Clinical trial NCT01310114: Study of Human Placenta-derived Cells (PDA001) to Evaluate the Safety and Effectiveness for Patients With Ischemic Stroke
Official title: A Phase 2A, Prospective, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study to Evaluate the Safety of Intravenous Infusion of Human Placenta-Derived Cells (PDA001) for the Treatment of Adults Following Ischemic Stroke
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Stroke, Acute
Middle Cerebral Artery Stroke
Posterior Cerebral Artery Stroke
Keywords: Human Placenta-Derived Cells
Stem cells
Stroke
PDA001
Celgene
cenplacel-L
Lead sponsor: Celularity Incorporated
Sponsor class: INDUSTRY
Collaborators: name: Celgene Corporation
First posted: 2011-03-08
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of the study is to assess the safety and tolerability of Human Placenta-Derived Cells (PDA001) at 3 different dose levels versus placebo (vehicle control) administered intravenously in subjects following ischemic stroke. The secondary objective of the study is to assess the effect of PDA001 on improvement in clinical function following ischemic stroke.


Eligibility criteria: Inclusion Criteria

1. Males and females 18 years of age to 80 years of age at the time of signing of the informed consent document.
2. Subject or subject's legal representative must understand and voluntarily sign an informed consent document prior to any study-related assessments/procedures being conducted.
3. Able to adhere to the study visit schedule and other protocol requirements.
4. A female of childbearing potential (FCBP) must have a negative serum or urine pregnancy test within 48 ± 24 hours prior to treatment with study therapy. In addition, sexually active FCBP must agree to use two of the following adequate forms of contraception methods simultaneously such as: oral, injectable or implantable hormonal contraception; tubal ligation; intrauterine device; 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.
5. Diagnosis of stroke involving the middle cerebral artery (MCA) territory (cortical and subcortical) or posterior cerebral artery (PCA) (PCA is limited to 3 subjects per cohort) ischemic stroke confirmed by magnetic resonance imaging (MRI)/ computerized tomography (CT). An ischemic stroke is death of an area of brain tissue (cerebral infarction) resulting from an inadequate supply of blood and oxygen to the brain.
6. National Institute of Health Stroke Scale (NIHSS) score of ≥ 6 but \< 20 at the time of screening and infusion. Subject should not have shown rapid improvement (≥ 8 point decrease) or deterioration (≥ 4 point increase) in the score from time of initial evaluation to pre-infusion. To the extent possible, the time from initial screening evaluation to reevaluation will be at least 24 hours.
7. Subject must have had a normal neurologic status prior to ischemic episode defined as the absence of focal or global central neurological or psychiatric deficits of sufficient magnitude that it could not reasonably be expected that the subject could recover to the normal range based on the instruments used to assess the subject's response to treatment. The pre-stroke modified Rankin score should be between 0 and 2 inclusive.
8. Treatment with tissue plasminogen activator (tPA) or Food and Drug Administration (FDA)-approved devices used to restore circulation are allowed but treatment must be completed at least 24 hours prior to administration of PDA001.

Exclusion Criteria

1. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject or subject's legal representative from signing the informed consent form.
2. Pregnant or lactating females.
3. Any condition, including any medical or neuropsychiatric condition, including the presence of laboratory abnormalities, which in the judgment of the investigator places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study including (but not limited to):

   * Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT ) \> 2.5 x the upper limit of normal at screening.
   * Serum creatinine concentration \>1.5 times the upper limit of normal at screening.
   * Bilirubin or alkaline phosphatase level \> 2.5 x the upper limit of normal at screening.
   * Glucose \< 50 mg/dL or \> 250 mg/dL despite adequate antihyperglycemic treatment.
   * Platelet count \< 100 x 109 per liter.
   * History of bacteremia or other serious bacterial or fungal infection requiring treatment with IV antibiotics within 84 days (12 weeks) prior to treatment with study therapy other than a treated urinary tract infection.
   * Known infection with human immunodeficiency virus (HIV).
   * Seropositive for hepatitis C or hepatitis B.
   * Known history of seizures.
4. Severe heart failure or evidence of acute myocardial infarction defined of having at least two of the following three features: (1) Chest pain suggestive of cardiac ischemia; (2)Electrocardiogram (ECG) findings of ST elevation of greater than 0.2 mV in 2 contiguous leads, new onset left bundle branch block, ST segment depression, or T-wave inversion; (3) Elevated troponin I. History of prior myocardial infarction within the previous 6 months.
5. Evidence of prior cerebral hemorrhage or ischemic stroke within the last 3 months or recent intracerebral hematomas by head CT or MRI. This exclusion does not include clinically insignificant petechial hemorrhages.
6. Subjects with only lacunar infarcts on MRI or CT. A lacunar infarct is defined as a small (0.2 to 15 mm in diameter) noncortical infarct caused by occlusion of a single penetrating branch of a large cerebral artery.
7. Persistent hypertension with systolic blood pressure (BP) greater than 185 mmHg or diastolic BP greater than 110 mmHg (mean of 3 consecutive arm cuff readings over 20-30 minutes), not controlled by antihypertensive therapy or requiring nitroprusside for control. Efforts should be made to bring systolic blood pressure (BP) to ≤ 160 or diastolic BP ≤ 100 mmHg at the time of IP administration.
8. Clinically significant pulmonary dysfunction, including severe chronic obstructive pulmonary disease (COPD) and history of lung resection.
9. High clinical suspicion of septic embolus.
10. History of pulmonary emboli or deep vein thrombus
11. History of major trauma at time of stroke
12. 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.
13. Known allergy to bovine or porcine products.
14. Known allergy to both gadolinium and iodine based contrast agents for MRI or CT scan preventing the ability to conduct either one of these procedures.
15. Subject has received an investigational agent -an agent or device not approved by 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 trial prior to the completion of this study.

Primary outcomes:
measure: Safety (Type, frequency, severity and potential relationship to study drug of adverse events)
timeFrame: Up to 24 months
measure: Clinical response defined by a ≥ 1 point decrease from baseline in the Modified Rankin Scale (mRS) at Day 91 post treatment
timeFrame: Baseline to 91 days
measure: Clinical response defined by a ≥ 1 point decrease from baseline in the Modified Rankin Scale (mRS) at Day 181 post treatment
timeFrame: 181 days
Secondary outcomes:
measure: Clinical response defined by a ≥ 1 point decrease from baseline in the Modified Rankin Scale (mRS) at 24 months post treatment
timeFrame: Up to 24 months
measure: Clinical response defined as a ≥ 4 point decrease from baseline in the National Institute of Health Stroke Scale (NIHSS)
timeFrame: Up to 24 months
measure: Clinical response defined as a clinically significant improvement (at least 20-point increase from baseline) in the Barthel Index (BI)
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Chattanooga
country: United States
facility: Chattanooga Center for Neurologic Research
state: Tennessee
Study officials:
affiliation: Celularity Incorporated
name: Monica E Luchi, MD
role: STUDY_DIRECTOR
References: