Study of Human Placenta-derived Cells (PDA001) to Evaluate the Safety and Effectiveness for Patients With Ischemic Stroke

NCT01310114 | Terminated Phase 2 DMC

• 1 other identifier: CCT-PDA001-SK-001
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

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.

Conditions

Stroke, Acute; Middle Cerebral Artery Stroke; Posterior Cerebral Artery Stroke

Keywords

Human Placenta-Derived Cells; Stem cells; Stroke; PDA001; Celgene; cenplacel-L

Outcome Measures

Primary Outcomes (3)

• Safety (Type, frequency, severity and potential relationship to study drug of adverse events)

  A Treatment-emergent AE was any AE that began or worsened in grade after the start of study drug through 30 days after the last dose of study drug or end of study whichever is later. Treatment related toxicity was one considered by the investigator to be possibly, probably or definitely related to study drug. AEs were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 on the following scale: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life-threatening, Grade 5 = death. A serious adverse event (SAE) is any AE occurring at any dose that: results in death; is fatal or life-threatening; results in persistent or significant disability or incapacity; requires or prolongs in-patient hospitalization; is a congenital anomaly/birth defect in the offspring of a patient; and constitutes an important medical event.

  Up to 24 months

• Clinical response defined by a ≥ 1 point decrease from baseline in the Modified Rankin Scale (mRS) at Day 91 post treatment

  The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of participants who have suffered a stroke or other causes of neurological disability, and it has become the most widely used clinical outcome measure for stroke clinical trials. The scale runs from 0-6, running from perfect health without symptoms to death. 0 - No symptoms. 1 - No significant disability. Able to carry out all usual activities, despite some symptoms. 2 - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. 3 - Moderate disability. Requires some help, but able to walk unassisted. 4 - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted. 5 - Severe disability. Requires constant nursing care and attention, bedridden, incontinent. 6 - Dead.

  Baseline to 91 days

• Clinical response defined by a ≥ 1 point decrease from baseline in the Modified Rankin Scale (mRS) at Day 181 post treatment

  The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of participants who have suffered a stroke or other causes of neurological disability, and it has become the most widely used clinical outcome measure for stroke clinical trials. The scale runs from 0-6, running from perfect health without symptoms to death. 0 - No symptoms. 1 - No significant disability. Able to carry out all usual activities, despite some symptoms. 2 - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. 3 - Moderate disability. Requires some help, but able to walk unassisted. 4 - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted. 5 - Severe disability. Requires constant nursing care and attention, bedridden, incontinent. 6 - Dead.

  181 days

Secondary Outcomes (3)

• Clinical response defined by a ≥ 1 point decrease from baseline in the Modified Rankin Scale (mRS) at 24 months post treatment

  Up to 24 months

• Clinical response defined as a ≥ 4 point decrease from baseline in the National Institute of Health Stroke Scale (NIHSS)

  Up to 24 months

• Clinical response defined as a clinically significant improvement (at least 20-point increase from baseline) in the Barthel Index (BI)

  Up to 24 months

Study Arms (3)

Cohort 1

EXPERIMENTAL

1 unit PDA001 \[approximately 2 x 108 cells\] in 240 mL per infusion on Day 1.

Biological: Human Placenta-Derived Cells PDA001- (cenplacel-L)

Cohort 2A - Experimental

EXPERIMENTAL

1 unit PDA001 \[approximately 2 x 108 cells\] or placebo in 240 mL per infusion on Day 1

Biological: Human Placenta-Derived Cells PDA001- (cenplacel-L); Drug: Placebo

Cohort 2B - Experimental

EXPERIMENTAL

4 units PDA001 \[approximately 8 x 108 cells\] or placebo in 240 mL per infusion on Day 1

Biological: Human Placenta-Derived Cells PDA001- (cenplacel-L); Drug: Placebo

Interventions

Human Placenta-Derived Cells PDA001- (cenplacel-L) BIOLOGICAL

240 mL of intravenous infusion

Cohort 1; Cohort 2A - Experimental; Cohort 2B - Experimental

Placebo DRUG

Thawed placebo

Cohort 2A - Experimental; Cohort 2B - Experimental

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females 18 years of age to 80 years of age at the time of signing of the informed consent document.
• Subject or subject's legal representative must understand and voluntarily sign an informed consent document prior to any study-related assessments/procedures being conducted.
• Able to adhere to the study visit schedule and other protocol requirements.
• 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.
• 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.
• 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.
• 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.
• 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.

You may not qualify if:

• 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.
• Pregnant or lactating females.
• 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.
• 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.
• 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.
• 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.

Sponsors & Collaborators

• Celularity Incorporated: lead
• Celgene Corporation: collaborator

Study Sites (1)

Chattanooga Center for Neurologic Research

Chattanooga, Tennessee, 37403, United States

Location

MeSH Terms

Conditions

Stroke; Infarction, Middle Cerebral Artery; Infarction, Posterior Cerebral Artery

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Cerebral Infarction; Brain Infarction; Brain Ischemia; Cerebral Arterial Diseases; Intracranial Arterial Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Study Officials

• Monica E Luchi, MD

  Celularity Incorporated

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2011
• First Posted: March 8, 2011
• Study Start: March 1, 2011
• Primary Completion: March 1, 2013
• Study Completion: March 1, 2013
• Last Updated: March 1, 2018

Record last verified: 2016-03

Locations

US (1)