Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase II, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Efficacy and Safety Study of Different Doses and Schedules of Administration of NV1FGF in Patients With Severe Peripheral Artery Occlusive Disease.
Brief Summary: Peripheral Arterial Occlusive Disease (PAOD) is a condition caused by ischemia in the legs due to atherosclerotic disease affecting the larger arteries of the legs. Chronic PAOD can be regarded as a marker of generalized atherosclerosis. PAOD threatens the survival of an extremity and often causes lifelong disablement from a painful leg. The clinical consequences of PAOD include pain on walking (claudication), pain at rest and loss of tissue integrity in the distal limbs.A variety of medical therapies have been investigated for patients with PAOD. There is currently no evidence to suggest that any medical therapy is effective for patients with rest pain and/or ischemic ulcers.

Also, the use of intramuscular angiogenic VEGF-A gene transfer has recently demonstrated a improvement in clinical and hemodynamic status in patients with severe PAOD


Options:
A: Inclusion Criteria:

* Outpatients with severe Peripheral Artery Occlusive Disease defined as Rutherford's Grade III, category 5 or 6, or Fontaine's stage IV.
* Trophic lesions with no signs of healing (no reduction in ulcer size or depth) for at least 2 weeks prior to first study treatment administration (Day 1).
* Patients with objective evidence of peripheral vascular disease (resting ankle pressure \< 70 mmHg and/or toe pressure \< 50 mmHg, and/or resting ankle-brachial index (ABI) \< 0.4 and/or resting toe-brachial index (TBI) \< 0.3 and/or metatarsal pulse volume recording (PVR) flat or barely pulsatile) in the diseased limb on two consecutive examinations performed at least 1 week apart.
* Demonstration or documentation (historical data not older than 6 months prior to first study treatment administration) of total occlusion of the affected limb of one or more of the iliac, superficial femoral, popliteal and/or one or more infrapopliteal arteries as assessed by angiography.
* Life expectancy \> 6 months from the first study treatment administration.
* Poor/not candidates for revascularization (patients suitable for revascularization but with a high risk of failure/ amputation/ or patients not suitable for revascularization).

Exclusion Criteria:

* Previous or current history of malignant disease. Patients who had successful tumor resection or radio-chemotherapy more than 5 years prior to inclusion in the study and no recurrence will be allowed for inclusion.
* Suspicion of malignant disease (abnormal X ray,positive. stool hemoccult, positive Prostate Specific Antigen , abnormal mammography, papanicolaou smear of Class IV or Class V characterization.
* Lower extremity surgery : bypass/angioplasty of the leg to be treated within 2 months prior to the first administration of study treatment (Day 1).
* Active proliferative retinopathy.
* Buerger's disease
B: Inclusion Criteria:

* Having peripheral artery disease at the stage of Critical Limb Ischemia (CLI) with skin lesions (either ulcer(s) or gangrene);
* With objective evidence of CLI such as ankle systolic pressure \<70 mmHg and/or toe systolic pressure \<50 mmHg or transcutaneous oxygen pressure (TcPO2) \<30 mmHg;
* Unsuitable for standard revascularization of his/her peripheral arterial disease;
* Having a negative screening for cancer.

Exclusion Criteria:

* Previous major amputation on the leg to be treated or planned major amputation within the first month following randomization;
* Known Buerger's disease;
* Successful lower extremity revascularization procedure within 3 months prior randomization;
* Uncontrolled blood pressure defined as systolic blood pressure (SBP) ≥180 mmHg or diastolic blood pressure (DBP) ≥110 mmHg despite adequate antihypertensive treatment;
* Acute cardiovascular events within 3 months prior to randomization;
* Active proliferative retinopathy and severe macular oedema;
* Previous or current history of malignant disease within the past 5 years;
* Previous treatment with systemic angiogenic factors or with stem cells therapy;
* Pregnant or breast-feeding woman or woman of childbearing potential not protected by an effective contraceptive method of birth control. Man not following effective contraceptive method with his partner of childbearing potential during the course of the study.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
C: Inclusion Criteria:

1. Informed consent was to be signed before proceeding with any study procedure.
2. Patients with severe PAD.
3. Trophic lesions with no signs of healing (no reduction in ulcer size or depth) for at least 2 weeks prior to first study treatment administration (Day 1).
4. Patients with objective evidence of peripheral vascular disease in the diseased limb on 2 consecutive examinations performed at least 1 week apart.
5. Demonstration or documentation of total occlusion of the affected limb of one or more of the iliac, superficial femoral, popliteal and/or one or more infrapopliteal arteries as assessed by angiography or magnetic resonance angiography (MRA)
6. Transcutaneous oxygen pressure (TcPO2): mean resting supine TcPO2 of the foot of ≤40 mmHg based on 2 separate measures performed at least 1 week apart
7. Poor/not candidates for revascularization

Exclusion criteria

1. Previous or current history of malignant disease.
2. Positive cancer screening (liver, prostate, colon, cervix, breast, lung)
3. Successful lower extremity surgery (bypass/angioplasty of the leg to be treated) within 3 months prior to the first administration of study treatment \[Day 1\]).
4. Patients planned to undergo amputation of target limb within 1 month following the first administration of study treatment.
5. Patients with a history of severe renal failure.
6. Creatinine \>2.0 mg/dL (176 µmol/L) or estimated creatinine clearance \<30 mL.
7. Serious concomitant medical conditions not adequately controlled (other than severe PAD),
8. Buerger's disease.
9. Patients in dialysis.
10. Active proliferative retinopathy
11. Patients who had a stroke or neurologic deficit presumed to be due to stroke within 3 months prior to the first administration of study treatment.
12. Previous treatment with any angiogenic growth factor.
13. Positive serology for HIV 1 or 2.
14. Participation in clinical trials of non-approved experimental agents within 4 weeks before study entry.
D: Inclusion Criteria:

* Subjects will have one or more clinical indications diagnostic of CLI such as: distal extremity pain at rest that requires the subject to use analgesics for \>2 weeks; or peripheral ischemic ulcer(s); or areas of gangrene.
* The subject will have a TcPO2 of \</= 40 mmHg.
* Subjects will have one or both of the following hemodynamic indicators of severe peripheral arterial occlusive disease: (a) Ankle systolic pressure of \</= 70 mmHg; (b)Toe systolic pressure \</= 50 mmHg.
* The subject is a poor candidate for standard revascularization treatment options for peripheral arterial disease, based on inadequate bypass conduit, unfavorable anatomy, or poor operative risk.
* Subject has signed an informed consent form either directly or through a legally authorized representative
* If female, the subject must be (a) at least one year post-menopausal, or (b) surgically sterile, or (c) if the subject is of child-bearing potential, she must have been practicing contraception for at least 12 weeks prior to entering the study.
* If subject is of reproductive potential, he or she must be using an accepted and effective (barrier) form of birth control during the study.
* Subjects will be on a statin and an anti-platelet agent as part of their standard of care and must be stable on these regimens for at least 4 weeks prior to treatment.

Exclusion Criteria:

* Subjects, who in the opinion of the investigator, have a vascular disease prognosis that indicates they would require a major amputation (at or above the ankle) within 4 weeks of start of treatment.
* Subjects with a diagnosis of Buerger's disease (Thromboangitis Obliterans).
* Subjects with hemodynamically significant aorto-iliac occlusive disease.
* Subjects who have had a revascularization procedure within 12 weeks prior to treatment initiation that remains patent. Revascularization procedures that are evidenced to have failed for \>2 weeks prior to treatment initiation are acceptable.
* Subjects who require a change in their hypertension medication as part of their standard of care within 4 weeks prior to treatment.
* Evidence or history of malignant neoplasm (clinical, laboratory or imaging), except for basal cell carcinoma of the skin.
* Subjects who have proliferative diabetic retinopathy or severe, non-proliferative retinopathy
* Subjects with end stage renal disease (ESRD) defined as significant renal dysfunction evidenced by a creatinine of \> 2.5, or receiving chronic hemodialysis therapy.
* A subject who has hepatic cirrhosis, viral hepatitis, or is HIV positive.
* Subjects with a clinically significant liver enzyme abnormality (i.e., AST or ALT more than two times the upper limit of normal and/or bilirubin more than 50% the upper limit of normal).
* Subjects requiring the use of hyperbaric oxygen treatment for wound healing during the screening and 6 month follow-up period.

Answer: C