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The purpose of this study is to evaluate whether intramuscular injections of VM202 into the calf is safe and effective in the treatment of critical limb ischemia.
In the absence of revascularization options, most patients with CLI require amputation within 6 months. Patients requiring major amputation face a diminished quality of life, an unfavorable natural history and need extensive resources for their post-amputation rehabilitation and course. The 1-year amputation-free survival rate for patients diagnosed with CLI is 45%; the mortality rate is approximately 25% and may be as high as 45% in those who have undergone amputation. Management of this end-stage disease process consumes a significant amount of healthcare resources. Clearly, new therapeutic approaches are required.
Hepatocyte growth factor (HGF) has been shown to be a potent angiogenic growth factor stimulating the growth of endothelial cells and migration of vascular smooth muscle cells. Because of its pluripotent capabilities, increasing the availability of HGF in ischemic tissues to achieve therapeutic angiogenesis has been a growing area of research.
This study will use VM202, which is a DNA plasmid that contains novel genomic cDNA hybrid human HGF coding sequence (HGF-X7) expressing two isoforms of HGF, HGF 728 and HGF 723. As there are currently no approved drugs that can reverse CLI and as most patients have exhausted surgical and endovascular intervention options, inducing angiogenesis in the affected limb with VM202 may result in an increase in tissue perfusion, which, in turn improve wound healing, reduce pain and improve limb salvage rates.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Low Dose VM202 | Experimental | Patients in this group received 8mg total of VM202. Day 0: 4mg of VM202 (16 injections of 0.5ml of VM202) Day14: 4mg of VM202 (16 injections of 0.5ml of VM202) Day 28: 16 injections of 0.5ml of normal saline Day 42: 16 injections of 0.5ml of normal saline |
|
| High Dose VM202 | Experimental | Patients in this treatment group received a total of 16mg VM202. Day 0: 4mg of VM202 (16 injections of 0.5ml of VM202) Day14: 4mg of VM202 (16 injections of 0.5ml of VM202) Day 28: 4mg of VM202 (16 injections of 0.5ml of VM202) Day42: 4mg of VM202 (16 injections of 0.5ml of VM202) |
|
| Placebo | Sham Comparator | Patients in this group received a total of 8ml normal saline. Day 0: 16 injections of 0.5ml of normal saline Day 14: 16 injections of 0.5ml of normal saline Day 28: 16 injections of 0.5ml of normal saline Day 42: 16 injections of 0.5ml of normal saline |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Low Dose VM202 | Biological | Day 0: 4mg of VM202 (16 injections of 0.5ml of VM202) Day14: 4mg of VM202 (16 injections of 0.5ml of VM202) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events Following Intramuscular Administration of 8 and 16 mg Engensis (VM202) or Placebo in Subjects With Critical Limb Ischemia. | The number of participants with treatment-emergent adverse events (TEAEs), defined as adverse events occurring after the first injection of Engensis (VM202), was assessed in moderate or high-risk Critical Limb Ischemia subjects. | Baseline - Days 0, 14, 28, 42, 49, 90, 180, 270 and 365 |
| Change From Baseline in Visual Analog Scale (VAS) for Pain | The Visual Analog Scale (VAS) for Pain scoring instrument is a 10 cm line, oriented horizontally, with the left end score of "0" indicating "no pain", and the right end score of "10" representing "pain as bad as it can be" | Days 0, 90, 180, 270, and 365 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Tissue Oxygenation (TcPO2) for the Dorsal Surface of the Foot Following Engensis (VM202) or Placebo | Tissue Oxygenation (TcPO2) measurement is reported for the dorsum of the foot. The change in baseline for the TcPO2 measured in the dorsal surface of the foot results are reported for each of the 3 study groups: 8 mg, or 16 mg for the Engensis (VM202) group, or the Placebo group. Because of the indication being peripheral vascular disease, the dorsal surface of the foot was decided by the sponsor to be a good representative of the lower extremity for any of the other measured sites. |
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Inclusion Criteria:
Male or female, between 18 and 90 years of age;
Diagnosis of critical limb ischemia (Rutherford Class 4 or 5), including:
Poor or suboptimal candidate for bypass graft surgery or percutaneous angioplasty;
Pain at rest, and/or ischemic ulcers, and/or focal gangrene (< 3 cm2) for a minimum of 2 weeks,
Significant stenosis (≥ 75%) of one or more of the following arteries: superficial femoral, popliteal, or two or more infra-popliteal arteries as verified by angiography within 12 months prior to enrollment;
Be willing to maintain current drug therapy for peripheral arterial disease throughout the course of the study including an anti-platelet and statin treatment unless not tolerated;
Clinically stable on optimized medical regimen for >30 days
Be capable of understanding and complying with the protocol and signing the informed consent document prior to being subjected to any study related procedures;
Women who are surgically sterile or at least 1 year postmenopausal or who have been practicing adequate contraception for at least 12 weeks prior to entering the study. If the subject is of child-bearing potential, she must have a negative urine pregnancy test result prior to study enrollment and must agree to repeat pregnancy screening tests during the study. If the subject or the subject's partner(s) is of child bearing potential, the subject and the subject's partner(s) must agree to use a "double barrier" method of birth control while participating in this study.
