E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Intermittent Claudication (IC); Fontaine class IIb; Rutherford category 2-3 |
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E.1.1.1 | Medical condition in easily understood language |
Intermittent Claudication (IC) (Peripheral arterial occlusive disease); Fontaine class IIb; Rutherford category 2-3 |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10022562 |
E.1.2 | Term | Intermittent claudication |
E.1.2 | System Organ Class | 10047065 - Vascular disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The objective of the study is to further establish the safety profile of local PLX-PAD injections and to evaluate the clinical efficacy of PLX-PAD in IC subjects. |
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E.2.2 | Secondary objectives of the trial |
The objective of the study is to further establish the safety profile of local PLX-PAD injections and to evaluate the clinical efficacy of PLX-PAD in IC subjects. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Adult male or female subjects between 45 to 85 years of age (inclusive) at the time of screening visit. 2. 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 3. 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) 4. Evidence of significant (>50%) stenosis infra-inguinal occlusive disease (distal to the common femoral artery) as confirmed by documented results from Duplex, MRA, CTA and/or contrast angiogram completed within 3 months prior to screening 5. 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). 6. 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 a vasodilatator prescribed for IC (including Cilostazol, Pentoxifylline, Naftidrofuryl, and prostanoids) if indicated. For Subjects that were previously receiving a vasodilatator, they should be washed out for at least 2 weeks prior to the first ETT. 7. 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. 8. Signed written informed consent. |
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E.4 | Principal exclusion criteria |
1. Ischemic rest pain; ulceration or gangrene (Fontaine class III-IV; Rutherford category 4-6). 2. Failed lower extremity arterial reconstruction (surgical or endovascular) or sympathectomy within the prior one month of screening. 3. Planned revascularization (surgical or endovascular intervention) within 12 months after screening. 4. Lower extremity arteries inflow obstruction (defined as a greater than 50% stenosis of aorta, iliac and/or common femoral arteries) 5. History of Buerger’s disease. 6. Uncontrolled hypertension (defined as diastolic blood pressure > 100 mmHg or systolic blood pressure >180mmHg during screening). 7. Uncontrolled diabetes defined as glucose control HbA1c > 8% (64mmol/mol) at screening. 8. Life-threatening ventricular arrhythmia - except in subjects with an implantable cardiac-defibrillator. 9. Serum Creatinine level>2.5mg/dl. 10. SGPT (ALT), SGOT (AST) >2.5 x upper limit of normal. 11. Hemoglobin < 10 g/dl. 12. 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. 13. Transient Ischemic Attack (TIA)/Stroke within 3 months prior to screening. 14. Subjects with severe congestive heart failure symptoms (i.e. NYHA Stage III to IV). 15. Subjects with Implant of mechanical prosthetic heart valve(s). 16. Pulmomary disease requiring supplemental oxygen treatment on a daily basis. 17. Active significant infection including but not limited to osteomyelitis, fasciitis, or severe/purulent cellulitis. 18. History of malignancy within 5 years prior to screening including basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) of the treated leg (a subject with BCC or SCC of the opposite leg can be included). 19. 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. 20.Subjects who are on oral anticoagulant therapy. Unless, upon primary care physician and/or Investigator’s discretion treatment can be safely interrupted/discontinued around each IP injection to reduce risk of hemorrhage 21. Immunocompromised subjects for any reason, at screening. 22. Known allergies to any of the following: dimethyl sulfoxide (DMSO), human serum albumin, bovine serum, or recombinant trypsin used in the cell production process. 23. Known sensitivity to Gentamycin. 24. Known sentitivity to antihistamine drugs. 25. History of allergic/hypersensitivity reaction to any substance having required hospitalization and/or treatment with intra-venous steroids/epinephrine or in the opinion of the investigator the patient is at high risk of developing severe allergic/hypersensitivity reactions. 26. History of acute transfusion reaction or history of autologous/allogeneic bone marrow or solid organ transplantation. 27. History of uncontrolled Asthma (GINA III-IV) or chronic urticarial. 28. Medical history of Human Immunodeficiency Virus (HIV) or syphilis positivity at time of screening. 29. Known active Hepatitis B, or Hepatitis C infection at the time of screening. 30. 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). 31. In the opinion of the Investigator, the subject is unsuitable for participating in the study. 32. 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). 33. Subjects that have prior exposure to gene or cell based therapy. 34. Subjects who are legally detained in an official institute. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Log ratio of week 52 maximal walking distance to baseline maximal walking distance |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Safety Endpoints: The evaluation of the these endpoints will be done every visit.
Primary Efficacy Endpoint: Will be assessed at week 52 |
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E.5.2 | Secondary end point(s) |
• Revascularization rates • Log ratio of week 52 and 65 of Initial Claudication Distance (ICD) to baseline ICD • Change from baseline in MWD and ICD at the intermediate time points of week 12, 3952 and 65 • Change from baseline in health-related Quality of Life Questionnaires • Change from baseline in PAD Questionnaire (PAQ) • Change from baseline in Quality of Life (QoL) Questionnaire (SF-36v2) • Change from baseline in hemodynamic measurements (resting ABIand/or TBI)
Safety Endpoints: • Treatment emergent Adverse events, SAEs, AEs leading to premature study termination • Safety laboratory values • Immunological reaction • Major Amputation of the Lower Extremity • Death rates |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The evaluation of the these endpoints will be done every visit. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Israel |
Korea, Republic of |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |