Efficacy and Safety of Targeted Intramyocardial Delivery of Auto CD34+ Stem Cells for Improving Exercise Capacity in Subjects With Refractory Angina

NCT01508910 | Completed Phase 3 Results DMC

• 2 other identifiers: 901001RENEW Study
• Study Type: interventional
• Target: 291
• Locations: 1 country
• Sites: 41

Brief Summary

The purpose of the study is to assess the safety and efficacy of targeted intramyocardial delivery of Auto-CD34+ cells for increasing exercise time and amelioration of anginal symptoms in subjects with refractory angina and chronic myocardial ischemia.

Conditions

Chronic Myocardial Ischemia; Refractory Angina Pectoris; Advanced Coronary Heart Disease

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Total Exercise Time on Exercise Tolerance Test (ETT) Using the Modified Bruce Protocol

  Baseline (BL) is the average of the two total exercise times measured during the screening period.

  Baseline and 12 month visit

Secondary Outcomes (5)

• Angina Frequency (Episodes Per Week) at the 12 Month Follow-up Visit

  Baseline and 12 month visit

• Change From Baseline in Total Exercise Time on Exercise Tolerance Test (ETT) at the 6 Month Follow-up Visit

  Baseline and 6 month visit

• Angina Frequency (Episodes Per Week) at the 6 Month Follow-up Visit

  6 month visit

• Percentage of Participants With Incidences of MACE From Randomization Until the End of the 24 Month Follow-up Period

  From randomization until the end of the 24 month follow-up period

• Percentage of Participants With at Least One Serious Adverse Event (SAE) From Randomization Until the End of the 24 Month Follow-up Period

  From randomization until the end of the 24 month follow-up period

Study Arms (3)

Treatment Arm

EXPERIMENTAL

Targeted intramyocardial delivery of 1 x 10\^5 Auto-CD34+ cells after granulocyte-colony stimulating factor (G-CSF) mobilization and apheresis

Biological: Auto-CD34+ cells

Active Control Arm

PLACEBO COMPARATOR

Targeted intramyocardial delivery of placebo after G-CSF mobilization and apheresis

Biological: Placebo: Diluent used to suspend Auto-CD34+ cells

Unblinded Standard of Care (SOC) Arm

OTHER

No study-related procedures will be performed.

Other: Standard of care

Interventions

Auto-CD34+ cells BIOLOGICAL

10 intramyocardial injections of 0.2 mL per injection site of Auto-CD34+ cells

Treatment Arm

Placebo: Diluent used to suspend Auto-CD34+ cells BIOLOGICAL

10 intramyocardial injections of 0.2 mL per injection site of placebo

Active Control Arm

Standard of care OTHER

Standard of care for refractory angina

Unblinded Standard of Care (SOC) Arm

Eligibility Criteria

• Age: 21 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female participants who are 21 to 80 years of age at the time of signing the informed consent.
• Participants with Canadian Cardiovascular Society (CCS) class III or IV chronic refractory angina.
• Participants without control of their angina symptoms in spite of maximal tolerated doses of anti-angina drugs. Participants must be on optimal therapy for their angina and must have been on a stable anti-anginal medication regimen for at least 4 weeks before signing the informed consent form.
• Participants with obstructive coronary disease unsuitable for conventional revascularization due to unsuitable anatomy or comorbidity as determined at the site and confirmed by an independent adjudication committee.
• Participants must have evidence of inducible myocardial ischemia.
• Participants must experience angina episodes.
• Participants must be able to complete 2 exercise tolerance tests on the treadmill within 3 weeks of randomization.
• If female of childbearing potential, subject must not be pregnant and agree to employ adequate birth control measures for the duration of the study.

