A Phase 1 Multicenter, Open-Label, Dose-Escalation Study to Evaluate the Safety and Efficacy of Intramuscular Injection of Human Placenta-Derived Cells (PDA-002) in Subjects With Peripheral Arterial Disease and Diabetic Foot Ulcer
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Peripheral Arterial Disease
- Sponsor
- Celularity Incorporated
- Enrollment
- 15
- Locations
- 11
- Primary Endpoint
- Maximum tolerated dose
- Status
- Completed
- Last Updated
- 8 years ago
Overview
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 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
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
- •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.
Exclusion Criteria
- •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.
Outcomes
Primary Outcomes
Maximum tolerated dose
Time Frame: 14 days of initial dosing
To determine the maximum tolerated dose (MTD) of PDA-002 administered intramuscularly (IM) in subjects with peripheral arterial disease (PAD) and DFU \[diabetic foot ulcer\].
Adverse Events
Time Frame: From signing informed consent until month 24
Number of participants with adverse events
Secondary Outcomes
- Toe-brachial index (TBI)(Approximately 2 years)
- Ankle-brachial index (ABI)(Approximately 2 years)