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:

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.
B: Inclusion Criteria:

* Males or females older than 18 years of age.
* Limb ischemia with ABI of \< 0.7 in the index lower extremity in two consecutive examinations done at least 1 week apart.
* Limb ischemia with resting ischemic pain and/or claudication at 100 meters and/or non-healing ulcers.
* Claudication
* Patients not considered candidates for surgical or percutaneous revascularization, due to poor target vessels, inability to cross total occlusions, or a morbidity which precludes general anesthesia.

Exclusion Criteria:

* Inability to provide informed consent.
* Previous angiogenic therapy.
* Known sensitivity to gentamycin and/or amphotericin B.
* Use or expected use of antineoplastic drugs.
* Any illness, which might affect the patient's survival after enrollment in the protocol.
* Any illness or significant laboratory abnormality, which in the investigator's judgment will interfere with the patient's ability to comply with the protocol, compromise the patient's safety, or interfere with the interpretation of the study results.
* No evidence of acute infection
* WBC \> 15000.
* WBC \< 4000.
* Serum Creatinine \> 3.0 mg/dL in patients who are not in hemodialysis.
* Pregnant women or women planning to become pregnant or unwilling to use appropriate birth control methods before and 2 months after cell infusion.
* Recent myocardial infarction within 3 months prior to screening.
C: 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.
D: Inclusion Criteria:

* Patients with unilateral critical chronic limb ischemia but not suitable candidates for non-surgical or surgical revascularization
* Before being included, the patient must be screened for human immunodeficiency virus, hepatitis B virus, hepatitis C virus, treponema pallidum

Exclusion Criteria:

* Buerger disease
* Ischemic ulcers with infectious symptoms
* Diabetes mellitus with HbA1c \> 7,5% or with proliferative retinopathy
* Past or current malignancy
* Contra-indication to general anaesthesia
* Chronic haemodialysis
* Prothrombin Time \< 60%,
* Recent onset (within 3 months) of myocardial infarction or brain infarction
* Coronary angioplasty within 1 year
* Atrial fibrillation, mechanical mitral prosthetic valve
* Unexplained hematological abnormality.
* Expected life span less than six months
* Patient not competent to give informed consent

Answer: A