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

Peripheral Arterial Disease Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02264288
• Other study ID #: CCT-PDA-002-DFU-002
• Status: Terminated
• Phase: Phase 2
• Start date: October 23, 2014
• Est. completion date: February 28, 2018

Study information

• Verified date: February 2019
• Source: Celularity Incorporated
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 159
• Est. completion date: February 28, 2018
• Est. primary completion date: February 28, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diabetic Foot
• Foot Ulcer
• Peripheral Arterial Disease
• Peripheral Vascular Diseases

Intervention

Biological:
• 3 x 10^6 cells
3 x 10^6 cells administered on Study Days 1 and 8
• 10 x 10^6 cells
10 x 10^6 Human Placenta Derived cells (PDA-002) administered on Study Days 1 and 8
• 30 x 10^6 cells
30 x 10^6 Human Placenta Derived cells (PDA-002) administered intramuscularly on Study Days 1 and 8

Other:
• Placebo
Identical matching placebo administered IM on Study Days 1 and 8

Locations

Country	Name	City	State
United States	Hamilton Foot Care	Baltimore	Maryland
United States	Sinai Hospital of Baltimore	Baltimore	Maryland
United States	Podiatry 1st	Belleville	Illinois
United States	Jeffrey A Klemes DPM	Beverly Hills	California
United States	Cardiology PC	Birmingham	Alabama
United States	Center for Clinical Research Inc.	Castro Valley	California
United States	UNC Hospitals University of North Carolina	Chapel Hill	North Carolina
United States	University of Illinois at Chicago Cancer Center	Chicago	Illinois
United States	Reliance Clinical Research	Chino	California
United States	Clinical Research of West Florida Inc - Clearwater	Clearwater	Florida
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Weill Foot & Ankle Institute	Des Plaines	Illinois
United States	Clinical Research Associates of Central Pennsylvania	Duncansville	Pennsylvania
United States	Office of Gerard J. Furst, DPM, PLLC	East Setauket	New York
United States	Englewood Hospital and Medical Center	Englewood	New Jersey
United States	Barry University	Fort Lauderdale	Florida
United States	Limb Preservation Platform, INC.	Fresno	California
United States	Florida Research Network, LLC	Gainesville	Florida
United States	Animas Foot and Ankle	Gallup	New Mexico
United States	The Research Center	Hialeah	Florida
United States	Premier Vein and Vascular Center	Houston	Texas
United States	Solutions Through Advanced Research Inc.	Jacksonville	Florida
United States	University of Florida	Jacksonville	Florida
United States	Northeast Arkansas Baptist Clinic	Jonesboro	Arkansas
United States	Foot and Ankle Clinic	Los Angeles	California
United States	UCLA	Los Angeles	California
United States	Complete Family Foot Care - McAllen Office	McAllen	Texas
United States	East Valley Foot and Ankle Specialist	Mesa	Arizona
United States	University of Miami	Miami	Florida
United States	Well Pharma Medical Research Corporation	Miami	Florida
United States	GF Professional Research Group Corporation	Miami Lakes	Florida
United States	TFi Medical	Mobile	Alabama
United States	Rosalind Franklin University of Medicine and Science	North Chicago	Illinois
United States	Med-Care Research Inc	North Miami Beach	Florida
United States	VA Palo Alto Health Care System	Palo Alto	California
United States	University of Pennsylvania Health Systems	Philadelphia	Pennsylvania
United States	Arizona Arthritis and Rheumatology Research, PLLC	Phoenix	Arizona
United States	Carl T. Hayden Veterans Affairs Medical Center	Phoenix	Arizona
United States	Northwest Hospital	Randallstown	Maryland
United States	Carilion Clinic	Roanoke	Virginia
United States	Advanced Foot & Ankle Center	Salt Lake City	Utah
United States	Endeavor Clinical Trials PA	San Antonio	Texas
United States	SAM Clinical Research Center	San Antonio	Texas
United States	Foot and Ankle Center of Illinois	Springfield	Illinois
United States	Southern Illinois University	Springfield	Illinois
United States	Stanford University	Stanford	California
United States	CGH Medical Center Main Clinic	Sterling	Illinois
United States	Revive Research Institute	Sterling Heights	Michigan
United States	1Foot 2Foot Centre for Foot & Ankle Care PC	Suffolk	Virginia
United States	Syracuse VA Medical Center	Syracuse	New York
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	Aung Foothealth Clinics and Advanced Wound Care Center	Tucson	Arizona
United States	Georgetown University Medical Center Lombardi Cancer Center	Washington	District of Columbia
United States	Milwaukee Foot & Ankle Specialists	Wauwatosa	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
Celularity Incorporated

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Time to ulcer closure	The time period for the index ulcer to close	Up to 6 months
Secondary	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
Secondary	50% Closure of Index Ulcer	The proportion of subjects with at least 50% closure of the index ulcer	Up to 24 months
Secondary	Transcutaneous oxygen	Transcutaneous oxygen measurements determine the oxygen level in tissue below the skin	Up to 6 months
Secondary	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
Secondary	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
Secondary	Rutherford Criteria	The Rutherford classification is a clinical staging system for describing peripheral arterial disease.	Up to 6 months
Secondary	36-item Short Form Health Survey (SF-36)	A validated measurement of health related quality of life	Up to 6 months
Secondary	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
Secondary	Patient Global Impression of Change in Neuropathy (PGICN)	Assessment of changes in neuropathy over time	Up to 24 months
Secondary	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
Secondary	Number of all ulcers	The total number of ulcers	Up to 24 months
Secondary	Leg rest pain score	A visual analog scale (VAS) graded from 0 (pain free) to Grade 10 (maximum pain)	Up to 24 months