Exclusion Criteria:
Subjects who have undergone a successful revascularization procedure or sympathectomy within 12 weeks prior to study entry. A clinically unsuccessful revascularization procedure is defined as one in which:
Subjects that will require an amputation in the target leg within 4 weeks of randomization;
Subjects with evidence of active infection (e.g., cellulitis, osteomyelitis) or deep ulceration exposing bone or tendon in the extremity planned for treatment;
Heart Failure with a NYHA classification of III or IV;
Stroke (NIH scale >2) or myocardial infarction within last 3 months;
Unstable angina
Uncontrolled hypertension defined as sustained systolic blood pressure (SBP) > 200 mmHg or diastolic BP (DBP) > 110 mmHg at baseline/screening evaluation;
Ophthalmologic conditions pertinent to proliferative retinopathy or conditions that preclude standard ophthalmologic examination;
Inflammatory disorder of the blood vessels (inflammatory angiopathy, such as Buerger's disease);
Subjects with advanced liver disease including decompensated cirrhosis, jaundice, ascites or bleeding varices;
Subjects currently receiving immunosuppressive medications chemotherapy, or radiation therapy;
Positive HIV or HTLV at screening;
Active Hepatitis B or C infection as determined by Hepatitis B surface antibody (HBsAb), Hepatitis B core antibody (IgG and IgM; HBcAb), Hepatitis B surface antigen (HBsAg) and Hepatitis C antibodies (Anti-HCV), at Screening;
Specific laboratory values at Screening including: Hemoglobin < 8.0 g/dL, WBC < 3,000 cells per microliter, platelet count <75,000/mm3, AST and/or ALT > 3 times the upper limit of normal or any other clinically significant lab abnormality which in the opinion of the investigator should be exclusionary;
Patients with a recent history (< 5 years) of or new screening finding of malignant neoplasm except basal cell carcinoma or squamous cell carcinoma of the skin (if excised and no evidence of recurrence); patients with family history of colon cancer in any first degree relative are excluded unless they have undergone a colonoscopy in the last 12 months with negative findings;
Elevated PSA unless prostate cancer has been excluded;
Subjects with any co- morbid conditions likely to interfere with assessment of safety or efficacy or with an estimated life expectancy of less than 6 months
Subjects requiring > 81 mg daily of acetylsalicylic acid; If > 81 mg are taken at screening, subjects may be enrolled if willing/able to switch to another medication;
Subjects requiring regular COX-2 inhibitor drug(s) or high dose steroids (excepting inhaled steroids);
Major psychiatric disorder in past 6 months;
History of drug or alcohol abuse / dependence in the past 2 years;
Use of an investigational drug or treatment in past 12 months; concurrent participation in investigational protocol or unapproved therapeutics and
Unable or unwilling to give informed consent.
