Critical Limb Ischemia
Conditions
Keywords
Painful legs, Ischemic legs, Treatment for Claudication, Gene therapy
Brief summary
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.
Detailed description
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.
Interventions
BIOLOGICALLow 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)
BIOLOGICALHigh Dose VM202
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)
OTHERPlacebo
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
Sponsors
Helixmith Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Male or female, between 18 and 90 years of age; * Diagnosis of critical limb ischemia (Rutherford Class 4 or 5), including: * A resting ankle systolic pressure (in either the dorsalis pedis or posterior tibial arteries) of ≤ 70 mmHg in the affected limb; or * A resting toe systolic pressure of ≤ 50 mmHg in the affected limb; or * For patients in which measurement of ankle systolic pressure is not feasible (e.g. vessel calcification and non-compressibility); TcPO2 ≤ 30 mmHg; * 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: * the target vessel re-occludes (≥50%, as verified by a second angiogram. Duplex ultrasonography can be used to determine vessel patency if the patient cannot tolerate a second angiogram), or * the target vessel remains patent, but there is no resolution of symptoms 6 weeks after the procedure (e.g. no evidence of ulcer healing, no improvement in pressures, no reduction in resting pain); * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | Baseline - Days 0, 14, 28, 42, 49, 90, 180, 270 and 365 | 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. |
| Change From Baseline in Visual Analog Scale (VAS) for Pain | Days 0, 90, 180, 270, and 365 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemodynamic Assessment for Ankle Brachial-Index (mmHg) for the Index Leg | Days 0, 28, 90, 180, 270, and 365 | 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. |
| Change From Baseline in Perfusion of the Occluded Target Artery by Magnetic Resonance Angiogram (MRA) | Day 0 to Days 180 and 270 | 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. |
| Subjects With 100% Wound Healing | Days 0, 14, 28, 42, 49, 90, 180, 270, and 365 | 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 |
| Change From Baseline in the Vascular Quality of Life Total Score | Days 0, 90, 270, and 365 | 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. |
| Change From Baseline in Tissue Oxygenation (TcPO2) for the Dorsal Surface of the Foot Following Engensis (VM202) or Placebo | Day 0 to Days 180, 270, and 365 | 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. |
| Change From Baseline in Visual Analog Scale (VAS) for Pain at 9 Months- by Sex | Days 0 (baseline), 9 months (Day 270) | 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). |
| Change From Baseline in Visual Analog Scale (VAS) for Pain at 9 Months- by Renal Dysfunction Status | Days 0 (baseline), 9 months (Day 270) | 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). |
| Change From Baseline in Visual Analog Scale (VAS) for Pain at 9 Months- by Diabetes Status | Days 0 (baseline), 9 months (Day 270) | 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). |
| Number of Subjects With Major, Lower Leg, Amputations During the Trial | Day 0 through Day 365 | The number and percentage of subjects with major amputations during the trial |
| The Number of Deaths During the Trial | Day 0 to Day 365 | The number and percentage of subjects who died during the trial |
Countries
South Korea, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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 | 21 |
| 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) | 20 |
| 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 | 11 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 1 | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 1 | 1 |
| Overall Study | Non-compliance | 0 | 1 | 0 |
| Overall Study | Other: amputation | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Engensis 8 mg | Engensis 16 mg | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 65.9 years STANDARD_DEVIATION 10.7 | 67.2 years STANDARD_DEVIATION 10.9 | 64.3 years STANDARD_DEVIATION 14.5 | NA years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 7 Participants | 2 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) White | 13 Participants | 11 Participants | 6 Participants | 30 Participants |
| Region of Enrollment South Korea | 2 participants | 1 participants | 2 participants | 1 participants |
| Region of Enrollment United States | 19 participants | 19 participants | 9 participants | 51 participants |
| Sex: Female, Male Female | 7 Participants | 7 Participants | 5 Participants | 19 Participants |
| Sex: Female, Male Male | 14 Participants | 13 Participants | 6 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 21 | 0 / 20 | 1 / 11 |
| other Total, other adverse events | 18 / 21 | 18 / 20 | 10 / 11 |
| serious Total, serious adverse events | 9 / 21 | 11 / 20 | 6 / 11 |
Outcome results
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
Time frame: Days 0, 90, 180, 270, and 365
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose Engensis (8 mg) | Change From Baseline in Visual Analog Scale (VAS) for Pain | Day 270 | -8.2 units on a scale | Standard Deviation 22.3 |
| Low Dose Engensis (8 mg) | Change From Baseline in Visual Analog Scale (VAS) for Pain | Day 180 | -17.2 units on a scale | Standard Deviation 25.6 |
| Low Dose Engensis (8 mg) | Change From Baseline in Visual Analog Scale (VAS) for Pain | Day 90 | -13.0 units on a scale | Standard Deviation 15.1 |
| Low Dose Engensis (8 mg) | Change From Baseline in Visual Analog Scale (VAS) for Pain | Baseline (Day 0) - Actual values only | 40.5 units on a scale | Standard Deviation 31.3 |
| Low Dose Engensis (8 mg) | Change From Baseline in Visual Analog Scale (VAS) for Pain | Day 365 | -17.6 units on a scale | Standard Deviation 30.3 |
| High Dose Engensis (16 mg) | Change From Baseline in Visual Analog Scale (VAS) for Pain | Day 180 | -28.9 units on a scale | Standard Deviation 31.1 |
| High Dose Engensis (16 mg) | Change From Baseline in Visual Analog Scale (VAS) for Pain | Day 90 | -32.7 units on a scale | Standard Deviation 19.8 |
| High Dose Engensis (16 mg) | Change From Baseline in Visual Analog Scale (VAS) for Pain | Baseline (Day 0) - Actual values only | 62.3 units on a scale | Standard Deviation 22.5 |
| High Dose Engensis (16 mg) | Change From Baseline in Visual Analog Scale (VAS) for Pain | Day 270 | -34.5 units on a scale | Standard Deviation 39.6 |
| High Dose Engensis (16 mg) | Change From Baseline in Visual Analog Scale (VAS) for Pain | Day 365 | -29.1 units on a scale | Standard Deviation 21.7 |
