Study of PDA-002 in Subjects With Peripheral Arterial Disease and Diabetic Foot Ulcers

A Phase 1 Multicenter, Open-Label, Dose-Escalation Study to Evaluate the Safety and Efficacy of Intramuscular Injection of Human Placenta-Derived Cells (PDA-002) in Subjects With Peripheral Arterial Disease and Diabetic Foot Ulcers

This Phase 1, multicenter, open-label, dose-escalation study evaluated the safety and tolerability of intramuscular administration of PDA-002 (human placenta-derived cells) in subjects with peripheral arterial disease (PAD) and diabetic foot ulcers (DFU).

Study Overview

• Status: Completed
• Conditions: Peripheral Arterial Disease; Diabetic Foot Ulcer
• Intervention / Treatment: Biological: PDA-002

Detailed Description

The purpose of this Phase 1 study was to evaluate the safety, tolerability, and maximum tolerated dose (MTD) of PDA-002, a human placenta-derived cell therapy, administered by intramuscular injection in subjects with peripheral arterial disease (PAD) and diabetic foot ulcers (DFU). This was a multicenter, open-label, 3+3 dose-escalation study. Subjects received PDA-002 administered intramuscularly on Study Days 1 and 8 at 1 of 4 planned dose levels ranging from 3 × 10^6 to 100 × 10^6 cells. Dose escalation proceeded after review of safety data from previously enrolled subjects. Subjects were followed for safety assessments for up to 24 months.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85012
      • Carl T. Hayden Veterans Affairs Medical Center
  • California
    • Los Angeles, California, United States, 90095
      • UCLA
    • Palo Alto, California, United States, 94304
      • VA Palo Alto health
  • Illinois
    • North Chicago, Illinois, United States, 60064
      • Dr. Wiliam M. Scholl College of Podiatric Medicine
    • Springfield, Illinois, United States, 62702
      • Southern Illinois University School of Medicine
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Vascular Surgeon
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina School of Medicine
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Texas
    • McAllen, Texas, United States, 78501-2930
      • Complete Family Foot Care - McAllen Office
    • San Antonio, Texas, United States, 78229
      • Endeavor Clinical Trials PA
  • Virginia
    • Charlottesville, Virginia, United States, 22908-0709
      • University of Virginia
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subjects must satisfy the following criteria to be enrolled in the study:

  1. Males and females, 18 to 80 years of age 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 2
  5. Ischemic or neuro-ischemic 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.
  6. Peripheral arterial disease with ankle-brachial index > 0.5 and ≤ 0.9 or toe-brachial index > 0.35 and ≤ 0.7.
  7. No planned revascularization or amputation over the next 3 months after Screening visit, in the opinion of the Investigator.
  8. Screening should not begin until at least 2 weeks after a failed reperfusion intervention and at least 2 months after a successful mechanical intervention.
  9. Subject can have stable angina, (Canadian Cardiovascular Society (CCS) Class I-II angina (Appendix H).
  10. Subjects should be receiving appropriate medical therapy for hypertension and diabetes.
  11. A female of childbearing potential [FCBP] 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; intrauterine device [IUD]; barrier contraceptive with spermicide or vasectomized partner for the duration of the study and the follow-up period.

  12. 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:

• The presence of any of the following will exclude a subject from enrollment:

