Study of Human Placenta-derived Cells (PDA002) to Evaluate the Safety and Effectiveness in Subjects With PAD and DFU

NCT ID: NCT01859117

Last Updated: 2018-03-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

15 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-05-31

Study Completion Date

2016-10-31

Brief Summary

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This clinical study is being conducted to assess the safety and determine the maximum tolerated dose (MTD) of PDA-002 \[human placenta-derived cells\] administered into the lower leg muscles of subjects with peripheral arterial disease and diabetic foot ulcers. It will look to see if PDA-002 helps reduce some of the symptoms of PAD and/or improves ulcer healing. This study will also help to find the best dose of PDA-002 to use in future studies.

Detailed Description

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The goal of this study is to determine a safe dose of PDA-002 \[human placenta-derived cells\] for further study. This is a dose-escalation study where each of four dose levels will enroll three to six subjects. Doses will be range from 3 million up to 100 million cells. If one dose is considered safe after all treated subjects have been evaluated and reviewed, then the next group of subjects will be enrolled to receive the next higher dose. This will continue until either the highest dose is reached, until at least 2 subjects at a dose level have ≥ Grade 2 allergic reaction that is suspected to be related to PDA-002 or 2 or more subjects at a dose level experience an unexpected, treatment-related serious adverse event or dose limiting toxicity within 14 days following the initial dose of PDA-002. This is an open-label study where all subjects will be taking the study drug and all study personnel will know the dose each subject receives.

Conditions

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Peripheral Arterial Disease Diabetic Foot

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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3 x 10^6 cells

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

Group Type EXPERIMENTAL

3 x 10^6 cells

Intervention Type BIOLOGICAL

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 intramuscularly on Study Days 1 and 8

Group Type EXPERIMENTAL

10 x 10^6 cells

Intervention Type BIOLOGICAL

10 x 10\^6 cells 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

Group Type EXPERIMENTAL

30 x 10^6 cells

Intervention Type BIOLOGICAL

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

100 x 10^6 cells

100 x 10\^6 Human Placenta Derived cells (PDA-002) administered intramuscularly on Study Days 1 and 8

Group Type EXPERIMENTAL

100 x 10^6 cells

Intervention Type BIOLOGICAL

100 x 10\^6 cells administered on Study Days 1 and 8

Interventions

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3 x 10^6 cells

3 x 10\^6 cells administered on Study Days 1 and 8

Intervention Type BIOLOGICAL

10 x 10^6 cells

10 x 10\^6 cells administered on Study Days 1 and 8

Intervention Type BIOLOGICAL

30 x 10^6 cells

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

Intervention Type BIOLOGICAL

100 x 10^6 cells

100 x 10\^6 cells administered on Study Days 1 and 8

Intervention Type BIOLOGICAL

Other Intervention Names

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PDA-002 PDA-002 PDA-002 PDA-002

Eligibility Criteria

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Inclusion Criteria

* Subjects must satisfy the following criteria to be enrolled in the study:

1. Males and females, 18 to 80 years of age 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 2
5. Ischemic or neuro-ischemic 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.
6. Peripheral arterial disease with ankle-brachial index \> 0.6 and ≤ 0.9 or toe-brachial index \> 0.35 and ≤ 0.7.
7. No planned revascularization or amputation over the next 3 months after Screening visit, in the opinion of the Investigator.
8. Not a candidate for peripheral artery percutaneous or surgical revascularization.
9. Screening should not begin until at least 2 weeks after a failed reperfusion intervention and at least 2 months after a successful mechanical intervention.
10. Subject can have stable angina, (Canadian Cardiovascular Society (CCS) Class I-II angina (Appendix H).
11. Subjects should be receiving appropriate medical therapy for hypertension and diabetes.
12. Subject must be a non-tobacco user defined as someone who has not used tobacco/nicotine patch for ≥ 3 months and must agree to remain tobacco/nicotine free for the duration of the study.
13. A female of childbearing potential \[FCBP\] 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; intrauterine device \[IUD\]; barrier contraceptive with spermicide or vasectomized partner for the duration of the study and the follow-up period.
14. 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

* The presence of any of the following will exclude a subject from enrollment:

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. Subjects whom, in the judgment of the Investigator, are at elevated risk for the development of a malignancy. This judgment may be based on family history, history of industrial exposures, smoking history or other cancer risk factors.
5. Known to be positive for human immunodeficiency virus.
6. Pregnant or lactating females.
7. Subjects with a body mass index \> 35 at Screening.
8. Aspartate transaminase (AST) or Alanine transaminase (ALT) \> 2.5 x the upper limit of normal (ULN) at Screening.
9. Estimated Glomerular Filtration Rate (eGFR) \< 45 mL/min/1.73 m2 at Screening calculated using the Modification of Diet in Renal Disease Study equation (Levey, 2006) or history of eGFR decline \> 15 mL/min/1.73 m2 in the past year.
10. Alkaline phosphatase \> 2.5 x the ULN at Screening.
11. Bilirubin level \> 2 mg/dL (unless subject has known Gilbert's disease) at Screening.
12. Untreated chronic infection or treatment of any infection with systemic antibiotics, including the ulcer site, within 4 weeks prior to dosing with investigational product \[IP\].
13. Known osteomyelitis.
14. History of Methicillin-resistant Staphylococcus aureus (MRSA).
15. Ulcer that has decreased or increased in size by ≥ 50% during the screening period.
16. 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).
17. Poorly controlled diabetes mellitus (hemoglobin A1c \> 9%).
18. Untreated proliferative retinopathy.
19. History of malignant ventricular arrhythmia, CCS Class III-IV angina pectoris, myocardial infarction/PCI (percutaneous coronary intervention)/CABG (coronary artery bypass graft) in the preceding 6 months, pending coronary revascularization in the following 2 months, transient ischemic attack/cerebrovascular accident in the preceding 6 months, and/or New York Heart Association \[NYHA\] Stage III or IV congestive heart failure, (Appendix C).
20. Abnormal ECG: new bundle branch block (BBB) ≥ 120 msec in the preceding 3 months; QTcB and/or QTcF \> 480 msec or QTcB and/or QTcF ≥ 500 msec with old BBB. Patients with a potential risk for Torsades des Pointes should not be enrolled.
21. Uncontrolled hypercoagulation.
22. Life expectancy less than 2 years due to concomitant illnesses.
23. In the opinion of the Investigator, the subject is unsuitable for cellular therapy.
24. History of malignancy within 5 years 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.
25. History of hypersensitivity to any of the components of the product formulation (including bovine or porcine products, dextran 40, and dimethyl sulfoxide \[DMSO\]).
26. Disorders or allergies precluding the use of radiographic contrast or renal insufficiency severe enough to contraindicate the use of radiographic contrast.
27. 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.
28. Subject has received previous gene or cell therapy.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Celularity Incorporated

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Monica E Luchi, MD

Role: STUDY_DIRECTOR

Celularity Incorporated

Locations

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Carl T. Hayden Veterans Affairs Medical Center

Phoenix, Arizona, United States

Site Status

UCLA

Los Angeles, California, United States

Site Status

Stanford University School of Medicine

Stanford, California, United States

Site Status

Dr. Wiliam M. Scholl College of Podiatric Medicine

North Chicago, Illinois, United States

Site Status

Southern Illinois University School of Medicine

Springfield, Illinois, United States

Site Status

University of North Carolina School of Medicine

Chapel Hill, North Carolina, United States

Site Status

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

Complete Family Foot Care - McAllen Office

McAllen, Texas, United States

Site Status

Endeavor Clinical Trials PA

San Antonio, Texas, United States

Site Status

University of Virginia

Charlottesville, Virginia, United States

Site Status

University of Wisconsin

Madison, Wisconsin, United States

Site Status

Countries

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United States

References

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Francki A, Labazzo K, He S, Baum EZ, Abbot SE, Herzberg U, Hofgartner W, Hariri R; Celgene Cellular Therapeutics Research Group. Angiogenic properties of human placenta-derived adherent cells and efficacy in hindlimb ischemia. J Vasc Surg. 2016 Sep;64(3):746-756.e1. doi: 10.1016/j.jvs.2015.04.387. Epub 2015 Jun 6.

Reference Type DERIVED
PMID: 26054585 (View on PubMed)

Other Identifiers

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CCT-PDA-002-DFU-001

Identifier Type: -

Identifier Source: org_study_id

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