| Placebo | Change From Baseline in Visual Analog Scale (VAS) for Pain | Day 365 | -45.8 units on a scale | Standard Deviation 30.8 |
| Placebo | Change From Baseline in Visual Analog Scale (VAS) for Pain | Day 270 | -38.6 units on a scale | Standard Deviation 41.1 |
| Placebo | Change From Baseline in Visual Analog Scale (VAS) for Pain | Baseline (Day 0) - Actual values only | 60.6 units on a scale | Standard Deviation 30.1 |
| Placebo | Change From Baseline in Visual Analog Scale (VAS) for Pain | Day 180 | -29.0 units on a scale | Standard Deviation 28.5 |
| Placebo | Change From Baseline in Visual Analog Scale (VAS) for Pain | Day 90 | -29.0 units on a scale | Standard Deviation 19.9 |
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.
Time frame: Baseline - Days 0, 14, 28, 42, 49, 90, 180, 270 and 365
Population: The Safety Population included all subjects who received at least 1 study drug injection of Engensis or Placebo
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Low Dose Engensis (8 mg) | 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. | Headache | 0 Participants |
| Low Dose Engensis (8 mg) | 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. | Injection site haematoma | 2 Participants |
| Low Dose Engensis (8 mg) | 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. | Hyperglycaemia | 1 Participants |
| Low Dose Engensis (8 mg) | 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. | Nervous system disorders | 1 Participants |
| Low Dose Engensis (8 mg) | 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. | Pyrexia | 0 Participants |
| Low Dose Engensis (8 mg) | 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. | Blood and lymphatic system disorders | 5 Participants |
| Low Dose Engensis (8 mg) | 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. | Limb injury | 1 Participants |
| Low Dose Engensis (8 mg) | 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. | Procedural pain | 3 Participants |
| Low Dose Engensis (8 mg) | 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. | Pain in extremity | 4 Participants |
| Low Dose Engensis (8 mg) | 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. | Cystitis | 0 Participants |
| Low Dose Engensis (8 mg) | 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. | Contusion | 2 Participants |
| Low Dose Engensis (8 mg) | 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. | Muscle spasms | 4 Participants |
| Low Dose Engensis (8 mg) | 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. | Depression | 0 Participants |
| Low Dose Engensis (8 mg) | 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. | Injury, poisoning and procedureal complications | 8 Participants |
| Low Dose Engensis (8 mg) | 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. | Arthralgia | 3 Participants |
| Low Dose Engensis (8 mg) | 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. | Sinusitis | 0 Participants |
| Low Dose Engensis (8 mg) | 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. | blister | 0 Participants |
| Low Dose Engensis (8 mg) | 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. | Vascular disorders | 9 Participants |
| Low Dose Engensis (8 mg) | 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. | Nausea | 2 Participants |
| Low Dose Engensis (8 mg) | 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. | skin ulcer | 4 Participants |
| Low Dose Engensis (8 mg) | 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. | Peripheral arterial occlusive disease | 2 Participants |
| Low Dose Engensis (8 mg) | 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. | Mental status changes | 1 Participants |
| Low Dose Engensis (8 mg) | 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. | Skin and subcutaneous tissue disorders | 8 Participants |
| Low Dose Engensis (8 mg) | 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. | Arterial thrombosis limb | 0 Participants |
| Low Dose Engensis (8 mg) | 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. | Tooth Abscess | 0 Participants |
| Low Dose Engensis (8 mg) | 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. | Decreased appetite | 0 Participants |
| Low Dose Engensis (8 mg) | 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. | Metabolism and nutrition disorders | 5 Participants |
| Low Dose Engensis (8 mg) | 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. | Infections and infestations | 8 Participants |
| Low Dose Engensis (8 mg) | 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. | Hypoglycaemia | 2 Participants |
| Low Dose Engensis (8 mg) | 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. | Anxiety | 2 Participants |
| Low Dose Engensis (8 mg) | 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. | Gastrointestinal disorders | 9 Participants |
| Low Dose Engensis (8 mg) | 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. | Acute myocardial infarction | 0 Participants |
| Low Dose Engensis (8 mg) | 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. | Psychiatric disorders | 4 Participants |
| Low Dose Engensis (8 mg) | 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. | Diarrhoea | 3 Participants |
| Low Dose Engensis (8 mg) | 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. | Cardiac disorders | 3 Participants |
| Low Dose Engensis (8 mg) | 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. | Dyspnoea | 1 Participants |
| Low Dose Engensis (8 mg) | 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. | Constipation | 2 Participants |
| Low Dose Engensis (8 mg) | 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. | Cellulitis | 3 Participants |
| Low Dose Engensis (8 mg) | 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. | Chronic obstructive pulmonary disease | 1 Participants |
| Low Dose Engensis (8 mg) | 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. | Respiratory, thoracic and mediastinal disorders | 6 Participants |
| Low Dose Engensis (8 mg) | 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. | Gastritis | 1 Participants |
| Low Dose Engensis (8 mg) | 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. | Musculoskeletal and connective tissue disorders | 9 Participants |
| Low Dose Engensis (8 mg) | 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. | Renal failure acute | 5 Participants |
| Low Dose Engensis (8 mg) | 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. | Vomiting | 1 Participants |
| Low Dose Engensis (8 mg) | 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. | Gangrene | 0 Participants |
| Low Dose Engensis (8 mg) | 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. | Renal and urinary disorders | 7 Participants |
| Low Dose Engensis (8 mg) | 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. | Hiatus hernia | 0 Participants |