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| Name | Affiliation | Role |
|---|---|---|
| Emerson Perin, MD | Texas Heart Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cardiology PC | Birmingham | Alabama | 35211 | United States | ||
| Vascular and Interventional Specialist of Orange County |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26649448 | Background | Kibbe MR, Hirsch AT, Mendelsohn FO, Davies MG, Pham H, Saucedo J, Marston W, Pyun WB, Min SK, Peterson BG, Comerota A, Choi D, Ballard J, Bartow RA, Losordo DW, Sherman W, Driver V, Perin EC. Safety and efficacy of plasmid DNA expressing two isoforms of hepatocyte growth factor in patients with critical limb ischemia. Gene Ther. 2016 Mar;23(3):306-12. doi: 10.1038/gt.2015.110. Epub 2015 Dec 8. |
| Label | URL |
|---|---|
| Plasmid DNA of HGF in patients with critical limb ischemia | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Low Dose Engensis (8 mg) | Subjects in this group received 8 mg total of Engensis (VM202) Day 0: 4 mg Engensis (16 injections of 0.5 mL Engensis) Day14: 4 mg Engensis (16 injections of 0.5 mL Engensis) Day 28: 16 injections of 0.5 mL of normal saline Day 42: 16 injections of 0.5 mL of normal saline Low Dose VM202: Day 0: 4mg of VM202 (16 injections of 0.5ml of VM202) Day14: 4mg of VM202 (16 injections of 0.5ml of VM202) Placebo: Day 0: 16 injections of 0.5ml of normal saline Day 14: 16 injections of 0.5ml of normal saline Day 28: 16 injections of 0.5ml of normal saline Day 42: 16 injections of 0.5ml of normal saline |
| 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 21, 2011 | Nov 17, 2023 |
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| High Dose VM202 | Biological | Day 0: 4mg of VM202 (16 injections of 0.5ml of VM202) Day 14: 4mg of VM202 (16 injections of 0.5ml of VM202) Day 28: 4mg of VM202 (16 injections of 0.5ml of VM202) Day 42: 4mg of VM202 (16 injections of 0.5ml of VM202) |
|
|
| Placebo | Other | Day 0: 16 injections of 0.5ml of normal saline Day 14: 16 injections of 0.5ml of normal saline Day 28: 16 injections of 0.5ml of normal saline Day 42: 16 injections of 0.5ml of normal saline |
|
|
| Day 0 to Days 180, 270, and 365 |
| Change From Baseline in Hemodynamic Assessment for Ankle Brachial-Index (mmHg) for the Index Leg | Change in the Resting Ankle-Brachial Index (ABI) from Baseline (Day 0) for the Index Leg to Days 180, 270, and 365. Note that by default, Day 0 has no change from baseline. Days 28 and 90 time point data was not included,as they were not relevant to assess efficacy, because of the delayed effect of Engensis, the investigational product. | Days 0, 28, 90, 180, 270, and 365 |
| Change From Baseline in Perfusion of the Occluded Target Artery by Magnetic Resonance Angiogram (MRA) | The quantitative blood flow of the occluded target artery and the volumetric analysis of the newly developed artery by Magnetic Resonance Angiogram (MRA) were recorded. Note that "no change from baseline table of data" is not presented because there was only one subject with both a Baseline and Post Treatment value for Magnetic Resonance Angiogram (MRA) measurement. | Day 0 to Days 180 and 270 |
| Subjects With 100% Wound Healing | The length and width (in cm) was based on photographs and measurements of ulcers. If a ulcer was determined to be 100% healed, the area of the ulcer was set to 0 | Days 0, 14, 28, 42, 49, 90, 180, 270, and 365 |
| Change From Baseline in the Vascular Quality of Life Total Score | The Vascular Quality of Life Total Score (VascuQol) questionnaire has 25 questions that reviewed five domains: activity level (8 items), symptoms (4 items), pain (4 items), emotional (7 items), and social (2 items). The total score is the total of the non-missing scored divided by the number of responded questions. The Vascular Quality of Life Total Score (VascuQol) scale is a 7-point scale with "1" as the worst change from baseline score, and "7" is the least change from baseline score. | Days 0, 90, 270, and 365 |
| Number of Subjects With Major, Lower Leg, Amputations During the Trial | The number and percentage of subjects with major amputations during the trial | Day 0 through Day 365 |
| The Number of Deaths During the Trial | The number and percentage of subjects who died during the trial | Day 0 to Day 365 |
| Change From Baseline in Visual Analog Scale (VAS) for Pain at 9 Months- by Sex | The VAS scoring instrument is a 10 cm line, oriented horizontally, with the left end indicating "no pain" (score = 0 mm, better outcome) and the right end representing "pain as bad as it can be (score = 100 mm, worse outcome). | Days 0 (baseline), 9 months (Day 270) |
| Change From Baseline in Visual Analog Scale (VAS) for Pain at 9 Months- by Renal Dysfunction Status | The VAS scoring instrument is a 10 cm line, oriented horizontally, with the left end indicating "no pain" (score = 0 mm, better outcome) and the right end representing "pain as bad as it can be (score = 100 mm, worse outcome). | Days 0 (baseline), 9 months (Day 270) |
| Change From Baseline in Visual Analog Scale (VAS) for Pain at 9 Months- by Diabetes Status | The VAS scoring instrument is a 10 cm line, oriented horizontally, with the left end indicating "no pain" (score = 0 mm, better outcome) and the right end representing "pain as bad as it can be (score = 100 mm, worse outcome). | Days 0 (baseline), 9 months (Day 270) |
| Orange |
| California |
| 92868 |
| United States |
| Northwestern Memorial Hospital | Chicago | Illinois | 60611 | United States |
| St. Vincent Medical Group | Indianapolis | Indiana | 46290 | United States |
| Boston University School of Medicine | Boston | Massachusetts | 02118 | United States |
| University of Minnesota | Minneapolis | Minnesota | 55454 | United States |
| Saint Louis University | St Louis | Missouri | 63110 | United States |
| UNC School of Medicine | Chapel Hill | North Carolina | 27599 | United States |
| Jobst Vascular | Toledo | Ohio | 43506 | United States |
| University of Oklahoma HSC | Oklahoma City | Oklahoma | 73104 | United States |
| Texas Heart Institute | Houston | Texas | 77030 | United States |
| The Methodist Hospital | Houston | Texas | 77030 | United States |
| University of Utah | Salt Lake City | Utah | 84132 | United States |
| Seoul National University | Seoul | Jongno-gu | 110-744 | South Korea |
| Yonsei University Health System. Severance Cardiovascular Hospital | Seoul | Seodaemun-gu | 120-752 | South Korea |
| Ewha Womans University Medical Center | Seoul | YangCheon-ku | 158-710 | South Korea |
| FG001 | High Dose Engensis (16 mg) | Subjects in this treatment group received a total of 16 mg Engensis (VM202) Day 0: 4 mg Engensis (16 injections of 0.5 mL Engensis) Day14: 4 mg of Engensis (16 injections of 0.5 mL Engensis) Day 28: 4 mg of Engensis (16 injections of 0.5 mL Engensis) Day42: 4 mg of Engensis (16 injections of 0.5 mL Engensis) High Dose Engensis: Day 0: 4 mg Engensis (16 injections of 0.5 mL Engensis) Day 14: 4 mg Engensis (16 injections of 0.5 mL Engensis) Day 28: 4 mg Engensis (16 injections of 0.5 mL Engensis) Day 42: 4 mg Engensis (16 injections of 0.5 mL Engensis) |
| FG002 | Placebo | Subjects in this group will receive a total of 8ml normal saline. Day 0: 16 injections of 0.5 mL of normal saline Day 14: 16 injections of 0.5 mL of normal saline Day 28: 16 injections of 0.5 mL of normal saline Day 42: 16 injections of 0.5 mL of normal saline Placebo: Day 0: 16 injections of 0.5 mL of normal saline Day 14: 16 injections of 0.5 mL of normal saline Day 28: 16 injections of 0.5 mL of normal saline Day 42: 16 injections of 0.5 mL of normal saline |
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| NOT COMPLETED |
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Safety population
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| ID | Title | Description |
|---|---|---|
| BG000 | Engensis 8 mg | Subjects in this group received 8 mg total of Engensis (VM202) Day 0: 4 mg Engensis (16 injections of 0.5 mL, 0.25 mg Engensis) Day14: 4 mg Engensis (16 injections of 0.5 mL. 0.25 mg Engensis) Day 28: 16 injections of 0.5 mL of normal saline Day 42: 16 injections of 0.5 mL of normal saline |
| BG001 | Engensis 16 mg | Subjects in this group received a total of 16 mg Engensis (VM202) Day 0: 4 mg Engensis (16 injections of 0.5 mL, 0.25 mg Engensis) Day14: 4 mg of Engensis (16 injections of 0.5 mL, 0.25 mg Engensis) Day 28: 4 mg of Engensis (16 injections of 0.5 mL, 0.25 mg Engensis) Day42: 4 mg of Engensis (16 injections of 0.5 mL, 0.25 mg Engensis) |
| BG002 | Placebo | Subjects in this group received a total of 8 mL normal saline. Day 0: 16 injections of 0.5 mL of normal saline Day 14: 16 injections of 0.5 mL of normal saline Day 28: 16 injections of 0.5 mL of normal saline Day 42: 16 injections of 0.5 mL of normal saline |
| BG003 | 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, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
|
| 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 | Number of Participants With Treatment-emergent Adverse Events Following Intramuscular Administration of 8 and 16 mg Engensis (VM202) or Placebo in Subjects With Critical Limb Ischemia. | The number of participants with treatment-emergent adverse events (TEAEs), defined as adverse events occurring after the first injection of Engensis (VM202), was assessed in moderate or high-risk Critical Limb Ischemia subjects. | The Safety Population included all subjects who received at least 1 study drug injection of Engensis or Placebo | Posted | Count of Participants | Participants | Baseline - Days 0, 14, 28, 42, 49, 90, 180, 270 and 365 |
