Efficacy and Safety of Intramuscular PDA-002 in Subjects Who Have Diabetic Foot Ulcer With and Without Peripheral Arterial Disease


Trial ID: NCT02264288


The PDA-002-DFU-002 trial is a Phase 2, multicenter, randomized, double blind, placebo controlled, dose range finding study. The study will enroll approximately 133 subjects in four treatment groups. The primary objective of the study is to assess the efficacy and safety of PDA-002 administered intramuscular (IM) in subjects who have DFU with and without PAD. The secondary objective is to explore potential clinical efficacy by assessing changes in vascular parameters such as Ankle-Brachial Index and Toe-Brachial Index (ABI and/or TBI), Transcutaneous oxygen measurements (TcPO2).

Official Title

A Phase 2 Multicenter, Randomized, Doubleblind, Placebo-Controlled, Dose Range Finding Study to Evaluate the Efficacy and Safety of Intramuscular Injection of Human Placenta-derived Cells (Pda-002) in Subjects Who Have Diabetic Foot Ulcer With Peripheral Arterial Disease

Stanford Investigator(s)


Inclusion Criteria:

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

   2. Understand and voluntarily sign an informed consent document prior to any study
   related assessments/procedures are conducted.

   3. Able to adhere to the study visit schedule and other protocol requirements.

   4. Diabetes mellitus Type 1 or Type 2.

   5. Diabetic foot ulcer with severity of Grade 1 (full thickness only) or Grade 2 on the
   Wagner Grading Scale (Appendix A) of greater than one month duration which has not
   adequately responded to conventional ulcer therapy with a size of at least of 1cm2
   except if present on the toe. The maximum lesion size range in the index ulcer is ≤
   10cm2. The measurement of the index ulcer is to be evaluated and measured after
   debridement (if necessary) at the Screening Visit. If located on the plantar aspect of
   the foot, the index ulcer must be able to be adequately offloaded in the assessment of
   the investigator.

   6. No planned revascularization or amputation over the next 3 months after Screening
   visit, in the opinion of the Investigator.

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

   8. Subjects should be receiving appropriate medical therapy for hypertension and diabetes
   any other chronic medical conditions for which they require ongoing care.

   9. A female of childbearing potential must have a negative serum pregnancy test at
   Screening and a negative urine pregnancy test prior to treatment with study therapy.
   In addition, sexually active FCBP must agree to use 2 of the following adequate forms
   of contraception methods simultaneously such as: oral, injectable, or implantable
   hormonal contraception; tubal ligation; IUD; barrier contraceptive with spermicide or
   vasectomized partner for the duration of the study and the Follow-up Period.

10. Males (including those who have had a vasectomy) must agree to use barrier
   contraception (latex condoms) when engaging in reproductive sexual activity with FCBP
   for the duration of the study and the Follow-up Period.

Exclusion Criteria:

   1. Any significant medical condition, laboratory abnormality, or psychiatric illness that
   would prevent the subject from participating in the study.

   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.

   3. Any condition that confounds the ability to interpret data from the study.

   4. Pregnant or lactating females.

   5. Subjects with a body mass index > 45 kg/m2 at Screening.

   6. AST (SGOT) or ALT (SGPT) > 2.5 x the upper limit of normal (ULN) at Screening.

   7. Patient on renal dialysis for abnormal kidney function.

   8. An ABI < 0.4 and or TBI < 0.3 in the leg with the index ulcer.

   9. Bilirubin level > 2 mg/dL (unless subject has known Gilbert's disease) at Screening.

10. Untreated chronic infection or treatment of any infection with systemic antibiotics,
   including the ulcer site, must be free of antibiotics within 1 week prior to dosing
   with IP.

11. Active osteomyelitis, infection, or cellulites at or adjacent to the index ulcer.
   Patients with a history of being treated for an osteomyelitis without a surgical

12. Index ulcer that has decreased or increased in size by ≥ 30% during the
   Screening/Run-In/ Pre-Treatment Period.

13. Active Charcot Neuroarthropathy in the foot with the index ulcer

14. Pain at rest due to limb ischemia.

15. 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).

16. Poorly controlled diabetes mellitus (hemoglobin A1c > 12% or a screening serum glucose
   of ≥ 300mg/dl).

17. Untreated proliferative retinopathy.

18. History of malignant ventricular arrhythmia, CCS Class III-IV angina pectoris,
   myocardial infarction/ percutaneous coronary intervention (PCI) / coronary artery
   bypass graft (CABG) in the preceding 6 months prior to signing the informed consent
   form (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

19. Abnormal ECG: new right bundle branch block (BBB) ≥ 120 msec in the preceding 3 months
   prior to signing the ICF.

20. Uncontrolled hypercoagulation syndrome.

21. Life expectancy less than at 2 years at the time of signing the ICF due to concomitant

22. In the opinion of the Investigator, the subject is unsuitable for cellular therapy.

23. 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.

24. History of hypersensitivity to any of the components of the product formulation
   (including bovine or porcine products, dextran 40, and dimethyl sulfoxide [DMSO]).

25. 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

26. Subject has received previous investigational gene or cell therapy.


biological: 3 x 10^6 cells

biological: 10 x 10^6 cells

biological: 30 x 10^6 cells

other: Placebo


Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305