Efficacy and Safety of Intramuscular PDA-002 in Subjects With Diabetic Foot Ulcer With and Without PAD. (DFU-002)

A Phase 2 Multicenter, Randomized, Double-Blind, Placebo-Controlled, Dose Range Finding Study to Evaluate the Efficacy and Safety of Intramuscular Injection of Human Placenta-Derived Cells (PDA-002) in Subjects With Diabetic Foot Ulcer With and Without Peripheral Arterial Disease.

This is a Phase 2, multicenter, randomized, double-blind, placebo-controlled, dose-ranging study evaluating the efficacy and safety of intramuscular administration of human placenta-derived cells (PDA-002) in subjects with diabetic foot ulcers (DFU), including subjects with and without peripheral arterial disease (PAD). Subjects were randomized to receive one of three dose levels of PDA-002 or placebo. Randomization was stratified by PAD status. The study evaluated wound healing and safety outcomes over the follow-up period.

Study Overview

• Status: Terminated
• Conditions: Diabetic Foot; Peripheral Arterial Disease
• Intervention / Treatment: Biological: PDA-002; Other: Placebo

Detailed Description

This Phase 2 study was designed to evaluate the efficacy and safety of PDA-002, a human placenta-derived cell therapy, administered via intramuscular injection in subjects with diabetic foot ulcers (DFU). The study included subjects with and without peripheral arterial disease (PAD), reflecting a broader DFU population.

Subjects were randomized in a parallel-group design to receive PDA-002 at one of three dose levels (3 × 10^6, 10 × 10^6, or 30 × 10^6 cells) or matching placebo, administered on Study Days 1 and 8. Randomization was stratified by PAD status.

The primary objective was to assess efficacy in terms of wound healing outcomes, with secondary objectives evaluating vascular parameters such as ankle-brachial index (ABI), toe-brachial index (TBI), and transcutaneous oxygen pressure (TcPO2), as well as overall safety.

The study was terminated early due to a business decision; however, subjects were followed according to protocol-defined follow-up schedules.

• Study Type: Interventional
• Enrollment (Actual): 159
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35211
      • Cardiology PC
  • Arizona
    • Mesa, Arizona, United States, 85206
      • Swagel wootoon hiatt eye center
    • Phoenix, Arizona, United States, 85012
      • Carl T. Hayden Veterans Affairs Medical Center
    • Phoenix, Arizona, United States, 85023
      • Arizona Arthritis and Rheumatology Research, PLLC
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • NEA Baptist Clinic
  • California
    • Beverly Hills, California, United States, 90211
      • Jeffrey A Klemes DPM
    • Chino, California, United States, 91710
      • Reliance Clinical Research
    • Fresno, California, United States, 93720
      • Limb Preservation Platform, INC.
    • Los Angeles, California, United States, 90057
      • Foot and Ankle Clinic
    • Palo Alto, California, United States, 94304
      • VA Palo Alto Health Care System
    • San Francisco, California, United States, 94115
      • Center for Clinical Research Inc.
    • Stanford, California, United States, 94063
      • Stanford University
  • Colorado
    • Durango, Colorado, United States, 81301
      • Animas Foot and Ankle
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007-2197
      • Georgetown University Medical Center Lombardi Cancer Center
  • Florida
    • Clearwater, Florida, United States, 33765
      • Clinical Research of West Florida Inc - Clearwater
    • Gainesville, Florida, United States, 32605
      • Florida Research Network, LLC
    • Hialeah, Florida, United States, 33012
      • The Research Center
    • Jacksonville, Florida, United States, 32209
      • University of Florida
    • Jacksonville, Florida, United States, 32258
      • Solutions Through Advanced Research Inc.
    • Miami, Florida, United States, 33136
      • University of Miami
    • Miami, Florida, United States, 33143
      • Well Pharma Medical Research Corporation
    • Miami Lakes, Florida, United States, 33016
      • GF Professional Research Group Corporation
  • Illinois
    • Belleville, Illinois, United States, 62226
      • Podiatry 1st
    • Des Plaines, Illinois, United States, 60016
      • Weill Foot & Ankle Institute
    • North Chicago, Illinois, United States, 60064
      • Rosalind Franklin University of Medicine and Science
    • Springfield, Illinois, United States, 62704
      • Foot and Ankle Center of Illinois
    • Sterling, Illinois, United States, 61081
      • CGH Medical Center Main Clinic
  • Maryland
    • Baltimore, Maryland, United States, 21215
      • Sinai Hospital of Baltimore
    • Baltimore, Maryland, United States, 21214
      • Hamilton Foot Care
    • Randallstown, Maryland, United States, 21133
      • Northwest Hospital
  • Michigan
    • Sterling Heights, Michigan, United States, 48313
      • Revive Research Institute
  • New Jersey
    • Englewood, New Jersey, United States, 07631
      • Englewood Hospital and Medical Center
    • Newark, New Jersey, United States, 07102
      • Office of Michael J. De Marco, DPM
    • Toms River, New Jersey, United States, 08753
      • Ocean City Foot and Ankle Assoc
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7010
      • UNC Hospitals University of North Carolina
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Bert J Altmanshofer and associates, LTD
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Health Systems
  • Texas
    • Houston, Texas, United States, 77084
      • Premier Vein and Vascular Center
    • McAllen, Texas, United States, 78501-2930
      • Futuro Clinical Trials
    • San Antonio, Texas, United States, 78229
      • SAM Clinical Research Center
    • San Antonio, Texas, United States, 78229
      • Endeavor Clinical Trials PA
  • Utah
    • Salt Lake City, Utah, United States, 84102
      • Advanced Foot & Ankle Center
  • Virginia
    • Roanoke, Virginia, United States, 24013
      • Carilion Clinic
    • Suffolk, Virginia, United States, 23434
      • 1Foot 2Foot Centre for Foot & Ankle Care PC
  • Wisconsin
    • Wauwatosa, Wisconsin, United States, 53226
      • Milwaukee Foot & Ankle Specialists