| Low Dose Engensis (8 mg) | 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. | Anaemia | 4 Participants |
| Low Dose Engensis (8 mg) | 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. | Dizziness | 0 Participants |
| Low Dose Engensis (8 mg) | 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. | General disorders and administration site conditions | 12 Participants |
| Low Dose Engensis (8 mg) | 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. | Urinary tract infection | 2 Participants |
| Low Dose Engensis (8 mg) | 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. | Phantom pain | 1 Participants |
| Low Dose Engensis (8 mg) | 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. | Oedema peripheral | 3 Participants |
| Low Dose Engensis (8 mg) | 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. | Wound infection | 1 Participants |
| High Dose Engensis (16 mg) | 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. | Injury, poisoning and procedureal complications | 3 Participants |
| High Dose Engensis (16 mg) | 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. | Urinary tract infection | 1 Participants |
| High Dose Engensis (16 mg) | 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. | Cystitis | 2 Participants |
| High Dose Engensis (16 mg) | 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. | Nausea | 2 Participants |
| High Dose Engensis (16 mg) | 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. | Musculoskeletal and connective tissue disorders | 8 Participants |
| High Dose Engensis (16 mg) | 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. | Renal and urinary disorders | 2 Participants |
| High Dose Engensis (16 mg) | 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. | Infections and infestations | 10 Participants |
| High Dose Engensis (16 mg) | 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. | Cellulitis | 1 Participants |
| High Dose Engensis (16 mg) | 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. | Gangrene | 3 Participants |
| High Dose Engensis (16 mg) | 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. | Wound infection | 2 Participants |
| High Dose Engensis (16 mg) | 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. | Sinusitis | 2 Participants |
| High Dose Engensis (16 mg) | 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. | Tooth Abscess | 0 Participants |
| High Dose Engensis (16 mg) | 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. | Gastrointestinal disorders | 7 Participants |
| High Dose Engensis (16 mg) | 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. | Diarrhoea | 2 Participants |
| High Dose Engensis (16 mg) | 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. | Constipation | 1 Participants |
| High Dose Engensis (16 mg) | 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. | Gastritis | 2 Participants |
| High Dose Engensis (16 mg) | 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. | Vomiting | 1 Participants |
| High Dose Engensis (16 mg) | 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. | Hiatus hernia | 2 Participants |
| High Dose Engensis (16 mg) | 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. | General disorders and administration site conditions | 6 Participants |
| High Dose Engensis (16 mg) | 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. | Oedema peripheral | 2 Participants |
| High Dose Engensis (16 mg) | 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. | Injection site haematoma | 0 Participants |
| High Dose Engensis (16 mg) | 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. | Pyrexia | 2 Participants |
| High Dose Engensis (16 mg) | 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. | Pain in extremity | 6 Participants |
| High Dose Engensis (16 mg) | 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. | Muscle spasms | 0 Participants |
| High Dose Engensis (16 mg) | 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. | Arthralgia | 1 Participants |
| High Dose Engensis (16 mg) | 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. | Vascular disorders | 7 Participants |
| High Dose Engensis (16 mg) | 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. | Peripheral arterial occlusive disease | 4 Participants |
| High Dose Engensis (16 mg) | 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. | Arterial thrombosis limb | 2 Participants |
| High Dose Engensis (16 mg) | 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. | Metabolism and nutrition disorders | 6 Participants |
| High Dose Engensis (16 mg) | 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. | Hypoglycaemia | 2 Participants |
| High Dose Engensis (16 mg) | 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. | Decreased appetite | 2 Participants |
| High Dose Engensis (16 mg) | 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. | Hyperglycaemia | 1 Participants |
| High Dose Engensis (16 mg) | 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. | Skin and subcutaneous tissue disorders | 3 Participants |
| High Dose Engensis (16 mg) | 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. | skin ulcer | 1 Participants |
| High Dose Engensis (16 mg) | 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. | blister | 1 Participants |
| High Dose Engensis (16 mg) | 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. | Contusion | 1 Participants |
| High Dose Engensis (16 mg) | 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. | Procedural pain | 1 Participants |
| High Dose Engensis (16 mg) | 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. | Limb injury | 2 Participants |
| High Dose Engensis (16 mg) | 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. | Nervous system disorders | 7 Participants |
| High Dose Engensis (16 mg) | 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. | Headache | 2 Participants |
| High Dose Engensis (16 mg) | 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. | Phantom pain | 2 Participants |
| High Dose Engensis (16 mg) | 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. | Dizziness | 0 Participants |
| High Dose Engensis (16 mg) | 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. | Renal failure acute | 1 Participants |
| High Dose Engensis (16 mg) | 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. | Respiratory, thoracic and mediastinal disorders | 5 Participants |
| High Dose Engensis (16 mg) | 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. | Chronic obstructive pulmonary disease | 2 Participants |
| High Dose Engensis (16 mg) | 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. | Dyspnoea | 2 Participants |
| High Dose Engensis (16 mg) | 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. | Psychiatric disorders | 5 Participants |
