Hemodynamic Effects of Intramuscular PDA-002 in Subjects Who Have Diabetic Foot Ulcer With Peripheral Arterial Disease

A Phase 2 Double-blind, Placebo-controlled Study to Evaluate Hemodynamic Effects of Intramuscular Injection of Human Placenta-derived Cells (Pda-002) in Subjects Who Have Diabetic Foot Ulcer With Peripheral Arterial Disease

Study PDA-002-DFU-003 is a Phase 2, multicenter, randomized, double blind, placebo-controlled, dose range finding study in subjects who have diabetic foot ulcer (DFU) with peripheral arterial disease (PAD). The study will enroll approximately 24 subjects. This study will investigate the hemodynamic effects, clinical efficacy, and safety of 3 monthly intramuscular (IM) injections of PDA-002 in subjects who have DFU with PAD.

Although the study protocol was developed, the study was withdrawn prior to enrollment. Four subjects were screened but did not meet eligibility criteria, and no participants were enrolled.

Inclusion Criteria:

1. Males and females, at least 18 years of age or older at the time of signing the informed consent document.

2. Diabetes mellitus Type 1 or Type 2.

3. Diabetic foot ulcer with severity of Grade 1 (full thickness only) or Grade 2 on the Wagner Grading Scale of greater than one month duration which has not adequately responded to conventional ulcer therapy.

4. Subjects who meet one or more of the following criteria of arterial insufficiency in the foot with the index ulcer:

   1. Peripheral arterial disease with ABI ≥ 0.40 and ≤ 0.80 or TBI ≥0.30 and ≤ 0.65.
   2. Transcutaneous oxygen measurement between 20 to 40 mmHg.

5. No planned revascularization or amputation over the next 3 months after screening visit, in the opinion of the investigator.

6. Dosing should not begin until at least 14 days after a failed reperfusion intervention and at least 30 days after a successful reperfusion intervention

Exclusion Criteria:

1. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study, at the discretion of the investigator.
2. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he or she were to participate in the study, at the discretion of the investigator.
3. Pregnant or lactating females.
4. Subjects with a body mass index > 40 mg/m2 at Screening.
5. Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 at Screening calculated using the Modification of Diet in Renal Disease Study equation or history of eGFR decline > 15 mL/min/1.73 m2 in the past year.
6. Untreated chronic infection or treatment of any infection with systemic antibiotics,including the ulcer site. Subject must be antibiotic free within 1 week prior to dosing with Investigational Product (IP).
7. Known osteomyelitis or infection or cellulitis at or adjacent to the index ulcer.
8. Limb pain at rest due to limb ischemia.
9. Uncontrolled hypertension (defined as diastolic blood pressure > 100 mmHg or systolic blood pressure > 180 mmHg during Screening at 2 independent measurements taken while subject is sitting and resting for at least 5 minutes).
10. Poorly controlled diabetes mellitus (hemoglobin A1c >12% or a screening serum glucose of ≥ 300 mg/dL).
11. Untreated proliferative retinopathy.
12. History of malignant ventricular arrhythmia, Canadian Cardiovascular Society (CCS) Class III-IV angina pectoris, myocardial infarction/PCI (percutaneous coronary intervention)/CABG (coronary artery bypass graft) in the preceding 6 months prior to signing the Informed Consent (ICF),pending coronary revascularization in the following 3 months, transient ischemic attack/cerebrovascular accident in the preceding 6 months, prior to signing the ICF and/or New York Heart Association [NYHA] Stage III or IV congestive heart failure.
13. Abnormal ECG: new right bundle branch block (BBB) ≥ 120 msec in the preceding 3 months prior to signing the ICF.
14. Uncontrolled hypercoagulation syndrome.
15. Life expectancy less than 2 years due to concomitant illnesses.
16. In the opinion of the investigator, the subject is unsuitable for cellular therapy.
17. History of malignancy within 5 years prior to signing the ICF except basal cell or squamous cell carcinoma of the skin or remote history of cancer now considered cured or positive Pap smear with subsequent negative follow-up.
18. History of hypersensitivity to any of the components of the product formulation (including bovine or porcine products, dextran 40, and dimethyl sulfoxide [DMSO]).
19. Subject has received an investigational agent -an agent or device not approved by the US Food and Drug Administration (FDA) for marketed use in any indication- within 90 days (or 5 half-lives, whichever is longer) prior to treatment with study therapy or planned participation in another therapeutic study prior to the completion of this study.
20. Subject has received previous investigational gene or cell therapy.