Participation Criteria

Eligibility Criteria

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

Description

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 resection.
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 failure.
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 illnesses.
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 study.
26. Subject has received previous investigational gene or cell therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PDA-002 3 x 10^6 cells; Subjects randomized to receive PDA-002 at a dose of 3 × 10^6 cells administered intramuscularly on Study Days 1 and 8. Randomization was stratified by peripheral arterial disease (PAD) status (subjects with PAD and subjects without PAD).	Biological: PDA-002; Human placenta-derived cells administered intramuscularly on Study Days 1 and 8 at assigned dose levels.
Experimental: PDA-002 10 x 10^6 cells; Subjects randomized to receive PDA-002 at a dose of 10 × 10^6 cells administered intramuscularly on Study Days 1 and 8. Randomization was stratified by peripheral arterial disease (PAD) status (subjects with PAD and subjects without PAD).	Biological: PDA-002; Human placenta-derived cells administered intramuscularly on Study Days 1 and 8 at assigned dose levels.
Experimental: PDA-002 30 x 10^6 cells; Subjects randomized to receive PDA-002 at a dose of 30 × 10^6 cells administered intramuscularly on Study Days 1 and 8. Randomization was stratified by peripheral arterial disease (PAD) status (subjects with PAD and subjects without PAD).	Biological: PDA-002; Human placenta-derived cells administered intramuscularly on Study Days 1 and 8 at assigned dose levels.
Placebo Comparator: Placebo; Subjects randomized to receive matching placebo administered intramuscularly on Study Days 1 and 8. Randomization was stratified by peripheral arterial disease (PAD) status.	Other: Placebo; Matching placebo administered intramuscularly on Study Days 1 and 8.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects With Complete Wound Closure of the Index Ulcer Within 3 Months	Complete wound closure is defined as closure of the index ulcer within 3 months after dosing and retaining wound closure for the subsequent 4 weeks.	Within 3 months after dosing, with confirmation over the subsequent 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects With Complete Wound Closure of the Index Ulcer Within 3 Months by PAD Status	Results are presented by baseline peripheral arterial disease (PAD) status (subjects with PAD and subjects without PAD). Complete wound closure is defined as closure of the index ulcer and retaining wound closure for the subsequent 4 weeks.	Within 3 months after dosing, with confirmation over the subsequent 4 weeks
Percentage of Subjects With Improvement in Rutherford Classification at Month 3 in Subjects With PAD	Responders are defined as subjects who improved by at least 1 numeric Rutherford category from baseline. Results are reported for subjects with peripheral arterial disease (PAD).	Month 3

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Toe-Brachial Index (TBI) at Month 6	TBI was calculated by dividing toe systolic blood pressure by brachial systolic blood pressure using Doppler technique. The average value was used if multiple measurements were available at a study visit.	Baseline and Month 6
Change From Baseline in Transcutaneous Oxygen Pressure (TcPO2) at Month 6	Transcutaneous oxygen pressure (TcPO2) measurements were used to assess tissue oxygenation. Difference in TcPO2 was calculated as TcPO2 in elevated position minus TcPO2 in supine position.	Baseline and Month 6
Change From Baseline in Ankle-Brachial Index (ABI) at Month 6	ABI was calculated by dividing the systolic blood pressure at the ankle or toe by the systolic blood pressure in the arm using Doppler technique.	Baseline and Month 6
Percentage of Subjects With Wagner Grade 0 for the Index Ulcer at Month 6	Wagner Grading Scale scores range from Grade 0 (no open lesion) to Grade 5 (extensive gangrene of the entire foot). Lower grades indicate less severe ulceration and better clinical status.	Month 6

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Pollak R, Anderson J, Altmanshofer B, Caporusso J, Fantini G, Koppisetti S, Brigido S, Hariri R. Human Placenta-Derived Cells (PDA-002) in Diabetic Foot Ulcer Patients With and Without Peripheral Artery Disease: A Phase 2 Multi-Center, Randomised, Double-Blind, Placebo-Controlled Trial. Int Wound J. 2025 Oct;22(10):e70769. doi: 10.1111/iwj.70769.

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2014
• Primary Completion (Actual): February 27, 2018
• Study Completion (Actual): February 27, 2018

Study Registration Dates

• First Submitted: October 2, 2014
• First Submitted That Met QC Criteria: October 9, 2014
• First Posted (Estimated): October 15, 2014

Study Record Updates

• Last Update Posted (Actual): June 12, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Peripheral Arterial Disease; Diabetic Foot; Placenta Derived Stem Cells
• 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-002

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