Clinical trial NCT02264288: Efficacy and Safety of Intramuscular PDA-002 in Subjects Who Have Diabetic Foot Ulcer With and Without Peripheral Arterial Disease
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Peripheral Arterial Disease
Diabetic Foot
Keywords: Peripheral Arterial Disease
Diabetic Foot
Lead sponsor: Celularity Incorporated
Sponsor class: INDUSTRY
First posted: 2014-10-15
Enrollment: 159
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Complete wound closure of the index ulcer
timeFrame: Up to 4 months
measure: Safety (adverse events [type, frequency, and severity of AEs, and relationship of AEs to study drug], laboratory abnormalities, and hospitalizations
timeFrame: Up to 24 months
Secondary outcomes:
measure: Time to ulcer closure
timeFrame: Up to 6 months
measure: Ankle Brachial Index (ABI ) and Toe-Brachial Index (TBI)
timeFrame: Up to 6 months
measure: 50% Closure of Index Ulcer
timeFrame: Up to 24 months
measure: Transcutaneous oxygen
timeFrame: Up to 6 months
measure: Time to amputation, ulcer opening closing, gangrene and infection
timeFrame: Up to 24 months
measure: Wagner Grading Scale
timeFrame: Up to 24 months
measure: Rutherford Criteria
timeFrame: Up to 6 months
measure: 36-item Short Form Health Survey (SF-36)
timeFrame: Up to 6 months
measure: Diabetic Foot Ulcer Scale Short Form (DFS-SF) index ulcer
timeFrame: Up to 6 months
measure: Patient Global Impression of Change in Neuropathy (PGICN)
timeFrame: Up to 24 months
measure: European Quality of Life: EuroQOL-5D- health utility index assessment (EQ-5D)
timeFrame: Up to 6 months
measure: Number of all ulcers
timeFrame: Up to 24 months
measure: Leg rest pain score
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Cardiology PC
state: Alabama
city: Mobile
country: United States
facility: TFi Medical
state: Alabama
city: Mesa
country: United States
facility: East Valley Foot and Ankle Specialist
state: Arizona
city: Phoenix
country: United States
facility: Carl T. Hayden Veterans Affairs Medical Center
state: Arizona
city: Phoenix
country: United States
facility: Arizona Arthritis and Rheumatology Research, PLLC
state: Arizona
city: Tucson
country: United States
facility: Aung Foothealth Clinics and Advanced Wound Care Center
state: Arizona
city: Jonesboro
country: United States
facility: Northeast Arkansas Baptist Clinic
state: Arkansas
city: Beverly Hills
country: United States
facility: Jeffrey A Klemes DPM
state: California
city: Castro Valley
country: United States
facility: Center for Clinical Research Inc.
state: California
city: Chino
country: United States
facility: Reliance Clinical Research
state: California
city: Fresno
country: United States
facility: Limb Preservation Platform, INC.
state: California
city: Los Angeles
country: United States
facility: Foot and Ankle Clinic
state: California
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Palo Alto
country: United States
facility: VA Palo Alto Health Care System
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Washington
country: United States
facility: Georgetown University Medical Center Lombardi Cancer Center
state: District of Columbia
city: Clearwater
country: United States
facility: Clinical Research of West Florida Inc - Clearwater
state: Florida
city: Fort Lauderdale
country: United States
facility: Barry University
state: Florida
city: Gainesville
country: United States
facility: Florida Research Network, LLC
state: Florida
city: Hialeah
country: United States
facility: The Research Center
state: Florida
city: Jacksonville
country: United States
facility: University of Florida
state: Florida
city: Jacksonville
country: United States
facility: Solutions Through Advanced Research Inc.
state: Florida
city: Miami Lakes
country: United States
facility: GF Professional Research Group Corporation
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Miami
country: United States
facility: Well Pharma Medical Research Corporation
state: Florida
city: North Miami Beach
country: United States
facility: Med-Care Research Inc
state: Florida
city: Belleville
country: United States
facility: Podiatry 1st
state: Illinois
city: Chicago
country: United States
facility: University of Illinois at Chicago Cancer Center
state: Illinois
city: Des Plaines
country: United States
facility: Weill Foot & Ankle Institute
state: Illinois
city: North Chicago
country: United States
facility: Rosalind Franklin University of Medicine and Science
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University
state: Illinois
city: Springfield
country: United States
facility: Foot and Ankle Center of Illinois
state: Illinois
city: Sterling
country: United States
facility: CGH Medical Center Main Clinic
state: Illinois
city: Baltimore
country: United States
facility: Hamilton Foot Care
state: Maryland
city: Baltimore
country: United States
facility: Sinai Hospital of Baltimore
state: Maryland
city: Randallstown
country: United States
facility: Northwest Hospital
state: Maryland
city: Sterling Heights
country: United States
facility: Revive Research Institute
state: Michigan
city: Englewood
country: United States
facility: Englewood Hospital and Medical Center
state: New Jersey
city: Tinton Falls
country: United States
facility: Office of Michael J. De Marco, DPM
state: New Jersey
city: Toms River
country: United States
facility: Ocean City Foot and Ankle Assoc
state: New Jersey
city: Gallup
country: United States
facility: Animas Foot and Ankle
state: New Mexico
city: East Setauket
country: United States
facility: Office of Gerard J. Furst, DPM, PLLC
state: New York
city: Syracuse
country: United States
facility: Syracuse VA Medical Center
state: New York
city: Chapel Hill
country: United States
facility: UNC Hospitals University of North Carolina
state: North Carolina
city: Duncansville
country: United States
facility: Clinical Research Associates of Central Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania Health Systems
state: Pennsylvania
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Premier Vein and Vascular Center
state: Texas
city: McAllen
country: United States
facility: Complete Family Foot Care - McAllen Office
state: Texas
city: San Antonio
country: United States
facility: Endeavor Clinical Trials PA
state: Texas
city: San Antonio
country: United States
facility: SAM Clinical Research Center
state: Texas
city: Salt Lake City
country: United States
facility: Advanced Foot & Ankle Center
state: Utah
city: Roanoke
country: United States
facility: Carilion Clinic
state: Virginia
city: Suffolk
country: United States
facility: 1Foot 2Foot Centre for Foot & Ankle Care PC
state: Virginia
city: Wauwatosa
country: United States
facility: Milwaukee Foot & Ankle Specialists
state: Wisconsin
Study officials:
affiliation: Celularity Incorporated
name: Solveig Ericson, MD
role: STUDY_DIRECTOR
References: