Please select the eligibility criteria that correspond to the clinical trial below.
Title: Double-blind, Randomized, Placebo-controlled, Parallel Group and Dose-finding, Multicentric, Safety and Efficacy Study With Intramuscular Injections of NV1FGF in Subjects With Intermittent Claudication
Brief Summary: The primary objective is to assess safety and efficacy of two different doses of NV1FGF as compared to placebo.

The secondary objective is to assess the pharmacokinetics of NV1FGF and FGF-1 protein.


Options:
A: Inclusion criteria:

* Severe PAOD defined as Rutherford's Grade II, category 4 or Grade III, category 5 and 6
* Pain at rest for at least 2 weeks duration and/or trophic lesions for at least the previous 14 days with no signs of healing (no reduction in ulcer size or depth)
* Objective evidence of peripheral vascular disease (resting Ankle Brachial Index \< 0.4 and/or resting Toe Brachial Index \< 0.3 and/or metatarsal Peripheral Vascular Resistance flat or barely pulsatile in the diseased limb on 2 consecutive examinations performed at least 2 weeks apart)
* Angiographic demonstration of total occlusion of the affected limb of one or more of the iliac, superficial femoral, popliteal and/or one or more infrapopliteal arteries
* Poor candidate for surgical intervention or revascularization procedures (no tibial artery incontinuity as defined from mid-leg distance from the foot and no autologous tissue available)

Exclusion criteria :

* Previous or current history of malignant disease. Patients who had successful tumor resection more than 10 years prior to inclusion into the study and had no recurrence and patients who had curatively resected basal/squamous cancer of the skin were allowed for inclusion
* Abnormal chest X-ray with suspected malignant tumor presence
* Positive stool hemoccult (expect if due to hemorrhoids)
* Positive Prostate Specific Antigen for men with suspected malignant tumor presence
* Abnormal mammography for women with suspected malignant tumor presence
* Papanicolaou smear (for women) of Class IV or Class V characterization
* Proliferative retinopathy

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

* Age\>40 years
* History of typical intermittent claudication lasting for at least 3 months, showing no improvement and consistent with treadmill test findings
* Objective evidence of Peripheral Arterial Occlusive Disease. After 10 minutes of rest, either by Ankle brachial index measure (ABI) \<0.8 or Systolic ankle pressure (AP) \< 50 mmHg or Systolic toe pressure \<50 mmHg
* Patent femoral inflow above the level of injections recently (\<2 weeks) documented either with Doppler ultrasonography or Magnetic Resonance Angiography or Angiography

Exclusion criteria:

* Evidence of other causes for leg pain other than intermittent claudication.
* Illnesses limiting subject exercise capacity (angina pectoris, heart failure, respiratory disease, orthopaedic disease, neurological disorders...)
* Pain at rest
* Buerger's disease
* Positive serology for HIV 1 or 2, positive serology hepatitis B or C.
* Subjects with serum creatinine \> 2 mg/dl (176 µmol/l) and subjects on dialysis.
* Active proliferative retinopathy defined by the presence of new vessel formation and scarring.
* Subjects who had a stroke or neurologic deficit presumed to be due to stroke within 3 months prior to the first administration of study treatment
* Previous treatment with any angiogenic growth factor
* Pregnant or breast feeding women or who disagree to practice a medically accepted method of birth control. Men and women who do not agree to use condoms as the only accepted protection barrier, for the entire study period
* Serious concomitant medical conditions not adequately controlled.
* Current alcohol or drug abuse

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:

1. Participants with an ankle brachial index (ABI) ≤ 0.90 will be eligible for participation.
2. Participants with an ABI \> 0.90 but ≤ 1.00 who experience a 20% drop in ankle pressure after the heel-rise exercise will be eligible.
3. Participants with an ABI \> 0.90 who have medical record evidence of prior lower extremity revascularization and experience a 20% drop in ankle pressure after the heel-rise exercise will be eligible for inclusion.
4. Participants with an ABI \> 0.90 who have medical record evidence of a non-invasive vascular laboratory test result consistent with PAD. Note that a screen-positive test from Lifeline Screening is not sufficient for inclusion in the study.

Exclusion Criteria:

The following exclusion criteria will be initially assessed by telephone:

1. Below or above-knee amputation.
2. Wheelchair confinement.
3. Use of a walking aid other than a cane (i.e. people using walkers).
4. Non-English speaking.
5. Significant hearing impairment.
6. Significant visual impairment.
7. Diagnosis of Parkinson's disease.
8. Inability to return to the medical center at the required visit frequency (three times per week).
9. \> Class II New York Heart Association heart failure or angina (symptoms at rest or with minimal exertion).
10. Any increase in angina pectoris symptoms during the previous 6 months or angina at rest.
11. Foot ulcer. (Participants with a foot ulcer will be excluded by telephone and/or during a baseline study visit).
12. Lower extremity revascularization in the last three months or major orthopedic surgery during the previous three months.
13. Myocardial infarction, stroke, or coronary artery bypass grafting during the previous 3 months.
14. Major medical illnesses including end stage renal disease requiring dialysis and chronic lung disease requiring oxygen, since these individuals may not be able to adhere to study requirements. Participants who only use oxygen at night may still qualify.
15. Potential participants who have received G-CSF, GM-CSF, or erythropoietin within the past year will be excluded because these interventions may influence study outcomes independently of the interventions.
16. Pre-menopausal women will be excluded because cyclic estrogen changes can influence progenitor cell levels.
17. Potential participants with diabetes and documented proliferative retinopathy will be excluded because GM-CSF may exacerbate this condition.
18. Potential participants with a history of myeloid malignancy will be excluded because GM-CSF may exacerbate these conditions.
19. Potential participants who have been treated for late stage cancer during the past three years, since GM-CSF may theoretically activate quiescent cancer cells.
20. Planned lower extremity revascularization within the next 6 months.
21. Current participation in another clinical trial. If a participant recently completed a clinical trial, at least three months must have passed before they can be considered for the PROPEL Trial. However, for a clinical trial of stem cell or gene therapy intervention, potential participants will be potentially eligible immediately after the final study visit of the stem cell or gene therapy clinical trial, so long as at least six months has passed since the participant received their final treatment in the stem cell or gene therapy intervention.
22. Walking for exercise at a level comparable to that targeted in our intervention.
23. Current participation in or completion of a cardiac rehabilitation program within the last six months.

    The following exclusion criteria will be assessed at the time of the study visit or later:
24. Severe aortic stenosis identified by physical exam at the study visit.
25. Critical limb ischemia identified by physical exam at the study visit.
26. Coronary ischemia during exercise, defined as ST segment depression \> 1 mm during the baseline exercise treadmill test, with or without associated chest discomfort, without a perfusion stress test demonstrating no reversible ischemia within the previous 3 months.
27. Left-bundle branch block or significant ST-T wave changes on the baseline ECG without a perfusion stress test demonstrating no reversible ischemia within the previous 3 months.
28. Stopping during the treadmill stress test for shortness of breath, chest pain, hip pain, knee pain, or another symptom that may not represent ischemic leg pain.
29. Stopping during the six-minute walk test for symptoms other than ischemic leg symptoms.
30. Foot ulcer identified at the study visit.
31. Mini-Mental Status Examination (MMSE) score \< 23 or disabling psychiatric disease.
32. Failure to complete a study run-in period.
33. Walking impairment due to a cause other than PAD.

In addition to the exclusion criteria listed above, individuals thought to be poorly suited to the intervention (i.e. not a good fit) can be excluded at the discretion of the principal investigator.

Answer: B