|
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| |||||||||||||||||||||||||||||||||||
| Primary | Change From Baseline in Visual Analog Scale (VAS) for Pain | The Visual Analog Scale (VAS) for Pain scoring instrument is a 10 cm line, oriented horizontally, with the left end score of "0" indicating "no pain", and the right end score of "10" representing "pain as bad as it can be" | The Per-Protocol (PP) Population included all subjects who received the correct dose of study drug, had the 9-month (Day 270) VAS assessment, and did not have any protocol violations or major deviations. The PP Population was determined in a blinded review before database lock. Subjects were analyzed according to the treatment to which they were randomized. Primary efficacy analyses were performed on the PP population. | Posted | Mean | Standard Deviation | units on a scale | Days 0, 90, 180, 270, and 365 |
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| Secondary | Change From Baseline in Tissue Oxygenation (TcPO2) for the Dorsal Surface of the Foot Following Engensis (VM202) or Placebo | Tissue Oxygenation (TcPO2) measurement is reported for the dorsum of the foot. The change in baseline for the TcPO2 measured in the dorsal surface of the foot results are reported for each of the 3 study groups: 8 mg, or 16 mg for the Engensis (VM202) group, or the Placebo group. Because of the indication being peripheral vascular disease, the dorsal surface of the foot was decided by the sponsor to be a good representative of the lower extremity for any of the other measured sites. | The Intent-to-Treat population included all subjects who were randomized regardless of whether treatment was received | Posted | Mean | Standard Deviation | mmHg | Day 0 to Days 180, 270, and 365 |
| ||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Hemodynamic Assessment for Ankle Brachial-Index (mmHg) for the Index Leg | Change in the Resting Ankle-Brachial Index (ABI) from Baseline (Day 0) for the Index Leg to Days 180, 270, and 365. Note that by default, Day 0 has no change from baseline. Days 28 and 90 time point data was not included,as they were not relevant to assess efficacy, because of the delayed effect of Engensis, the investigational product. | Intent-to-treat population: includes all subjects who were randomized regardless of whether treatment was received | Posted | Mean | Standard Deviation | mm Hg | Days 0, 28, 90, 180, 270, and 365 |
| ||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Perfusion of the Occluded Target Artery by Magnetic Resonance Angiogram (MRA) | The quantitative blood flow of the occluded target artery and the volumetric analysis of the newly developed artery by Magnetic Resonance Angiogram (MRA) were recorded. Note that "no change from baseline table of data" is not presented because there was only one subject with both a Baseline and Post Treatment value for Magnetic Resonance Angiogram (MRA) measurement. | ITT population or Per protocol population - Note: Only 1 subject had both a baseline and post-treatment MRA performed. Unfortunately, no quantitative perfusion data were collected. | Posted | Day 0 to Days 180 and 270 |
| |||||||||||||||||||||||||||||||||||||||
| Secondary | Subjects With 100% Wound Healing | The length and width (in cm) was based on photographs and measurements of ulcers. If a ulcer was determined to be 100% healed, the area of the ulcer was set to 0 | Intent-to-Treat population | Posted | Count of Participants | Participants | Days 0, 14, 28, 42, 49, 90, 180, 270, and 365 |
| |||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in the Vascular Quality of Life Total Score | The Vascular Quality of Life Total Score (VascuQol) questionnaire has 25 questions that reviewed five domains: activity level (8 items), symptoms (4 items), pain (4 items), emotional (7 items), and social (2 items). The total score is the total of the non-missing scored divided by the number of responded questions. The Vascular Quality of Life Total Score (VascuQol) scale is a 7-point scale with "1" as the worst change from baseline score, and "7" is the least change from baseline score. | Per-protocol population | Posted | Mean | Standard Deviation | score on a scale | Days 0, 90, 270, and 365 |
| ||||||||||||||||||||||||||||||||||||
| Secondary | Number of Subjects With Major, Lower Leg, Amputations During the Trial | The number and percentage of subjects with major amputations during the trial | Intent-to-treat population | Posted | Count of Participants | Participants | Day 0 through Day 365 |
