Status:
COMPLETED
Study of Human Placenta-derived Cells (PDA002) to Evaluate the Safety and Effectiveness in Subjects With PAD and DFU
Lead Sponsor:
Celularity Incorporated
Conditions:
Peripheral Arterial Disease
Diabetic Foot
Eligibility:
All Genders
18-80 years
Phase:
PHASE1
Brief Summary
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 subjec...
Detailed Description
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 si...
Eligibility Criteria
Inclusion
- Subjects must satisfy the following criteria to be enrolled in the study:
- Males and females, 18 to 80 years of age 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 2
- 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.
- Peripheral arterial disease with ankle-brachial index \> 0.6 and ≤ 0.9 or toe-brachial index \> 0.35 and ≤ 0.7.
- No planned revascularization or amputation over the next 3 months after Screening visit, in the opinion of the Investigator.
- Not a candidate for peripheral artery percutaneous or surgical revascularization.
- Screening should not begin until at least 2 weeks after a failed reperfusion intervention and at least 2 months after a successful mechanical intervention.
- Subject can have stable angina, (Canadian Cardiovascular Society (CCS) Class I-II angina (Appendix H).
- Subjects should be receiving appropriate medical therapy for hypertension and diabetes.
- 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.
- 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.
- 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
- The presence of any of the following will exclude a subject from enrollment:
- 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.
- 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.
- Known to be positive for human immunodeficiency virus.
- Pregnant or lactating females.
- Subjects with a body mass index \> 35 at Screening.
- Aspartate transaminase (AST) or Alanine transaminase (ALT) \> 2.5 x the upper limit of normal (ULN) at Screening.
- 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.
- Alkaline phosphatase \> 2.5 x the ULN at Screening.
- 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, within 4 weeks prior to dosing with investigational product \[IP\].
- Known osteomyelitis.
- History of Methicillin-resistant Staphylococcus aureus (MRSA).
- Ulcer that has decreased or increased in size by ≥ 50% during the screening period.
- 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 \> 9%).
- Untreated proliferative retinopathy.
- 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).
- 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.
- Uncontrolled hypercoagulation.
- Life expectancy less than 2 years due to concomitant illnesses.
- In the opinion of the Investigator, the subject is unsuitable for cellular therapy.
- 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.
- History of hypersensitivity to any of the components of the product formulation (including bovine or porcine products, dextran 40, and dimethyl sulfoxide \[DMSO\]).
- Disorders or allergies precluding the use of radiographic contrast or renal insufficiency severe enough to contraindicate the use of radiographic contrast.
- 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 gene or cell therapy.
Key Trial Info
Start Date :
May 1 2013
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
October 1 2016
Estimated Enrollment :
15 Patients enrolled
Trial Details
Trial ID
NCT01859117
Start Date
May 1 2013
End Date
October 1 2016
Last Update
March 1 2018
Active Locations (11)
Enter a location and click search to find clinical trials sorted by distance.
1
Carl T. Hayden Veterans Affairs Medical Center
Phoenix, Arizona, United States, 85012
2
UCLA
Los Angeles, California, United States, 90095
3
Stanford University School of Medicine
Stanford, California, United States, 94305-5317
4
Dr. Wiliam M. Scholl College of Podiatric Medicine
North Chicago, Illinois, United States, 60064