Intermittent Claudication, Peripheral Artery Disease
Conditions
Brief summary
The objective of the study is to establish the safety profile of Intramuscular PLX-PAD injections and to evaluate the clinical efficacy of it in IC subjects comprising of 4 treatment groups: 1. Double treatment of PLX-PAD low dose 2. Double treatment of PLX-PAD high dose 3. Double treatment of Placebo 4. Single treatment of PLX-PAD high dose and additional treatment of Placebo. Subjects will receive the assigned treatment twice to the affected leg, within 12-weeks interval between each treatment. The study will be comprised of 5 stages: Screening period of up to 4 weeks,first treatment of PLX-PAD or placebo followed by additional injection after 12 weeks and with follow-up of 12 months post second injection
Interventions
BIOLOGICALPLX-PAD Low dose
BIOLOGICALPLX-PAD high doses
BIOLOGICALDouble Placebo
BIOLOGICALhigh dose +Placebo
Sponsors
Pluristem Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
45 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Adult male or female subjects between 45 to 85 years of age (inclusive) at the time of screening visit. * Subjects with a diagnosis of peripheral artery disease, secondary to atherosclerosis, confirmed by one of the following criteria assessed at the screening visit: * Resting ankle-brachial index (ABI) ≤ 0.80 or * Resting ABI ≤ 0.90 and \>20% decrease in ABI from rest to exercise when measured within 1 minute after treadmill exercise or * Toe-brachial index (TBI) ≤ 0.60 * Lifestyle-limiting, moderate to severe claudication (symptoms present and stable for \> 6 months and not significantly changed within the past 3 months prior to screening). * Evidence of significant (\>50%) stenosis infra-inguinal occlusive disease as confirmed by documented results from Duplex, MRA, CTA and/or contrast angiogram completed within 3 months prior to screening. * The longest maximal walking distance (MWD) from the Screening Period exercise treadmill tests (ETT), utilizing a modified Gardner Protocol (Appendix I), must be between 1 and 10 minutes (inclusive). * Subjects who have persistent claudication symptoms despite having been recommended an exercise program if feasible, and or despite having been on a stable dose of Cilostazol, if indicated. Subjects should be Cilostazol free for at least 2 weeks prior to the first ETT. * Subjects should be receiving standard of care drugs for vascular disease including anti-platelet agent(s) and statin medication, as well as anti-hypertensive medication(s) and oral hypoglycemic agents/insulin, if indicated. * Signed written informed consent.
Exclusion criteria
* Ischemic rest pain; ulceration or gangrene (Fontaine class III-IV; Rutherford category 4-6). * Failed lower extremity arterial reconstruction (surgical or endovascular) or sympathectomy within the prior one month of screening. * Planned revascularization (surgical or endovascular intervention) within 12 months after screening. * Lower extremity arteries inflow obstruction (defined as a greater than 50% stenosis of aorta, iliac and/or common femoral arteries). * History of Buerger's disease. * Uncontrolled hypertension (defined as diastolic blood pressure \> 100 mmHg or systolic blood pressure \> 180 mmHg during screening). * Uncontrolled diabetes defined as glucose control HbA1c \> 9% at screening. * Life-threatening ventricular arrhythmia - except in subjects with an implantable cardiac-defibrillator. * Serum Creatinine level\>2.5mg/dl. * SGPT (ALT), SGOT (AST) \>2.5 x upper limit of normal range. * Hemoglobin \< 10 g/dl. * Unstable cardiovascular disease defined as myocardial infarction (STEMI or NSTEMI) within 3 months prior to screening, or unstable angina - characterized by increasingly frequent episodes with modest exertion or at rest, worsening severity, and prolonged episodes. * Transient Ischemic Attack (TIA)/Stroke within 3 months prior to screening. * Subjects with severe congestive heart failure symptoms (i.e. NYHA Stage III to IV). * Subjects with Implant of mechanical prosthetic heart valve(s). * Pulmonary disease requiring supplemental oxygen treatment on a daily basis. * Severe, active infection of the involved extremity(ies), including osteomyelitis, fasciitis, or severe/purulent cellulitis. * History of malignancy within 5 years prior screening requiring chemotherapy and/or radiotherapy and/or immunotherapy, excluding basal or squamous cell carcinoma of the skin. * Exercise is limited by any condition other than IC, including but not limited to congestive heart failure, chronic pulmonary disease, angina pectoris, or degenerative joint disease. * Uninterrupted use of warfarin or non-steroidal anti-inflammatory agents (with the exception of ibuprofen at doses up to 1,200 mg/day or Diclofenac at dose of 75mg/day). * Subjects who are on oral anticoagulant therapy (warfarin, dabigatran, apixaban, endoxaban and rivaroxaban). Unless, upon primary care physician and/or Investigator's discretion the subjects who are on warfarin treatment can switch to Low Molecular Weight Heparin treatment (such as: Clexane) 5-7 days prior study treatment administration and return to warfarin treatment 24 hours post study treatment administration. * Subjects who are taking immunosuppressive treatment (including high dose steroids). * Known allergies to protein products (Bovine serum, or recombinant trypsin) used in the cell production process. * Known sensitivity to Gentamycin. * Known sensitivity to antihistamine drugs. * History of hospitalization due to allergic/hypersensitivity reaction to any substance (e.g. Food or drug). * Medical history of Human Immunodeficiency Virus (HIV) or syphilis positivity at time of screening. * Known active Hepatitis B, or Hepatitis C infection at the time of screening. * Pregnant or breast-feeding women or women of childbearing age not protected by an effective contraceptive method of birth control (such as double barrier, oral or parenteral hormonal, intrauterine device and spermicide). * In the opinion of the Investigator, the subject is unsuitable for participating in the study. * Subject is currently enrolled in, or has not yet completed a period of at least 30 days since ending other investigational device or drug trial(s). * Subjects that have prior exposure to gene or cell based therapy. * Subjects who are legally detained in an official institute.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Log ratio of week 52 maximal walking distance(MWD)to baseline MWD | 12 months |
Countries
Germany, Israel, South Korea, United States
Outcome results
None listed