| High Dose Engensis (16 mg) | 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. | Anxiety | 2 Participants |
| High Dose Engensis (16 mg) | 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. | Mental status changes | 2 Participants |
| High Dose Engensis (16 mg) | 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. | Depression | 2 Participants |
| High Dose Engensis (16 mg) | 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. | Blood and lymphatic system disorders | 1 Participants |
| High Dose Engensis (16 mg) | 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. | Anaemia | 1 Participants |
| High Dose Engensis (16 mg) | 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. | Cardiac disorders | 4 Participants |
| High Dose Engensis (16 mg) | 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. | Acute myocardial infarction | 2 Participants |
| Placebo | 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. | Procedural pain | 1 Participants |
| Placebo | 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. | Pyrexia | 1 Participants |
| Placebo | 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. | Infections and infestations | 6 Participants |
| Placebo | 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. | Limb injury | 0 Participants |
| Placebo | 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. | Injection site haematoma | 2 Participants |
| Placebo | 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. | Mental status changes | 0 Participants |
| Placebo | 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. | Nervous system disorders | 3 Participants |
| Placebo | 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. | Oedema peripheral | 1 Participants |
| Placebo | 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. | Cystitis | 0 Participants |
| Placebo | 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. | Headache | 1 Participants |
| Placebo | 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. | General disorders and administration site conditions | 5 Participants |
| Placebo | 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. | Acute myocardial infarction | 0 Participants |
| Placebo | 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. | Phantom pain | 0 Participants |
| Placebo | 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. | Hiatus hernia | 0 Participants |
| Placebo | 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. | Depression | 0 Participants |
| Placebo | 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. | Dizziness | 2 Participants |
| Placebo | 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. | Vomiting | 2 Participants |
| Placebo | 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. | Renal and urinary disorders | 2 Participants |
| Placebo | 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. | Gastritis | 1 Participants |
| Placebo | 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. | Wound infection | 0 Participants |
| Placebo | 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. | Renal failure acute | 0 Participants |
| Placebo | 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. | Nausea | 2 Participants |
| Placebo | 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. | Cardiac disorders | 2 Participants |
| Placebo | 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. | Respiratory, thoracic and mediastinal disorders | 0 Participants |
| Placebo | 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. | Constipation | 3 Participants |
| Placebo | 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. | Blood and lymphatic system disorders | 3 Participants |
| Placebo | 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. | Chronic obstructive pulmonary disease | 0 Participants |
| Placebo | 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. | Diarrhoea | 2 Participants |
| Placebo | 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. | Gangrene | 2 Participants |
| Placebo | 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. | Metabolism and nutrition disorders | 5 Participants |
| Placebo | 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. | Dyspnoea | 0 Participants |
| Placebo | 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. | Hypoglycaemia | 2 Participants |
| Placebo | 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. | Arterial thrombosis limb | 0 Participants |
| Placebo | 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. | Gastrointestinal disorders | 7 Participants |
| Placebo | 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. | Decreased appetite | 2 Participants |
| Placebo | 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. | Urinary tract infection | 2 Participants |
| Placebo | 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. | Hyperglycaemia | 2 Participants |
| Placebo | 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. | Peripheral arterial occlusive disease | 1 Participants |
| Placebo | 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. | Psychiatric disorders | 1 Participants |
| Placebo | 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. | Skin and subcutaneous tissue disorders | 5 Participants |
| Placebo | 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. | Vascular disorders | 4 Participants |
| Placebo | 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. | Tooth Abscess | 2 Participants |
| Placebo | 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. | skin ulcer | 2 Participants |
| Placebo | 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. | Arthralgia | 0 Participants |
| Placebo | 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. | Anaemia | 3 Participants |
| Placebo | 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. | blister | 2 Participants |
| Placebo | 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. | Muscle spasms | 1 Participants |
| Placebo | 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. | Cellulitis | 1 Participants |
| Placebo | 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. | Injury, poisoning and procedureal complications | 4 Participants |
| Placebo | 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. | Pain in extremity | 2 Participants |
| Placebo | 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. | Anxiety | 0 Participants |
| Placebo | 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. | Contusion | 2 Participants |
| Placebo | 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. | Musculoskeletal and connective tissue disorders | 4 Participants |
| Placebo | 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. | Sinusitis | 0 Participants |
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.
