Efficacy and Safety of Intramuscular PDA-002 in Subjects Who Have Diabetic Foot Ulcer With and Without Peripheral Arterial Disease
- Conditions
- Peripheral Arterial DiseaseDiabetic Foot
- Interventions
- Other: PlaceboBiological: 3 x 10^6 cellsBiological: 10 x 10^6 cellsBiological: 30 x 10^6 cells
- Registration Number
- NCT02264288
- Lead Sponsor
- Celularity Incorporated
- Brief Summary
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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 159
- Males and females, at least 18 years of age or older at the time of signing the informed consent document.
- Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures are conducted.
- Able to adhere to the study visit schedule and other protocol requirements.
- Diabetes mellitus Type 1 or Type 2.
- 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.
- No planned revascularization or amputation over the next 3 months after Screening visit, in the opinion of the Investigator.
- Screening should not begin until at least 14 days after a failed reperfusion intervention and at least 30 days after a successful reperfusion intervention.
- Subjects should be receiving appropriate medical therapy for hypertension and diabetes any other chronic medical conditions for which they require ongoing care.
- 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.
- 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.
- Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
- 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.
- Any condition that confounds the ability to interpret data from the study.
- Pregnant or lactating females.
- Subjects with a body mass index > 45 kg/m2 at Screening.
- AST (SGOT) or ALT (SGPT) > 2.5 x the upper limit of normal (ULN) at Screening.
- Patient on renal dialysis for abnormal kidney function.
- An ABI < 0.4 and or TBI < 0.3 in the leg with the index ulcer.
- Bilirubin level > 2 mg/dL (unless subject has known Gilbert's disease) at Screening.
- 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.
- 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.
- Index ulcer that has decreased or increased in size by ≥ 30% during the Screening/Run-In/ Pre-Treatment Period.
- Active Charcot Neuroarthropathy in the foot with the index ulcer
- Pain at rest due to limb ischemia.
- 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).
- Poorly controlled diabetes mellitus (hemoglobin A1c > 12% or a screening serum glucose of ≥ 300mg/dl).
- Untreated proliferative retinopathy.
- 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.
- Abnormal ECG: new right bundle branch block (BBB) ≥ 120 msec in the preceding 3 months prior to signing the ICF.
- Uncontrolled hypercoagulation syndrome.
- Life expectancy less than at 2 years at the time of signing the ICF due to concomitant illnesses.
- In the opinion of the Investigator, the subject is unsuitable for cellular therapy.
- 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.
- History of hypersensitivity to any of the components of the product formulation (including bovine or porcine products, dextran 40, and dimethyl sulfoxide [DMSO]).
- 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.
- Subject has received previous investigational gene or cell therapy.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Identically matching placebo administered IM on Study Days 1 and 8 3 x 10^6 cells 3 x 10^6 cells Human Placenta Derived cells (PDA-002) administered intramuscularly (IM) on Study Days 1 and 8 10 x 10^6 cells 10 x 10^6 cells 10 x 10\^6 Human Placenta Derived cells (PDA-002) administered intramuscularly on Study Days 1 and 8 30 x 10^6 cells 30 x 10^6 cells 30 x 10\^6 Human Placenta Derived cells (PDA-002) administered intramuscularly on Study Days 1 and 8
- Primary Outcome Measures
Name Time Method Complete wound closure of the index ulcer Up to 4 months Complete wound closure is defined as closure of the index ulcer and retaining wound closure for the subsequent 4 weeks
Safety (adverse events [type, frequency, and severity of AEs, and relationship of AEs to study drug], laboratory abnormalities, and hospitalizations Up to 24 months An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study.
- Secondary Outcome Measures
Name Time Method Time to ulcer closure Up to 6 months The time period for the index ulcer to close
Ankle Brachial Index (ABI ) and Toe-Brachial Index (TBI) Up to 6 months 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
50% Closure of Index Ulcer Up to 24 months The proportion of subjects with at least 50% closure of the index ulcer
Transcutaneous oxygen Up to 6 months Transcutaneous oxygen measurements determine the oxygen level in tissue below the skin
Time to amputation, ulcer opening closing, gangrene and infection Up to 24 months 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
Wagner Grading Scale Up to 24 months 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).
Rutherford Criteria Up to 6 months The Rutherford classification is a clinical staging system for describing peripheral arterial disease.
36-item Short Form Health Survey (SF-36) Up to 6 months A validated measurement of health related quality of life
Diabetic Foot Ulcer Scale Short Form (DFS-SF) index ulcer Up to 6 months A measurement of the impact of diabetic foot ulcer on a patient's quality of life.
