FGF-1 for Intramuscular Injection for the Treatment of Peripheral Arterial Disease

Study Overview
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Brief Summary
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FGF-1 for the treatment of patients with peripheral arterial disease with intermittent claudication.

Detailed Description
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FGF-1 administered by intramuscular injection for the treatment of peripheral arterial disease with intermittent claudication. Eligible patients are allocated to one of three treatment arms. Patients within each dosing group will be randomized between study drug and vehicle control. Safety, pharmacokinetics, and cardiovascular improvement will be evaluated at day 1 and weeks 1, 4 and 12 post dosing.

Official Title
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A Phase 1, Open Label, Dose Response, Pilot Study to Evaluate the Safety and Tolerability of Human Fibroblast Growth Factor-1 (FGF-1) in Peripheral Arterial Disease Patients With Intermittent Claudication

Conditions
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Peripheral Arterial Disease, Stenosis, Intermittent Claudication

Intervention / Treatment
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* Drug: FGF-1
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Subjects considered eligible to enter the study must sign an informed consent form prior to the initiation of any study procedures. In the event that the subject must be withdrawn and is re-screened for study participation at a later date, a new informed consent form must be signed. Subjects must be competent to give written informed consent. Age must be ≥50 and ≤75 years of age with a life expectancy of > 1 year and leg survival > 6 months. Patients >75 and ≤80 years of age will be considered if they show no signs of cognitive or muscle function decline and are fully able to comply with the protocol. Patients must have experienced intermittent claudication for at least 6 months and have been stable for the past 3 months. Patients must have peripheral arterial disease, as confirmed by a resting ABI ≥0.40 and <0.90 based on at least one leg as measured using both the dorsal pedis and posterior tibial arteries. Stenosis of >70% up to total occlusion must be present in the popliteal artery and/or in the tibial peroneal trunk or at least 2 tibial arteries above the ankle without inflow limitation of the popliteal artery. Adequate popliteal inflow is defined as continuous flow from the abdominal aorta, iliac, common femoral and superficial femoral with any stenosis < 50% as determined either by intra-arterial DSA, CTA or Gd CE-MRA. The screening Gardner treadmill test peak walking times (PWT) must be >1 minute and < 12 minutes and limited by pain in one or both calves. Preexisting medication regime must be stable for 6 weeks preceding dosing. Exclusion Criteria Evidence of critical leg ischemia, i.e. ischemic rest pain or ischemic ulceration Treadmill walking limited by conditions other than intermittent claudication including arthritis, angina and dyspnea Lower limb amputation of, or in, either leg including toes Evidence of limb ischemia from immunologic or inflammatory disorders Leg surgery or revascularization within past 6 months or peripheral angioplasty within past 3 months or anticipated during study Participation in any investigational device or drug trial within the past 6 months Myocardial infarction, unstable angina, stroke or ischemic attack within past 6 months New York Heart Association (NYHA) class II, III or IV heart failure, restrictive or hypertrophic cardiomyopathy or severe valvular disease QTc elongation greater than 450 ms in males or 460 ms in females PT (INR), PTT, urinalysis, thyroid function (T3, T4, TSH) outside normal limits Hemorrhage or thrombotic events (e.g. deep vein thrombosis) within past 6 months Thrombocytopenia (<100,000/µl), history of heparin-induced thrombocytopenia Major surgery with the past 6 months Positive proliferative retinopathy exam Present of any type of cancer or history of cancer except past (but not present) basal cell dermal carcinoma not on either leg Inflammatory or progressive fibrotic or myelofibrotic disorders Patients experiencing bacterial or viral infection (e.g. hepatitis or HIV) or who may otherwise be febrile Hemoglobin A1c(HgbA1c) of >8% Type I diabetes Total fasting cholesterol >200 Uncontrolled hypertension (≥160 systolic or ≥100 diastolic pressure) or hypotension (<90 systolic or <60 diastolic pressure) Disease or drug (e.g. systemic corticosteroid) immuno-compromised Hepatic dysfunction as defined either by AST or ALT > 2.0 times the upper limit of normal Serum creatinine of ≥ 2.5 mg/dl Proteinuria (urine protein/creatinine ratio > 3) Antiproliferative drugs (e.g. thalidomide, hydroxyurea) Radiation therapy Implanted devices not compatible with strong magnetic fields Life expectance of less than 1 year Females who are premenopausal and not sterilized or using adequate birth control or are either pregnant, intend to become pregnant or are nursing

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>The dosing groups correspond to total doses of 0 µg/kg of FGF-1. | Drug: Placebo<br>* Vehicle: 0 µg/kg<br>|
| Active Comparator: Human FGF-1<br>The dosing groups correspond to total doses of either 3, 10 or 30 µg/kg of FGF-1. | Drug: FGF-1<br>* Doses of FGF-1: 3 ug/kg; 10 ug/kg; 30 ug/kg Low dose: 3.0 μg/kg Mid dose: 10 μg/kg High dose: 30 µg/kg<br>* Other names: Acidic FGF;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events as a measure of safety and tolerability of i.m. injected Cardio Vascu Grow TM, a recombinant Human Fibroblast Growth Factor-1 (FGF-1-141) | Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) | From enrollment through study completion, an average of 12 weeks | 
| Change from baseline in safety laboratory measurements at 12 weeks | Safety laboratory evaluations on hematology, serum chemistry, and urinalysis | From enrollment through study completion, an average of 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma FGF-1 (1-141) pharmacokinetic measurements at pre-dose, 5, 15, and 30 minutes and at 1, 2, 4, 6, 10, and 24 hours | Pharmacokinetic plasma concentrations of FGF-1 (1-141) | From enrollment through study completion, an average of 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Peripheral Arterial Disease, Ischemia, Intermittent Claudication