Time frame: Days 0, 28, 90, 180, 270, and 365
Population: Intent-to-treat population: includes all subjects who were randomized regardless of whether treatment was received
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose Engensis (8 mg) | Change From Baseline in Hemodynamic Assessment for Ankle Brachial-Index (mmHg) for the Index Leg | Day 270 | 0.006 mm Hg | Standard Deviation 0.181 |
| Low Dose Engensis (8 mg) | Change From Baseline in Hemodynamic Assessment for Ankle Brachial-Index (mmHg) for the Index Leg | Day 180 | 0.009 mm Hg | Standard Deviation 0.13 |
| Low Dose Engensis (8 mg) | Change From Baseline in Hemodynamic Assessment for Ankle Brachial-Index (mmHg) for the Index Leg | Day 365 | -0.012 mm Hg | Standard Deviation 0.123 |
| High Dose Engensis (16 mg) | Change From Baseline in Hemodynamic Assessment for Ankle Brachial-Index (mmHg) for the Index Leg | Day 270 | 0.010 mm Hg | Standard Deviation 0.276 |
| High Dose Engensis (16 mg) | Change From Baseline in Hemodynamic Assessment for Ankle Brachial-Index (mmHg) for the Index Leg | Day 180 | -0.004 mm Hg | Standard Deviation 0.239 |
| High Dose Engensis (16 mg) | Change From Baseline in Hemodynamic Assessment for Ankle Brachial-Index (mmHg) for the Index Leg | Day 365 | -0.011 mm Hg | Standard Deviation 0.277 |
| Placebo | Change From Baseline in Hemodynamic Assessment for Ankle Brachial-Index (mmHg) for the Index Leg | Day 180 | 0.112 mm Hg | Standard Deviation 0.267 |
| Placebo | Change From Baseline in Hemodynamic Assessment for Ankle Brachial-Index (mmHg) for the Index Leg | Day 365 | -0.010 mm Hg | Standard Deviation 0.142 |
| Placebo | Change From Baseline in Hemodynamic Assessment for Ankle Brachial-Index (mmHg) for the Index Leg | Day 270 | 0.042 mm Hg | Standard Deviation 0.216 |
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.
Time frame: Day 0 to Days 180 and 270
Population: 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.
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.
Time frame: Days 0, 90, 270, and 365
Population: Per-protocol population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose Engensis (8 mg) | Change From Baseline in the Vascular Quality of Life Total Score | Day 270 | 0.55 score on a scale | Standard Deviation 1.16 |
| Low Dose Engensis (8 mg) | Change From Baseline in the Vascular Quality of Life Total Score | Day 365 | 0.88 score on a scale | Standard Deviation 1.36 |
| Low Dose Engensis (8 mg) | Change From Baseline in the Vascular Quality of Life Total Score | Baseline (Day 0) - Actual values only | 3.57 score on a scale | Standard Deviation 1.13 |
| Low Dose Engensis (8 mg) | Change From Baseline in the Vascular Quality of Life Total Score | Day 90 | 0.53 score on a scale | Standard Deviation 1.25 |
| High Dose Engensis (16 mg) | Change From Baseline in the Vascular Quality of Life Total Score | Day 270 | 1.26 score on a scale | Standard Deviation 1.53 |
| High Dose Engensis (16 mg) | Change From Baseline in the Vascular Quality of Life Total Score | Day 90 | 1.40 score on a scale | Standard Deviation 1.06 |
| High Dose Engensis (16 mg) | Change From Baseline in the Vascular Quality of Life Total Score | Day 365 | 0.89 score on a scale | Standard Deviation 1.16 |
| High Dose Engensis (16 mg) | Change From Baseline in the Vascular Quality of Life Total Score | Baseline (Day 0) - Actual values only | 3.20 score on a scale | Standard Deviation 1.15 |
| Placebo | Change From Baseline in the Vascular Quality of Life Total Score | Day 365 | 2.07 score on a scale | Standard Deviation 1.23 |
| Placebo | Change From Baseline in the Vascular Quality of Life Total Score | Baseline (Day 0) - Actual values only | 3.50 score on a scale | Standard Deviation 1.6 |
| Placebo | Change From Baseline in the Vascular Quality of Life Total Score | Day 270 | 2.30 score on a scale | Standard Deviation 1.34 |
| Placebo | Change From Baseline in the Vascular Quality of Life Total Score | Day 90 | 2.27 score on a scale | Standard Deviation 1.39 |
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.
