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

Sponsor

Celularity Incorporated (Industry)

Overall Status

Terminated

CT.gov ID

NCT02264288

Collaborator

(none)

159

Enrollment

Locations

Arms

40.2

Actual Duration (Months)

2.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Peripheral Arterial Disease Diabetic Foot	Biological: 3 x 10^6 cells Biological: 10 x 10^6 cells Biological: 30 x 10^6 cells Other: Placebo	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

159 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Oct 23, 2014

Actual Primary Completion Date :

Feb 28, 2018

Actual Study Completion Date :

Feb 28, 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

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

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)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cardiology PC	Birmingham	Alabama	United States	35211
2	TFi Medical	Mobile	Alabama	United States	36608
3	East Valley Foot and Ankle Specialist	Mesa	Arizona	United States	85206
4	Carl T. Hayden Veterans Affairs Medical Center	Phoenix	Arizona	United States	85012
5	Arizona Arthritis and Rheumatology Research, PLLC	Phoenix	Arizona	United States	85023
6	Aung Foothealth Clinics and Advanced Wound Care Center	Tucson	Arizona	United States	85710
7	Northeast Arkansas Baptist Clinic	Jonesboro	Arkansas	United States	72401
8	Jeffrey A Klemes DPM	Beverly Hills	California	United States	90211
9	Center for Clinical Research Inc.	Castro Valley	California	United States	94546-5306
10	Reliance Clinical Research	Chino	California	United States	91710
11	Limb Preservation Platform, INC.	Fresno	California	United States	93720
12	Foot and Ankle Clinic	Los Angeles	California	United States	90010
13	UCLA	Los Angeles	California	United States	90095
14	VA Palo Alto Health Care System	Palo Alto	California	United States	94304
15	Stanford University	Stanford	California	United States	94035-5821
16	Georgetown University Medical Center Lombardi Cancer Center	Washington	District of Columbia	United States	20007-2197
17	Clinical Research of West Florida Inc - Clearwater	Clearwater	Florida	United States	33765
18	Barry University	Fort Lauderdale	Florida	United States	33321
19	Florida Research Network, LLC	Gainesville	Florida	United States	32605
20	The Research Center	Hialeah	Florida	United States	33012
21	University of Florida	Jacksonville	Florida	United States	32209
22	Solutions Through Advanced Research Inc.	Jacksonville	Florida	United States	32258
23	GF Professional Research Group Corporation	Miami Lakes	Florida	United States	33016
24	University of Miami	Miami	Florida	United States	33136
25	Well Pharma Medical Research Corporation	Miami	Florida	United States	33143
26	Med-Care Research Inc	North Miami Beach	Florida	United States	33162
27	Podiatry 1st	Belleville	Illinois	United States	62226
28	University of Illinois at Chicago Cancer Center	Chicago	Illinois	United States	60612
29	Weill Foot & Ankle Institute	Des Plaines	Illinois	United States	60016
30	Rosalind Franklin University of Medicine and Science	North Chicago	Illinois	United States	60064
31	Southern Illinois University	Springfield	Illinois	United States	62702
32	Foot and Ankle Center of Illinois	Springfield	Illinois	United States	62704
33	CGH Medical Center Main Clinic	Sterling	Illinois	United States	61081
34	Hamilton Foot Care	Baltimore	Maryland	United States	21214
35	Sinai Hospital of Baltimore	Baltimore	Maryland	United States	21215
36	Northwest Hospital	Randallstown	Maryland	United States	21133
37	Revive Research Institute	Sterling Heights	Michigan	United States	48313
38	Englewood Hospital and Medical Center	Englewood	New Jersey	United States	07631
39	Office of Michael J. De Marco, DPM	Tinton Falls	New Jersey	United States	07724
40	Ocean City Foot and Ankle Assoc	Toms River	New Jersey	United States	08753
41	Animas Foot and Ankle	Gallup	New Mexico	United States	87301
42	Office of Gerard J. Furst, DPM, PLLC	East Setauket	New York	United States	11733
43	Syracuse VA Medical Center	Syracuse	New York	United States	13210
44	UNC Hospitals University of North Carolina	Chapel Hill	North Carolina	United States	27599-7010
45	Clinical Research Associates of Central Pennsylvania	Duncansville	Pennsylvania	United States	16635
46	University of Pennsylvania Health Systems	Philadelphia	Pennsylvania	United States	19104
47	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390-9068
48	Premier Vein and Vascular Center	Houston	Texas	United States	77084
49	Complete Family Foot Care - McAllen Office	McAllen	Texas	United States	78501-2930
50	Endeavor Clinical Trials PA	San Antonio	Texas	United States	78229
51	SAM Clinical Research Center	San Antonio	Texas	United States	78229
52	Advanced Foot & Ankle Center	Salt Lake City	Utah	United States	84102
53	Carilion Clinic	Roanoke	Virginia	United States	24013
54	1Foot 2Foot Centre for Foot & Ankle Care PC	Suffolk	Virginia	United States	23434
55	Milwaukee Foot & Ankle Specialists	Wauwatosa	Wisconsin	United States	53226