |
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| NOT COMPLETED |
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The safety population included all participants who signed consent for the safety extension study. Participants in the safety analysis population were analyzed according to the treatment received in the VMDN-003 study, regardless of the treatment assigned at randomization.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | 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. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Region of Enrollment | Number | participants |
| ||||||||||||||||||
| Gabapentin and/or Pregabalin Use | Count of Participants | Participants |
| ||||||||||||||||||
| Diabetes Type | The race for one subject who screen failed was missing | Count of Participants | Participants |
| |||||||||||||||||
| Body Mass Index | Mean | Standard Deviation | kg/m^2 |
| |||||||||||||||||
| HbA1c | Mean | Standard Deviation | percent of glycosylated hemoglobin |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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) | Safety population | Posted | Count of Participants | Participants | Baseline through Day 365 |
|
|
| ||||||||||||||||||||||||||||||||||||
| 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). | ITT population | Posted | Mean | Standard Deviation | score on a scale | Baseline to the Day 365 |
| |||||||||||||||||||||||||||||||||||||
| 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). | Intent-to-Treat population | Posted | Mean | Standard Deviation | score on a scale | Day 270 to Day 365 |
|
| ||||||||||||||||||||||||||||||||||||
| 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. | Intent-to-Treat population | Posted | Count of Participants | Participants | At the Day 365 visit |
| ||||||||||||||||||||||||||||||||||||||
| 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). | Intent-to-Treat population subgroup analysis of Subjects without gabapentin and/or pregabalin use | Posted | Least Squares Mean | Standard Error | score on a scale | Baseline to Day 365 |
|
Adverse event data were collected from Day 270 (start of VMDN-003b study) to Day 365
Treatment-emergent adverse events
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. | 0 | 65 | 1 | 65 | 10 | 65 |
| EG001 | 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. | 0 | 36 | 2 | 36 | 8 | 36 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| acute left ventricular failure | Cardiac disorders | MedDRA 21.0 | Non-systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA 21.0 | Non-systematic Assessment |
| |
| Chest pain | General disorders | MedDRA 21.0 | Non-systematic Assessment |
| |
| Transient ischaemic attack | Nervous system disorders | MedDRA 21.0 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute sinusitis | Infections and infestations | MedDRA 21.0 | Non-systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA 21.0 | Non-systematic Assessment |
| |
| Diverticulitis | Infections and infestations | MedDRA 21.0 | Non-systematic Assessment |
| |
| Helicobacter infection | Infections and infestations | MedDRA 21.0 | Non-systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 21.0 | Non-systematic Assessment |
| |
| Viral infection | Infections and infestations | MedDRA 21.0 | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Non-systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Non-systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Non-systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Non-systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Non-systematic Assessment |
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| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Non-systematic Assessment |
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| Osteonecrosis | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Non-systematic Assessment |
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| Angina pectoris | Cardiac disorders | MedDRA 21.0 | Non-systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | MedDRA 21.0 | Non-systematic Assessment |
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| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 21.0 | Non-systematic Assessment |
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| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 21.0 | Non-systematic Assessment |
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| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 21.0 | Non-systematic Assessment |
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| Amnesia | Nervous system disorders | MedDRA 21.0 | Non-systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 21.0 | Non-systematic Assessment |
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| Nerve compression | Nervous system disorders | MedDRA 21.0 | Non-systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Non-systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Non-systematic Assessment |
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| Sleep apnoea syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Non-systematic Assessment |
| |
| Anal skin tags | Gastrointestinal disorders | MedDRA 21.0 | Non-systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 21.0 | Non-systematic Assessment |
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| Haemorrhoids | Gastrointestinal disorders | MedDRA 21.0 | Non-systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 21.0 | Non-systematic Assessment |
| |
| Ankle fracture | Injury, poisoning and procedural complications | MedDRA 21.0 | Non-systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | MedDRA 21.0 | Non-systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | MedDRA 21.0 | Non-systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 21.0 | Non-systematic Assessment |
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| Hypotension | Vascular disorders | MedDRA 21.0 | Non-systematic Assessment |
|
Investigator Agreement
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jinsub Lee, PhD. | Helixmith Co., Ltd. | +82-10-8256-0439 | jinsub.lee@helixmith.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 7, 2019 | Sep 28, 2022 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D003929 | Diabetic Neuropathies |
| D010146 | Pain |
| ID | Term |
|---|---|
| D010523 | Peripheral Nervous System Diseases |
| D009468 | Neuromuscular Diseases |
| D009422 | Nervous System Diseases |
| D048909 | Diabetes Complications |
| D003920 | Diabetes Mellitus |
| D004700 | Endocrine System Diseases |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| >=65 years |
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| Male |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| Type II diabetes |
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| Not reported |
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