Study of ALD-401 Via Intracarotid Infusion in Ischemic Stroke Subjects

NCT01273337 | Unknown Phase 2 DMC

• 1 other identifier: IS-001
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 9

Brief Summary

The purpose of this study is to demonstrate the safety of the delivery of ALD-401 by intracarotid infusion and to assess efficacy of treatment in subjects who have had unilateral, predominately cortical, ischemic strokes in the middle cerebral artery (MCA). ALD-401 is made from the stroke patient's bone marrow and infused 13-19 days after the stroke.

Conditions

Stroke; Ischemic Stroke; Stroke in Middle Cerebral Artery (MCA)

Keywords

Stroke; Ischemia; Ischemic Stroke; Middle Cerebral Artery; MCA; Stem Cells; Stem Cell; Autologous Bone Marrow; Ipsilateral MCA

Outcome Measures

Primary Outcomes (1)

• Safety of Delivery of ALD-401

  The safety of the delivery of ALD-401 will be assessed by the following: * Frequency and proportion of severe adverse events, * Physical and clinical laboratory testing, * Radiological worsening as detected by MRI (evidence of hemorrhage) with and without clinical symptoms, * MRI evidence of new heterotopias, tumors, or vascular malformations over 12 months * Increase of NIHSS by ≥ 4 pts within 24 h of injection, * Re-hospitalization, * Survival.

  1 year

Secondary Outcomes (1)

• Efficacy of recovery of Mental and Physical Function

  1 year

Study Arms (2)

ALD-401

EXPERIMENTAL

ALD-401 is derived from Autologous Bone Marrow of the Stroke Subject

Biological: ALD-401

Sham Comparitor

SHAM COMPARATOR

Sham Bone Marrow harvest and sham dosing procedure.

Procedure: Sham Procedure

Interventions

ALD-401 BIOLOGICAL

3 mL ALDHbr cells isolated from autologous bone marrow given as a one-time infusion via intracarotid infusion.

Also known as: ALDHbr cells, ALDH Bright cells

ALD-401

Sham Procedure PROCEDURE

Sham bone marrow harvest and sham product infusion procedures.

Sham Comparitor

Eligibility Criteria

• Age: 30 Years - 83 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Is age 30 to 83 years,
• Has recent acute ischemic stroke in the middle cerebral artery (MCA) distribution confirmed by MRI or CT scan, with known onset time (within 24 hr),
• Has persistent neurological deficit (NIHSS ≤22), mRS ≥ 3 at randomization,
• Is able to provide bone marrow sample from anterior or posterior iliac crest at the time required by targeted infusion date,
• Is able to return for dosing two days post bone marrow harvest (day 13-19 post stroke) and remain overnight for observation,
• Is able to undergo (no contraindications) catheterization for localizing arteriograms for intracarotid/MCA delivery,
• Has patency of the carotid artery on the affected side demonstrated at screening and prior to infusion; and flow is established in the proximal branches (M1 and M2) of the affected carotid if the stroke is cortical. Occlusion of either the M1 or M2 can be included in the study if imaging prior to harvest demonstrates flow through collateral circulation to the area of the infarct. If the infarction is lacunar, the proximal MCA must be patent,
• Subjects who received tPA or underwent mechanical reperfusion may be included in the study as long as flow is established either in the proximal branches (M1 and M2) of the affected carotid or in the collateral circulation to the area of the infarct,
• Has a general state that is compatible with a program of functional rehabilitation, and is receiving standard of care as determined by the investigator,
• Is able to provide consent to study or informed consent is obtained from the subject's next of kin or legal representative,
• Females must be postmenopausal, surgically sterilized, or practicing a suitable method of birth control so that, in the opinion of the investigator, they will not become pregnant during the course of the study,
• Is a good candidate for the trial, in the opinion of the investigator.

You may not qualify if:

• Medical Conditions:
• Has a medical history of neurological or orthopedic pathology with deficit as a consequence that results in a modified Rankin Scale score \>1 before stroke) or has a cognitive deficit,
• Has a severe, persistent neurological deficit (NIHSS \>22), OR a change of ≥4 points in the NIHSS from screening (after 7 days) to randomization (3-4 days after screening),
• Has any clinically significant hemorrhagic (HI1 or PH1 petechial hemorrhages are allowed), or traumatic lesion of the brain on MRI or CT,
• Has stroke affecting the sub cortical area only,
• Has \>50% stenosis or ulcerated plaque in the carotid artery on the ipsilateral side and carotid endarterectomy or arterial stenting is recommended for treatment,
• Has had a seizure in the past 6 months (including associated with stroke),
• Has a serious psychiatric disease which could alter evaluation on functional or cognitive scales,
• Has a serious neurologic disease (e.g., multiple sclerosis, ALS) which could alter evaluation on functional or cognitive scales,
• Had a myocardial infarction in the past 3 months,
• Has a mechanical heart valve,
• Has known hepatic failure (Child-Pugh score Class B or C),
• Has an active systemic infection,
• Has an active malignancy or diagnosis of malignancy within 5 years prior to the start of screening (excluding skin cancers other than melanoma) or any history of chemotherapy or radiation affecting the bone marrow,
• Has a history of inflammatory or progressively fibrotic conditions (e.g., rheumatoid arthritis, systemic lupus erythematosis, vasculitic disorders, idiopathic pulmonary fibrosis, retroperitoneal fibrosis),

Sponsors & Collaborators

• Aldagen: lead

Study Sites (9)

Los Angeles Brain and Spine Institute

Los Angeles, California, 90027, United States

Location

University of Miami Hospital

Miami, Florida, 33136, United States

Location

Minneapolis Heart Institute

Minneapolis, Minnesota, 55407, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Ohio Health Research Institute

Columbus, Ohio, 43214, United States

Location

University of Pittsburgh Medical Center Presbyterian Hospital

Pittsburgh, Pennsylvania, 15213, United States

Location

University Medical Center at Brackenridge

Austin, Texas, 78701, United States

Location

The University of Texas Medical School

Houston, Texas, 77030, United States

Location

Swedish Medical Center, Cherry Hill Campus

Seattle, Washington, 98122, United States

Location

Related Publications (1)

• Savitz SI, Yavagal D, Rappard G, Likosky W, Rutledge N, Graffagnino C, Alderazi Y, Elder JA, Chen PR, Budzik RF Jr, Tarrel R, Huang DY, Hinson JM Jr. A Phase 2 Randomized, Sham-Controlled Trial of Internal Carotid Artery Infusion of Autologous Bone Marrow-Derived ALD-401 Cells in Patients With Recent Stable Ischemic Stroke (RECOVER-Stroke). Circulation. 2019 Jan 8;139(2):192-205. doi: 10.1161/CIRCULATIONAHA.117.030659.

  PMID: 30586746 DERIVED

MeSH Terms

Conditions

Stroke; Ischemic Stroke; Ischemia

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• James M Hinson, MD

  Aldagen

  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: January 6, 2011
• First Posted: January 10, 2011
• Study Start: March 1, 2011
• Primary Completion: July 1, 2014
• Study Completion: January 1, 2015
• Last Updated: January 16, 2014

Record last verified: 2014-01

Locations

US (9)