Patient Global Impression of Change in Neuropathy (PGICN) Up to 24 months Assessment of changes in neuropathy over time
European Quality of Life: EuroQOL-5D- health utility index assessment (EQ-5D) Up to 6 months A standardized instrument used as a measure of health outcome
Number of all ulcers Up to 24 months The total number of ulcers
Leg rest pain score Up to 24 months A visual analog scale (VAS) graded from 0 (pain free) to Grade 10 (maximum pain)
Trial Locations
- Locations (55)
UCLA
🇺🇸Los Angeles, California, United States
University of Pennsylvania Health Systems
🇺🇸Philadelphia, Pennsylvania, United States
Premier Vein and Vascular Center
🇺🇸Houston, Texas, United States
Clinical Research of West Florida Inc - Clearwater
🇺🇸Clearwater, Florida, United States
East Valley Foot and Ankle Specialist
🇺🇸Mesa, Arizona, United States
Limb Preservation Platform, INC.
🇺🇸Fresno, California, United States
TFi Medical
🇺🇸Mobile, Alabama, United States
Aung Foothealth Clinics and Advanced Wound Care Center
🇺🇸Tucson, Arizona, United States
Reliance Clinical Research
🇺🇸Chino, California, United States
Center for Clinical Research Inc.
🇺🇸Castro Valley, California, United States
Jeffrey A Klemes DPM
🇺🇸Beverly Hills, California, United States
Foot and Ankle Clinic
🇺🇸Los Angeles, California, United States
VA Palo Alto Health Care System
🇺🇸Palo Alto, California, United States
Stanford University
🇺🇸Stanford, California, United States
Georgetown University Medical Center Lombardi Cancer Center
🇺🇸Washington, District of Columbia, United States
Barry University
🇺🇸Fort Lauderdale, Florida, United States
The Research Center
🇺🇸Hialeah, Florida, United States
Solutions Through Advanced Research Inc.
🇺🇸Jacksonville, Florida, United States
University of Miami
🇺🇸Miami, Florida, United States
GF Professional Research Group Corporation
🇺🇸Miami Lakes, Florida, United States
University of Illinois at Chicago Cancer Center
🇺🇸Chicago, Illinois, United States
Well Pharma Medical Research Corporation
🇺🇸Miami, Florida, United States
Med-Care Research Inc
🇺🇸North Miami Beach, Florida, United States
Podiatry 1st
🇺🇸Belleville, Illinois, United States
Weill Foot & Ankle Institute
🇺🇸Des Plaines, Illinois, United States
Southern Illinois University
🇺🇸Springfield, Illinois, United States
Rosalind Franklin University of Medicine and Science
🇺🇸North Chicago, Illinois, United States
Sinai Hospital of Baltimore
🇺🇸Baltimore, Maryland, United States
Revive Research Institute
🇺🇸Sterling Heights, Michigan, United States
Northwest Hospital
🇺🇸Randallstown, Maryland, United States
Office of Michael J. De Marco, DPM
🇺🇸Tinton Falls, New Jersey, United States
Ocean City Foot and Ankle Assoc
🇺🇸Toms River, New Jersey, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Clinical Research Associates of Central Pennsylvania
🇺🇸Duncansville, Pennsylvania, United States
Syracuse VA Medical Center
🇺🇸Syracuse, New York, United States
Complete Family Foot Care - McAllen Office
🇺🇸McAllen, Texas, United States
Carilion Clinic
🇺🇸Roanoke, Virginia, United States
1Foot 2Foot Centre for Foot & Ankle Care PC
🇺🇸Suffolk, Virginia, United States
Milwaukee Foot & Ankle Specialists
🇺🇸Wauwatosa, Wisconsin, United States
Carl T. Hayden Veterans Affairs Medical Center
🇺🇸Phoenix, Arizona, United States
Arizona Arthritis and Rheumatology Research, PLLC
🇺🇸Phoenix, Arizona, United States
Endeavor Clinical Trials PA
🇺🇸San Antonio, Texas, United States
SAM Clinical Research Center
🇺🇸San Antonio, Texas, United States
Advanced Foot & Ankle Center
🇺🇸Salt Lake City, Utah, United States
Cardiology PC
🇺🇸Birmingham, Alabama, United States
CGH Medical Center Main Clinic
🇺🇸Sterling, Illinois, United States
Northeast Arkansas Baptist Clinic
🇺🇸Jonesboro, Arkansas, United States
Englewood Hospital and Medical Center
🇺🇸Englewood, New Jersey, United States
Hamilton Foot Care
🇺🇸Baltimore, Maryland, United States
University of Florida
🇺🇸Jacksonville, Florida, United States
Florida Research Network, LLC
🇺🇸Gainesville, Florida, United States
UNC Hospitals University of North Carolina
🇺🇸Chapel Hill, North Carolina, United States
Foot and Ankle Center of Illinois
🇺🇸Springfield, Illinois, United States
Animas Foot and Ankle
🇺🇸Gallup, New Mexico, United States
Office of Gerard J. Furst, DPM, PLLC
🇺🇸East Setauket, New York, United States