Time frame: Day 0 to Days 180, 270, and 365
Population: The Intent-to-Treat population included all subjects who were randomized regardless of whether treatment was received
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose Engensis (8 mg) | Change From Baseline in Tissue Oxygenation (TcPO2) for the Dorsal Surface of the Foot Following Engensis (VM202) or Placebo | Day 270 | 3.6 mmHg | Standard Deviation 19 |
| Low Dose Engensis (8 mg) | Change From Baseline in Tissue Oxygenation (TcPO2) for the Dorsal Surface of the Foot Following Engensis (VM202) or Placebo | Baseline (Day 0) Actual values only | 33.4 mmHg | Standard Deviation 19.4 |
| Low Dose Engensis (8 mg) | Change From Baseline in Tissue Oxygenation (TcPO2) for the Dorsal Surface of the Foot Following Engensis (VM202) or Placebo | Day 365 | 4.1 mmHg | Standard Deviation 20.5 |
| Low Dose Engensis (8 mg) | Change From Baseline in Tissue Oxygenation (TcPO2) for the Dorsal Surface of the Foot Following Engensis (VM202) or Placebo | Day 180 | 5.9 mmHg | Standard Deviation 19.7 |
| High Dose Engensis (16 mg) | Change From Baseline in Tissue Oxygenation (TcPO2) for the Dorsal Surface of the Foot Following Engensis (VM202) or Placebo | Day 270 | 1.7 mmHg | Standard Deviation 17.8 |
| High Dose Engensis (16 mg) | Change From Baseline in Tissue Oxygenation (TcPO2) for the Dorsal Surface of the Foot Following Engensis (VM202) or Placebo | Day 180 | 7.1 mmHg | Standard Deviation 16.6 |
| High Dose Engensis (16 mg) | Change From Baseline in Tissue Oxygenation (TcPO2) for the Dorsal Surface of the Foot Following Engensis (VM202) or Placebo | Baseline (Day 0) Actual values only | 35.0 mmHg | Standard Deviation 18.4 |
| High Dose Engensis (16 mg) | Change From Baseline in Tissue Oxygenation (TcPO2) for the Dorsal Surface of the Foot Following Engensis (VM202) or Placebo | Day 365 | 13.4 mmHg | Standard Deviation 15.6 |
| Placebo | Change From Baseline in Tissue Oxygenation (TcPO2) for the Dorsal Surface of the Foot Following Engensis (VM202) or Placebo | Day 365 | -9.1 mmHg | Standard Deviation 15.3 |
| Placebo | Change From Baseline in Tissue Oxygenation (TcPO2) for the Dorsal Surface of the Foot Following Engensis (VM202) or Placebo | Baseline (Day 0) Actual values only | 40.3 mmHg | Standard Deviation 21.5 |
| Placebo | Change From Baseline in Tissue Oxygenation (TcPO2) for the Dorsal Surface of the Foot Following Engensis (VM202) or Placebo | Day 180 | -9.6 mmHg | Standard Deviation 13.5 |
| Placebo | Change From Baseline in Tissue Oxygenation (TcPO2) for the Dorsal Surface of the Foot Following Engensis (VM202) or Placebo | Day 270 | -7.1 mmHg | Standard Deviation 14.4 |
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).
Time frame: Days 0 (baseline), 9 months (Day 270)
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose Engensis (8 mg) | Change From Baseline in Visual Analog Scale (VAS) for Pain at 9 Months- by Diabetes Status | No Diabetes - Baseline (Day 0) - Actual values only | 56.3 units on a scale | Standard Deviation 34.8 |
| Low Dose Engensis (8 mg) | Change From Baseline in Visual Analog Scale (VAS) for Pain at 9 Months- by Diabetes Status | Has Diabetes - Baseline (Day 0) - Actual values only | 32.6 units on a scale | Standard Deviation 28 |
| Low Dose Engensis (8 mg) | Change From Baseline in Visual Analog Scale (VAS) for Pain at 9 Months- by Diabetes Status | No Diabetes - Day 270 | -16.3 units on a scale | Standard Deviation 24.4 |
| Low Dose Engensis (8 mg) | Change From Baseline in Visual Analog Scale (VAS) for Pain at 9 Months- by Diabetes Status | Has Diabetes - Day 270 | -4.2 units on a scale | Standard Deviation 21.3 |
| High Dose Engensis (16 mg) | Change From Baseline in Visual Analog Scale (VAS) for Pain at 9 Months- by Diabetes Status | No Diabetes - Baseline (Day 0) - Actual values only | 60.8 units on a scale | Standard Deviation 25.2 |
| High Dose Engensis (16 mg) | Change From Baseline in Visual Analog Scale (VAS) for Pain at 9 Months- by Diabetes Status | Has Diabetes - Day 270 | -48.2 units on a scale | Standard Deviation 29.3 |
| High Dose Engensis (16 mg) | Change From Baseline in Visual Analog Scale (VAS) for Pain at 9 Months- by Diabetes Status | Has Diabetes - Baseline (Day 0) - Actual values only | 63.8 units on a scale | Standard Deviation 21.8 |
| High Dose Engensis (16 mg) | Change From Baseline in Visual Analog Scale (VAS) for Pain at 9 Months- by Diabetes Status | No Diabetes - Day 270 | -20.8 units on a scale | Standard Deviation 46.3 |
| Placebo | Change From Baseline in Visual Analog Scale (VAS) for Pain at 9 Months- by Diabetes Status | Has Diabetes - Day 270 | -46.5 units on a scale | Standard Deviation 34.6 |
| Placebo | Change From Baseline in Visual Analog Scale (VAS) for Pain at 9 Months- by Diabetes Status | Has Diabetes - Baseline (Day 0) - Actual values only | 77.0 units on a scale | Standard Deviation 2.8 |
| Placebo | Change From Baseline in Visual Analog Scale (VAS) for Pain at 9 Months- by Diabetes Status | No Diabetes - Day 270 | -33.3 units on a scale | Standard Deviation 51.6 |
| Placebo | Change From Baseline in Visual Analog Scale (VAS) for Pain at 9 Months- by Diabetes Status | No Diabetes - Baseline (Day 0) - Actual values only | 49.7 units on a scale | Standard Deviation 36.8 |
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).
