Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized Double-Blind Placebo-Controlled Parallel Group Study of the Efficacy and Safety of XRP0038/NV1FGF on Amputation or Any Death in Critical Limb Ischemia Patients With Skin Lesions
Brief Summary: Primary objective is to demonstrate the superiority of riferminogene pecaplasmid (XRP0038/NV1FGF) over placebo in the prevention of major amputation above the ankle of the treated leg or of death from any cause, whichever comes first, in critical limb ischemia (CLI) patients with skin lesions.

Secondary objectives are to evaluate:

* The efficacy of riferminogene pecaplasmid versus placebo for delaying the time to major amputation;
* The efficacy of riferminogene pecaplasmid versus placebo for delaying the time to death;
* The safety of riferminogene pecaplasmid in the study population.


Options:
A: Inclusion Criteria:

* Male or female person aged 40 or older
* Subject with diagnosed lower limb ischemia (Fontaine-Pokrovsky Stages IIa-III of chronic limb ischemia)
* Signed informed consent

Exclusion Criteria:

* Any disease that can, in the opinion of the treating physician, affect the outcome of the study
* Patients with addictive disorders or substance abuse
* Pregnancy or nursing
* All other exclusion criteria listed in the summary of product characteristics (SmPC)
B: Inclusion Criteria:

* Subjects with prior decision for amputation above the ankle because of severe PAOD
* Males or females above 18 years
* Females must be either:

  * Non pregnant, non lactating , having practicing a medically accepted method of birth control for more than 2 months prior screening visit;
  * or surgically sterilized (tubal ligation or hysterectomy)
  * or post menopausal for at least one year

Exclusion Criteria:

* Subjects with urgent need for amputation that cannot await until completion of the screening period (up to 4 weeks), added to the minimum required 48 hours between study test medication administration and tissue sample collection
* Previous or current history of malignant disease (subjects with successful tumor resection more than 5 years -without any recurrence- prior to study start could be enrolled)
* Abnormal Chest X-ray or mammography with suspicion of malignant disease
* Positive stool hemoccult (except in case of hemorrhoids or any other identified cause with no malignancy origin)
* Men with positive Prostate Specific Antigen (PSA) (above 2.5 ng/ml in subjects \< 50 years and above 5 ng/ml in subjects above 50 years)
* Females with Papanicolaou smear of Class IV or Class V characterization
* Serious concomitant medical conditions not adequately controlled
* Alcohol or drug abuse
* Active proliferate retinopathy defined by the presence of new vessel formation and scarring
* Participation in clinical trials of non-approved experimental agents within four weeks before study entry;
* Positive serology for HIV1 or 2
* Creatinine above 2.0 mg/dl (176 µmol/l), unless the subject is on hemodialysis / peritoneal dialysis and diagnosed with complete and irreversible renal failure or end-stage renal disease (ESRD)
* Subjects who had a stroke or a neurological deficit presumably due to a stroke, within 3 months prior to study treatment (Amendment #1)
* Alpha-fetoprotein (AFP) in serum \> 15 µg/l, unless liver ultrasound ruled out any malignant disease
* Positive serology for hepatitis B or C, unless liver ultrasound ruled out any malignant disease.

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