  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. Subjects whom, in the judgment of the Investigator, are at elevated risk for the development of a malignancy. This judgment may be based on family history, history of industrial exposures, smoking history or other cancer risk factors.
  5. Known to be positive for human immunodeficiency virus.
  6. Pregnant or lactating females.
  7. Subjects with a body mass index > 40 at Screening.
  8. Aspartate transaminase (AST) or Alanine transaminase (ALT) > 2.5 x the upper limit of normal (ULN) at Screening.
  9. Estimated Glomerular Filtration Rate (eGFR) < 45 mL/min/1.73 m2 at Screening calculated using the Modification of Diet in Renal Disease Study equation (Levey, 2006) or history of eGFR decline > 15 mL/min/1.73 m2 in the past year.
  10. Alkaline phosphatase > 2.5 x the ULN at Screening.
  11. Bilirubin level > 2 mg/dL (unless subject has known Gilbert's disease) at Screening.
  12. Untreated chronic infection or treatment of any infection with systemic antibiotics, including the ulcer site, within 4 weeks prior to dosing with investigational product [IP].
  13. Known osteomyelitis.
  14. Ulcer that has decreased or increased in size by ≥ 50% during the screening period.
  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 > 9%).
  17. Untreated proliferative retinopathy.
  18. History of malignant ventricular arrhythmia, CCS Class III-IV angina pectoris, myocardial infarction/PCI (percutaneous coronary intervention)/CABG (coronary artery bypass graft) in the preceding 6 months, pending coronary revascularization in the following 2 months, transient ischemic attack/cerebrovascular accident in the preceding 6 months, and/or New York Heart Association [NYHA] Stage III or IV congestive heart failure, (Appendix C).
  19. Abnormal ECG: new bundle branch block (BBB) ≥ 120 msec in the preceding 3 months; QTcB and/or QTcF > 480 msec or QTcB and/or QTcF ≥ 500 msec with old BBB. Patients with a potential risk for Torsades des Pointes should not be enrolled.
  20. Uncontrolled hypercoagulation.
  21. Life expectancy less than 2 years due to concomitant illnesses.
  22. In the opinion of the Investigator, the subject is unsuitable for cellular therapy.
  23. History of malignancy within 5 years 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. Disorders or allergies precluding the use of radiographic contrast or renal insufficiency severe enough to contraindicate the use of radiographic contrast.
  26. 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.
  27. Subject has received previous gene or cell therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 3 x10^6 cells; Subjects received PDA-002 (human placenta-derived cells) administered intramuscularly on Study Days 1 and 8 at a dose level of 3 × 10^6 cells.	Biological: PDA-002; Human placenta-derived cells administered intramuscularly on Study Days 1 and 8.
Experimental: 10 x 10^6 cells; Subjects received PDA-002 (human placenta-derived cells) administered intramuscularly on Study Days 1 and 8 at a dose level of 10 × 10^6 cells.	Biological: PDA-002; Human placenta-derived cells administered intramuscularly on Study Days 1 and 8.
Experimental: 30 x 10^6 cells; Subjects received PDA-002 (human placenta-derived cells) administered intramuscularly on Study Days 1 and 8 at a dose level of 30 × 10^6 cells.	Biological: PDA-002; Human placenta-derived cells administered intramuscularly on Study Days 1 and 8.
Experimental: 100 x 10^6 cells; Subjects received PDA-002 (human placenta-derived cells) administered intramuscularly on Study Days 1 and 8 at a dose level of 100 × 10^6 cells.	Biological: PDA-002; Human placenta-derived cells administered intramuscularly on Study Days 1 and 8.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Limiting Toxicity (DLTs)	Number of participants with dose-limiting toxicities following intramuscular administration of PDA-002. Dose-limiting toxicity was used to evaluate maximum tolerated dose.	Through Day 15 following initial dosing
Treatment-Emergent Adverse Events (TEAEs)	Number of participants with treatment-emergent adverse events following administration of PDA-002.	From first dose through month 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ankle-brachial index (ABI)	at the ankle by the systolic blood pressures (Doppler technique) in the arm.	Approximately 2 years
Toe-brachial index (TBI)	To assess changes in the TBI which is calculated by dividing the systolic blood pressure at the toe by the systolic blood pressures (Doppler technique) in the arm.	Approximately 2 years

Collaborators and Investigators

• Sponsor: Celularity Incorporated
• Investigators: Study Director: Sharmila Koppisetti, MD, Celularity Incorporated

Publications and helpful links

General Publications

• Francki A, Labazzo K, He S, Baum EZ, Abbot SE, Herzberg U, Hofgartner W, Hariri R; Celgene Cellular Therapeutics Research Group. Angiogenic properties of human placenta-derived adherent cells and efficacy in hindlimb ischemia. J Vasc Surg. 2016 Sep;64(3):746-756.e1. doi: 10.1016/j.jvs.2015.04.387. Epub 2015 Jun 6.
• Wu SC, Pollak R, Frykberg RG, Zhou W, Karnoub M, Jankovic V, Fischkoff SA, Chitkara D. Safety and efficacy of intramuscular human placenta-derived mesenchymal stromal-like cells (cenplacel [PDA-002]) in patients who have a diabetic foot ulcer with peripheral arterial disease. Int Wound J. 2017 Oct;14(5):823-829. doi: 10.1111/iwj.12715. Epub 2017 Jan 30.

Helpful Links

• publication

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2013
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): March 14, 2017

Study Registration Dates

• First Submitted: May 17, 2013
• First Submitted That Met QC Criteria: May 17, 2013
• First Posted (Estimated): May 21, 2013

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: May 8, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Peripheral arterial disease; PAD; DFU; diabetic foot ulcer
• Additional Relevant MeSH Terms: Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases; Diabetes Mellitus; Diabetic Angiopathies; Diabetes Complications; Skin Diseases; Skin Ulcer; Leg Ulcer; Diabetic Neuropathies; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Peripheral Vascular Diseases; Foot Ulcer; Skin and Connective Tissue Diseases; Diabetic Foot; Peripheral Arterial Disease
• Other Study ID Numbers: CCT-PDA-002-DFU-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No