| |||||||||||||||||||||||||||||||||||||
| Secondary | The Number of Deaths During the Trial | The number and percentage of subjects who died during the trial | Intent-to-treat population | Posted | Count of Participants | Participants | Day 0 to Day 365 |
| |||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Visual Analog Scale (VAS) for Pain at 9 Months- by Sex | The VAS scoring instrument is a 10 cm line, oriented horizontally, with the left end indicating "no pain" (score = 0 mm, better outcome) and the right end representing "pain as bad as it can be (score = 100 mm, worse outcome). | The Per-Protocol (PP) Population included all subjects who received the correct dose of study drug, had the 9-month (Day 270) VAS assessment, and did not have any protocol violations or major deviations. The PP Population was determined in a blinded review before database lock. Subjects were analyzed according to the treatment to which they were randomized. Primary efficacy analyses were performed on the PP population. | Posted | Mean | Standard Deviation | units on a scale | Days 0 (baseline), 9 months (Day 270) |
| ||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Visual Analog Scale (VAS) for Pain at 9 Months- by Renal Dysfunction Status | The VAS scoring instrument is a 10 cm line, oriented horizontally, with the left end indicating "no pain" (score = 0 mm, better outcome) and the right end representing "pain as bad as it can be (score = 100 mm, worse outcome). | The Per-Protocol (PP) Population included all subjects who received the correct dose of study drug, had the 9-month (Day 270) VAS assessment, and did not have any protocol violations or major deviations. The PP Population was determined in a blinded review before database lock. Subjects were analyzed according to the treatment to which they were randomized. Primary efficacy analyses were performed on the PP population. | Posted | Mean | Standard Deviation | units on a scale | Days 0 (baseline), 9 months (Day 270) |
| ||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Visual Analog Scale (VAS) for Pain at 9 Months- by Diabetes Status | The VAS scoring instrument is a 10 cm line, oriented horizontally, with the left end indicating "no pain" (score = 0 mm, better outcome) and the right end representing "pain as bad as it can be (score = 100 mm, worse outcome). | The Per-Protocol (PP) Population included all subjects who received the correct dose of study drug, had the 9-month (Day 270) VAS assessment, and did not have any protocol violations or major deviations. The PP Population was determined in a blinded review before database lock. Subjects were analyzed according to the treatment to which they were randomized. Primary efficacy analyses were performed on the PP population. | Posted | Mean | Standard Deviation | units on a scale | Days 0 (baseline), 9 months (Day 270) |
|
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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 | Engensis 8 mg | Subjects in this group received 8 mg total of Engensis (VM202) Day 0: 4 mg Engensis (16 injections of 0.5 mL, 0.25 mg Engensis) Day14: 4 mg Engensis (16 injections of 0.5 mL. 0.25 mg Engensis) Day 28: 16 injections of 0.5 mL of normal saline Day 42: 16 injections of 0.5 mL of normal saline | 1 | 21 | 9 | 21 | 18 | 21 |
| EG001 | Engensis 16 mg | Subjects in this group received a total of 16 mg Engensis (VM202) Day 0: 4 mg Engensis (16 injections of 0.5 mL, 0.25 mg Engensis) Day14: 4 mg of Engensis (16 injections of 0.5 mL, 0.25 mg Engensis) Day 28: 4 mg of Engensis (16 injections of 0.5 mL, 0.25 mg Engensis) Day42: 4 mg of Engensis (16 injections of 0.5 mL, 0.25 mg Engensis) | 0 | 20 | 11 | 20 | 18 | 20 |
| EG002 | Placebo | Subjects in this group received a total of 8 mL normal saline. Day 0: 16 injections of 0.5 mL of normal saline Day 14: 16 injections of 0.5 mL of normal saline Day 28: 16 injections of 0.5 mL of normal saline Day 42: 16 injections of 0.5 mL of normal saline | 1 | 11 | 6 | 11 | 10 | 11 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Peripheral arterial occlusive disease | Vascular disorders | MedDRA | Non-systematic Assessment |
| |
| Peripheral ischaemia | Vascular disorders | MedDRA | Non-systematic Assessment |
| |
| Arterial thrombosis limb | Vascular disorders | MedDRA | Non-systematic Assessment |
| |
| Gangrene | Infections and infestations | MedDRA | Non-systematic Assessment |
| |
| Osteomyelitis | Infections and infestations | MedDRA | Non-systematic Assessment |
| |
| Renal failure acute | Renal and urinary disorders | MedDRA | Non-systematic Assessment |
| |
| Acute myocardial infarction | Cardiac disorders | MedDRA | Non-systematic Assessment |
| |
| Arterial stenosis limb | Vascular disorders | MedDRA | Non-systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA | Non-systematic Assessment |
| |
| Femoral artery occlusion | Vascular disorders | MedDRA | Non-systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA | Non-systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA | Non-systematic Assessment |
| |
| Ischaemic limb pain | Vascular disorders | MedDRA | Non-systematic Assessment |
| |
| Celulitis | Infections and infestations | MedDRA | Non-systematic Assessment |
| |
| Cystitis | Infections and infestations | MedDRA | Non-systematic Assessment |
| |
| Infection | Infections and infestations | MedDRA | Non-systematic Assessment |
| |
| Localised infection | Infections and infestations | MedDRA | Non-systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA | Non-systematic Assessment |
| |
| Staphylococcal sepsis | Infections and infestations | MedDRA | Non-systematic Assessment |
| |
| Wound infection | Infections and infestations | MedDRA | Non-systematic Assessment |
| |
| Renal failure chronic | Renal and urinary disorders | MedDRA | Systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MedDRA | Non-systematic Assessment |
| |
| Cardiac failure chronic | Cardiac disorders | MedDRA | Non-systematic Assessment |
| |
| Chest pain | General disorders | MedDRA | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA | Non-systematic Assessment |
| |
| Device occlusion | General disorders | MedDRA | Non-systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA | Non-systematic Assessment |
| |
| Haemorrhagic anaemia | Blood and lymphatic system disorders | MedDRA (23.0) | Non-systematic Assessment |
| |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA (23.0) | Non-systematic Assessment |
| |
| Lower gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA (23.0) | Non-systematic Assessment |
| |
| Pancreatitis | Gastrointestinal disorders | MedDRA | Non-systematic Assessment |
| |
| Graft complication | Injury, poisoning and procedural complications | MedDRA | Non-systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA | Non-systematic Assessment |
| |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA | Non-systematic Assessment |
| |
| Skin ulcer | Skin and subcutaneous tissue disorders | MedDRA | Non-systematic Assessment |
| |
| Renal failure acute | Renal and urinary disorders | MedDRA (23.0) | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cellulitis | Infections and infestations | MedDRA | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA | Non-systematic Assessment |
| |
| Wound infection | Infections and infestations | MedDRA | Non-systematic Assessment |
| |
| Cystitis | Infections and infestations | MedDRA | Non-systematic Assessment |
| |
| Fungal skin infection | Infections and infestations | MedDRA | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA | Non-systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA | Non-systematic Assessment |
| |
| Tooth abscess | Infections and infestations | MedDRA | Non-systematic Assessment |
| |
| Upper respiratory infection | Infections and infestations | MedDRA | Non-systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA | Non-systematic Assessment |
| |
| Candidiasis | Infections and infestations | MedDRA | Non-systematic Assessment |
| |
| Clostridium difficile colitis | Infections and infestations | MedDRA | Non-systematic Assessment |
| |
| Labyrinithitis | Infections and infestations | MedDRA | Non-systematic Assessment |
| |
| Onychomycosis | Infections and infestations | MedDRA | Non-systematic Assessment |
| |
| Otitis media | Infections and infestations | MedDRA | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA | Non-systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDRA (23.0) | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (23.0) | Non-systematic Assessment |
| |
| Hiatus hernia | Gastrointestinal disorders | MedDRA (23.0) | Non-systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | MedDRA (23.0) | Non-systematic Assessment |
| |
| Dental caries | Gastrointestinal disorders | MedDRA (23.0) | Non-systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA (23.0) | Non-systematic Assessment |
| |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA (23.0) | Non-systematic Assessment |
| |
| Inflammatory bowel disease | Gastrointestinal disorders | MedDRA (23.0) | Non-systematic Assessment |
| |
| Oesophagitis | Gastrointestinal disorders | MedDRA (23.0) | Non-systematic Assessment |
| |
| Pancreatitis | Gastrointestinal disorders | MedDRA (23.0) | Non-systematic Assessment |