Time frame: Days 0 (baseline), 9 months (Day 270)
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose Engensis (8 mg) | Change From Baseline in Visual Analog Scale (VAS) for Pain at 9 Months- by Renal Dysfunction Status | Has Renal Dysfunction - Baseline (Day 0) - Actual values only | 13.5 units on a scale | Standard Deviation 9 |
| Low Dose Engensis (8 mg) | Change From Baseline in Visual Analog Scale (VAS) for Pain at 9 Months- by Renal Dysfunction Status | Has Renal Dysfunction - Day 270 | -4.0 units on a scale | Standard Deviation 11.1 |
| Low Dose Engensis (8 mg) | Change From Baseline in Visual Analog Scale (VAS) for Pain at 9 Months- by Renal Dysfunction Status | No Renal Dysfunction - Baseline (Day 0) - Actual values only | 47.2 units on a scale | Standard Deviation 31.4 |
| Low Dose Engensis (8 mg) | Change From Baseline in Visual Analog Scale (VAS) for Pain at 9 Months- by Renal Dysfunction Status | No Renal Dysfunction - Day 270 | -9.3 units on a scale | Standard Deviation 24.6 |
| High Dose Engensis (16 mg) | Change From Baseline in Visual Analog Scale (VAS) for Pain at 9 Months- by Renal Dysfunction Status | No Renal Dysfunction - Day 270 | -32.6 units on a scale | Standard Deviation 38.7 |
| High Dose Engensis (16 mg) | Change From Baseline in Visual Analog Scale (VAS) for Pain at 9 Months- by Renal Dysfunction Status | Has Renal Dysfunction - Baseline (Day 0) - Actual values only | 59.0 units on a scale | Standard Deviation 26.8 |
| High Dose Engensis (16 mg) | Change From Baseline in Visual Analog Scale (VAS) for Pain at 9 Months- by Renal Dysfunction Status | No Renal Dysfunction - Baseline (Day 0) - Actual values only | 64.6 units on a scale | Standard Deviation 20.8 |
| High Dose Engensis (16 mg) | Change From Baseline in Visual Analog Scale (VAS) for Pain at 9 Months- by Renal Dysfunction Status | Has Renal Dysfunction - Day 270 | -37.1 units on a scale | Standard Deviation 45.2 |
| Placebo | Change From Baseline in Visual Analog Scale (VAS) for Pain at 9 Months- by Renal Dysfunction Status | No Renal Dysfunction - Day 270 | -46.0 units on a scale | Standard Deviation 35.7 |
| Placebo | Change From Baseline in Visual Analog Scale (VAS) for Pain at 9 Months- by Renal Dysfunction Status | Has Renal Dysfunction - Day 270 | -27.5 units on a scale | Standard Deviation 61.5 |
| Placebo | Change From Baseline in Visual Analog Scale (VAS) for Pain at 9 Months- by Renal Dysfunction Status | No Renal Dysfunction - Baseline (Day 0) - Actual values only | 66.3 units on a scale | Standard Deviation 30.9 |
| Placebo | Change From Baseline in Visual Analog Scale (VAS) for Pain at 9 Months- by Renal Dysfunction Status | Has Renal Dysfunction - Baseline (Day 0) - Actual values only | 52.0 units on a scale | Standard Deviation 38.2 |
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).
