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

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

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).

Study Overview

• Status: Terminated
• Conditions: Diabetic Foot; Peripheral Arterial Disease
• Intervention / Treatment: Biological: 3 x 10^6 cells; Biological: 30 x 10^6 cells; Biological: 10 x 10^6 cells; Other: Placebo

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

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35211
      • Cardiology PC
    • Mobile, Alabama, United States, 36608
      • TFi Medical
  • Arizona
    • Mesa, Arizona, United States, 85206
      • East Valley Foot and Ankle Specialist
    • Phoenix, Arizona, United States, 85012
      • Carl T. Hayden Veterans Affairs Medical Center
    • Phoenix, Arizona, United States, 85023
      • Arizona Arthritis and Rheumatology Research, PLLC
    • Tucson, Arizona, United States, 85710
      • Aung Foothealth Clinics and Advanced Wound Care Center
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • Northeast Arkansas Baptist Clinic
  • California
    • Beverly Hills, California, United States, 90211
      • Jeffrey A Klemes DPM
    • Castro Valley, California, United States, 94546-5306
      • Center for Clinical Research Inc.
    • Chino, California, United States, 91710
      • Reliance Clinical Research
    • Fresno, California, United States, 93720
      • Limb Preservation Platform, Inc.
    • Los Angeles, California, United States, 90095
      • UCLA
    • Los Angeles, California, United States, 90010
      • Foot and Ankle Clinic
    • Palo Alto, California, United States, 94304
      • VA Palo Alto Health Care System
    • Stanford, California, United States, 94035-5821
      • Stanford University
  • District of Columbia
    • Washington, 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
    • Fort Lauderdale, Florida, United States, 33321
      • Barry University
    • 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
    • North Miami Beach, Florida, United States, 33162
      • Med-Care Research Inc
  • Illinois
    • Belleville, Illinois, United States, 62226
      • Podiatry 1st
    • Chicago, Illinois, United States, 60612
      • University of Illinois at Chicago Cancer Center
    • 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, 62702
      • Southern Illinois University
    • 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
    • Tinton Falls, New Jersey, United States, 07724
      • Office of Michael J. De Marco, DPM
    • Toms River, New Jersey, United States, 08753
      • Ocean City Foot and Ankle Assoc
  • New Mexico
    • Gallup, New Mexico, United States, 87301
      • Animas Foot and Ankle
  • New York
    • East Setauket, New York, United States, 11733
      • Office of Gerard J. Furst, DPM, PLLC
    • Syracuse, New York, United States, 13210
      • Syracuse VA Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7010
      • UNC Hospitals University of North Carolina
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Clinical Research Associates of Central Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Health Systems
  • Texas
    • Dallas, Texas, United States, 75390-9068
      • University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77084
      • Premier Vein and Vascular Center
    • McAllen, Texas, United States, 78501-2930
      • Complete Family Foot Care - McAllen Office
    • 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
• Genders Eligible for Study: All

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
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 3 x 10^6 cells; Human Placenta Derived cells (PDA-002) administered intramuscularly (IM) on Study Days 1 and 8	Biological: 3 x 10^6 cells; 3 x 10^6 cells administered on Study Days 1 and 8; Other Names: PDA-002
EXPERIMENTAL: 10 x 10^6 cells; 10 x 10^6 Human Placenta Derived cells (PDA-002) administered intramuscularly on Study Days 1 and 8	Biological: 10 x 10^6 cells; 10 x 10^6 Human Placenta Derived cells (PDA-002) administered on Study Days 1 and 8; Other Names: PDA-002
EXPERIMENTAL: 30 x 10^6 cells; 30 x 10^6 Human Placenta Derived cells (PDA-002) administered intramuscularly on Study Days 1 and 8	Biological: 30 x 10^6 cells; 30 x 10^6 Human Placenta Derived cells (PDA-002) administered intramuscularly on Study Days 1 and 8; Other Names: PDA-002
PLACEBO_COMPARATOR: Placebo; Identically matching placebo administered IM on Study Days 1 and 8	Other: Placebo; Identical matching placebo administered IM on Study Days 1 and 8

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete wound closure of the index ulcer	Complete wound closure is defined as closure of the index ulcer and retaining wound closure for the subsequent 4 weeks	Up to 4 months
Safety (adverse events [type, frequency, and severity of AEs, and relationship of AEs to study drug], laboratory abnormalities, and hospitalizations	An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study.	Up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to ulcer closure	The time period for the index ulcer to close	Up to 6 months
Ankle Brachial Index (ABI ) and Toe-Brachial Index (TBI)	ABI and TBI will be calculated by dividing the systolic blood pressure at the ankle or toe by the systolic blood pressures (Doppler technique) in the arm	Up to 6 months
50% Closure of Index Ulcer	The proportion of subjects with at least 50% closure of the index ulcer	Up to 24 months
Transcutaneous oxygen	Transcutaneous oxygen measurements determine the oxygen level in tissue below the skin	Up to 6 months
Time to amputation, ulcer opening closing, gangrene and infection	Time to major amputation (above the ankle) of treated leg, minor amputations, to re-opening of ulcer, time to doubling / halving of index ulcer total surface area from baseline, de novo gangrene and foot wound infection	Up to 24 months
Wagner Grading Scale	The Wagner system assesses ulcer depth and the presence of osteomyelitis or gangrene by using the following grades: grade 0 (pre-or postulcerative lesion), grade 1 (partial/full thickness ulcer), grade 2 (probing to tendon or capsule), grade 3 (deep with osteitis), grade 4 (partial foot gangrene), and grade 5 (whole foot gangrene).	Up to 24 months
Rutherford Criteria	The Rutherford classification is a clinical staging system for describing peripheral arterial disease.	Up to 6 months
36-item Short Form Health Survey (SF-36)	A validated measurement of health related quality of life	Up to 6 months
Diabetic Foot Ulcer Scale Short Form (DFS-SF) index ulcer	A measurement of the impact of diabetic foot ulcer on a patient's quality of life.	Up to 6 months
Patient Global Impression of Change in Neuropathy (PGICN)	Assessment of changes in neuropathy over time	Up to 24 months
European Quality of Life: EuroQOL-5D- health utility index assessment (EQ-5D)	A standardized instrument used as a measure of health outcome	Up to 6 months
Number of all ulcers	The total number of ulcers	Up to 24 months
Leg rest pain score	A visual analog scale (VAS) graded from 0 (pain free) to Grade 10 (maximum pain)	Up to 24 months

Collaborators and Investigators

• Sponsor: Celularity Incorporated

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 23, 2014
• Primary Completion (ACTUAL): February 28, 2018
• Study Completion (ACTUAL): February 28, 2018

Study Registration Dates

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

Study Record Updates

• Last Update Posted (ACTUAL): July 22, 2020
• Last Update Submitted That Met QC Criteria: July 20, 2020
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Peripheral Arterial Disease; Diabetic Foot
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Endocrine System Diseases; Diabetic Angiopathies; Leg Ulcer; Skin Ulcer; Diabetes Complications; Diabetes Mellitus; Diabetic Neuropathies; Foot Diseases; Atherosclerosis; Diabetic Foot; Foot Ulcer; Peripheral Arterial Disease; Peripheral Vascular Diseases
• Other Study ID Numbers: CCT-PDA-002-DFU-002