|
Not provided
Not provided
| 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 | Oct 2, 2013 | Nov 17, 2023 | SAP_001.pdf |
| ID | Term |
|---|---|
| D000089802 | Chronic Limb-Threatening Ischemia |
| ID | Term |
|---|---|
| D058729 | Peripheral Arterial Disease |
| D050197 | Atherosclerosis |
| D001161 | Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D016491 | Peripheral Vascular Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D007511 | Ischemia |
Not provided
Not provided
| ID | Term |
|---|---|
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |
Not provided
Not provided
| Male |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| United States |
|
| Title | Measurements |
|---|---|
|
| Gangrene |
|
| Urinary tract infection |
|
| Wound infection |
|
| Cystitis |
|
| Sinusitis |
|
| Tooth Abscess |
|
| Gastrointestinal disorders |
|
| Diarrhoea |
|
| Constipation |
|
| Nausea |
|
| Gastritis |
|
| Vomiting |
|
| Hiatus hernia |
|
| General disorders and administration site conditions |
|
| Oedema peripheral |
|
| Injection site haematoma |
|
| Pyrexia |
|
| Musculoskeletal and connective tissue disorders |
|
| Pain in extremity |
|
| Muscle spasms |
|
| Arthralgia |
|
| Vascular disorders |
|
| Peripheral arterial occlusive disease |
|
| Arterial thrombosis limb |
|
| Metabolism and nutrition disorders |
|
| Hypoglycaemia |
|
| Decreased appetite |
|
| Hyperglycaemia |
|
| Skin and subcutaneous tissue disorders |
|
| skin ulcer |
|
| blister |
|
| Injury, poisoning and procedureal complications |
|
| Contusion |
|
| Procedural pain |
|
| Limb injury |
|
| Nervous system disorders |
|
| Headache |
|
| Phantom pain |
|
| Dizziness |
|
| Renal and urinary disorders |
|
| Renal failure acute |
|
| Respiratory, thoracic and mediastinal disorders |
|
| Chronic obstructive pulmonary disease |
|
| Dyspnoea |
|
| Psychiatric disorders |
|
| Anxiety |
|
| Mental status changes |
|
| Depression |
|
| Blood and lymphatic system disorders |
|
| Anaemia |
|
| Cardiac disorders |
|
| Acute myocardial infarction |
|
| OG002 | Placebo | Subjects received a total of 8 mL normal saline. Day 0: 16 injections of 0.5 mL of normal saline Day 14: 16 injections of 0.5 mL of normal saline Day 28: 16 injections of 0.5 mL of normal saline Day 42: 16 injections of 0.5 mL of normal saline |
|
|
| OG002 | Placebo | Subjects received a total of 8 mL normal saline. Day 0: 16 injections of 0.5 mL of normal saline Day 14: 16 injections of 0.5 mL of normal saline Day 28: 16 injections of 0.5 mL of normal saline Day 42: 16 injections of 0.5 mL of normal saline |
|
|
Subjects received a total of 8 mL normal saline. Day 0: 16 injections of 0.5 mL of normal saline Day 14: 16 injections of 0.5 mL of normal saline Day 28: 16 injections of 0.5 mL of normal saline Day 42: 16 injections of 0.5 mL of normal saline |
|
|
| OG002 |
| Placebo |
Subjects in this group received a total of 8 mL normal saline. Day 0: 16 injections of 0.5 mL of normal saline Day 14: 16 injections of 0.5 mL of normal saline Day 28: 16 injections of 0.5 mL of normal saline Day 42: 16 injections of 0.5 mL of normal saline |
|
|
|
|
| Placebo |
Subjects received a total of 8 mL normal saline. Day 0: 16 injections of 0.5 mL of normal saline Day 14: 16 injections of 0.5 mL of normal saline Day 28: 16 injections of 0.5 mL of normal saline Day 42: 16 injections of 0.5 mL of normal saline |
|
|
|
|
| OG002 | Placebo | Subjects in this group will receive a total of 8ml normal saline. Day 0: 16 injections of 0.5 mL of normal saline Day 14: 16 injections of 0.5 mL of normal saline Day 28: 16 injections of 0.5 mL of normal saline Day 42: 16 injections of 0.5 mL of normal saline Placebo: Day 0: 16 injections of 0.5 mL of normal saline Day 14: 16 injections of 0.5 mL of normal saline Day 28: 16 injections of 0.5 mL of normal saline Day 42: 16 injections of 0.5 mL of normal saline |
|
|
| OG002 | Placebo | Subjects received a total of 8 mL normal saline. Day 0: 16 injections of 0.5 mL of normal saline Day 14: 16 injections of 0.5 mL of normal saline Day 28: 16 injections of 0.5 mL of normal saline Day 42: 16 injections of 0.5 mL of normal saline |
|
|
| OG002 | Placebo | Subjects received a total of 8 mL normal saline. Day 0: 16 injections of 0.5 mL of normal saline Day 14: 16 injections of 0.5 mL of normal saline Day 28: 16 injections of 0.5 mL of normal saline Day 42: 16 injections of 0.5 mL of normal saline |
|
|
| OG002 | Placebo | Subjects received a total of 8 mL normal saline. Day 0: 16 injections of 0.5 mL of normal saline Day 14: 16 injections of 0.5 mL of normal saline Day 28: 16 injections of 0.5 mL of normal saline Day 42: 16 injections of 0.5 mL of normal saline |
|
|