Time frame: Days 0 (baseline), 9 months (Day 270)
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose Engensis (8 mg) | Change From Baseline in Visual Analog Scale (VAS) for Pain at 9 Months- by Sex | Males - Baseline (Day 0) - Actual values only | 39.1 units on a scale | Standard Deviation 31.2 |
| Low Dose Engensis (8 mg) | Change From Baseline in Visual Analog Scale (VAS) for Pain at 9 Months- by Sex | Females Day 270 | -14.4 units on a scale | Standard Deviation 24.7 |
| Low Dose Engensis (8 mg) | Change From Baseline in Visual Analog Scale (VAS) for Pain at 9 Months- by Sex | Females - Baseline (Day 0) - Actual values only | 44.3 units on a scale | Standard Deviation 36.2 |
| Low Dose Engensis (8 mg) | Change From Baseline in Visual Analog Scale (VAS) for Pain at 9 Months- by Sex | Males - Day 270 | -6.0 units on a scale | Standard Deviation 22.2 |
| High Dose Engensis (16 mg) | Change From Baseline in Visual Analog Scale (VAS) for Pain at 9 Months- by Sex | Females Day 270 | -25.3 units on a scale | Standard Deviation 43.9 |
| High Dose Engensis (16 mg) | Change From Baseline in Visual Analog Scale (VAS) for Pain at 9 Months- by Sex | Males - Baseline (Day 0) - Actual values only | 70.9 units on a scale | Standard Deviation 14.4 |
| High Dose Engensis (16 mg) | Change From Baseline in Visual Analog Scale (VAS) for Pain at 9 Months- by Sex | Males - Day 270 | -43.8 units on a scale | Standard Deviation 36.2 |
| High Dose Engensis (16 mg) | Change From Baseline in Visual Analog Scale (VAS) for Pain at 9 Months- by Sex | Females - Baseline (Day 0) - Actual values only | 53.7 units on a scale | Standard Deviation 27 |
| Placebo | Change From Baseline in Visual Analog Scale (VAS) for Pain at 9 Months- by Sex | Males - Day 270 | -38.6 units on a scale | Standard Deviation 41.1 |
| Placebo | Change From Baseline in Visual Analog Scale (VAS) for Pain at 9 Months- by Sex | Males - Baseline (Day 0) - Actual values only | 60.6 units on a scale | Standard Deviation 30.1 |
Secondary
Number of Subjects With Major, Lower Leg, Amputations During the Trial
The number and percentage of subjects with major amputations during the trial
Time frame: Day 0 through Day 365
Population: Intent-to-treat population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low Dose Engensis (8 mg) | Number of Subjects With Major, Lower Leg, Amputations During the Trial | 3 Participants |
| High Dose Engensis (16 mg) | Number of Subjects With Major, Lower Leg, Amputations During the Trial | 3 Participants |
| Placebo | Number of Subjects With Major, Lower Leg, Amputations During the Trial | 1 Participants |
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
Time frame: Days 0, 14, 28, 42, 49, 90, 180, 270, and 365
Population: Intent-to-Treat population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Low Dose Engensis (8 mg) | Subjects With 100% Wound Healing | Day 28 | 1 Participants |
| Low Dose Engensis (8 mg) | Subjects With 100% Wound Healing | Day 365 | 5 Participants |
| Low Dose Engensis (8 mg) | Subjects With 100% Wound Healing | Day 42 | 2 Participants |
| Low Dose Engensis (8 mg) | Subjects With 100% Wound Healing | Day 270 | 7 Participants |
| Low Dose Engensis (8 mg) | Subjects With 100% Wound Healing | Day 14 | 1 Participants |
| Low Dose Engensis (8 mg) | Subjects With 100% Wound Healing | Day 49 | 2 Participants |
| Low Dose Engensis (8 mg) | Subjects With 100% Wound Healing | Day 180 | 8 Participants |
| Low Dose Engensis (8 mg) | Subjects With 100% Wound Healing | Day 90 | 4 Participants |
| High Dose Engensis (16 mg) | Subjects With 100% Wound Healing | Day 14 | 3 Participants |
| High Dose Engensis (16 mg) | Subjects With 100% Wound Healing | Day 90 | 4 Participants |
| High Dose Engensis (16 mg) | Subjects With 100% Wound Healing | Day 365 | 3 Participants |
| High Dose Engensis (16 mg) | Subjects With 100% Wound Healing | Day 180 | 4 Participants |
| High Dose Engensis (16 mg) | Subjects With 100% Wound Healing | Day 270 | 3 Participants |
| High Dose Engensis (16 mg) | Subjects With 100% Wound Healing | Day 28 | 4 Participants |
| High Dose Engensis (16 mg) | Subjects With 100% Wound Healing | Day 42 | 4 Participants |
| High Dose Engensis (16 mg) | Subjects With 100% Wound Healing | Day 49 | 4 Participants |
| Placebo | Subjects With 100% Wound Healing | Day 42 | 0 Participants |
| Placebo | Subjects With 100% Wound Healing | Day 365 | 0 Participants |
| Placebo | Subjects With 100% Wound Healing | Day 14 | 0 Participants |
| Placebo | Subjects With 100% Wound Healing | Day 28 | 0 Participants |
| Placebo | Subjects With 100% Wound Healing | Day 270 | 0 Participants |
| Placebo | Subjects With 100% Wound Healing | Day 49 | 0 Participants |
| Placebo | Subjects With 100% Wound Healing | Day 90 | 0 Participants |
| Placebo | Subjects With 100% Wound Healing | Day 180 | 0 Participants |
Secondary
The Number of Deaths During the Trial
The number and percentage of subjects who died during the trial
Time frame: Day 0 to Day 365
Population: Intent-to-treat population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low Dose Engensis (8 mg) | The Number of Deaths During the Trial | 1 Participants |
| High Dose Engensis (16 mg) | The Number of Deaths During the Trial | 0 Participants |
| Placebo | The Number of Deaths During the Trial | 1 Participants |