You may not qualify if:

• Cardiovascular hospitalization within 60 days prior to potential study enrollment. Participant has had a successful or partially successful coronary artery bypass graft (CABG) within 6 months or PCTA within 60 days of potential study enrollment.
• Participant has had a placement of a bi-ventricular pacemaker for cardiac resynchronization therapy (CRT) for heart failure within 180 days of potential study enrollment.
• Participant has documented stroke or transient ischemic attacks (TIAs) within 60 days of potential study enrollment.
• Participant has a history of moderate to severe aortic stenosis; or severe aortic insufficiency; or severe mitral stenosis; or severe mitral insufficiency.
• Participant has a prosthetic aortic valve or a mechanical mitral valve replacement.
• Participant has severe co-morbidity associated with a reduction in life expectancy to less than 3 years as a result of chronic medical illnesses.
• Participants with cancer are excluded with the following exceptions:
• Subjects with in-situ non-melanoma skin cancer or in-situ cervical cancer are not excluded.
• Participants that have been cancer free for \>= 5 years as determined by their oncologist are not excluded. Subjects with a prior history of stem cell transplant for cancer are excluded no matter how long they have been cancer-free.
• Participants with a history of leukemia or other bone marrow disease.
• Participant has sickle cell disease or sickle cell trait.
• Participants with proliferative retinopathy.
• Participants with Hb A1c \> 9%.
• Participant has platelet counts \>10% above the upper limit of normal (ULN) or platelet counts \< 70,000.
• Participant has a hematocrit \< 30% prior to potential study enrollment.

Sponsors & Collaborators

• Lisata Therapeutics, Inc.: lead

Study Sites (41)

Unknown Facility

Birmingham, Alabama, United States

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Gilbert, Arizona, United States

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Phoenix, Arizona, United States

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La Jolla, California, United States

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Los Angeles, California, United States

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Oxnard, California, United States

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San Diego, California, United States

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Stanford, California, United States

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Boynton Beach, Florida, United States

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Daytona Beach, Florida, United States

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Gainesville, Florida, United States

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Jacksonville, Florida, United States

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Miami, Florida, United States

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Orlando, Florida, United States

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Tampa, Florida, United States

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Atlanta, Georgia, United States

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Augusta, Georgia, United States

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Chicago, Illinois, United States

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Iowa City, Iowa, United States

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Louisville, Kentucky, United States

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New Orleans, Louisiana, United States

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Boston, Massachusetts, United States

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Saginaw, Michigan, United States

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Minneapolis, Minnesota, United States

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Rochester, Minnesota, United States

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Haddon Heights, New Jersey, United States

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Newark, New Jersey, United States

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New York, New York, United States

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Charlotte, North Carolina, United States

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Durham, North Carolina, United States

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Cincinnati, Ohio, United States

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Cleveland, Ohio, United States

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Philadelphia, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Germantown, Tennessee, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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Salt Lake City, Utah, United States

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Seattle, Washington, United States

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Madison, Wisconsin, United States

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Milwaukee, Wisconsin, United States

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Related Publications (2)

• Povsic TJ, Henry TD, Traverse JH, Fortuin FD, Schaer GL, Kereiakes DJ, Schatz RA, Zeiher AM, White CJ, Stewart DJ, Jolicoeur EM, Bass T, Henderson DA, Dignacco P, Gu Z, Al-Khalidi HR, Junge C, Nada A, Hunt AS, Losordo DW; RENEW Investigators. The RENEW Trial: Efficacy and Safety of Intramyocardial Autologous CD34(+) Cell Administration in Patients With Refractory Angina. JACC Cardiovasc Interv. 2016 Aug 8;9(15):1576-85. doi: 10.1016/j.jcin.2016.05.003.

  PMID: 27491607 DERIVED

• Povsic TJ, Junge C, Nada A, Schatz RA, Harrington RA, Davidson CJ, Fortuin FD, Kereiakes DJ, Mendelsohn FO, Sherman W, Schaer GL, White CJ, Stewart D, Story K, Losordo DW, Henry TD. A phase 3, randomized, double-blinded, active-controlled, unblinded standard of care study assessing the efficacy and safety of intramyocardial autologous CD34+ cell administration in patients with refractory angina: design of the RENEW study. Am Heart J. 2013 Jun;165(6):854-861.e2. doi: 10.1016/j.ahj.2013.03.003. Epub 2013 Apr 19.

  PMID: 23708155 DERIVED

MeSH Terms

Conditions

Angina Pectoris

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Limitations and Caveats

Study terminated early due to business considerations. Participants in Treatment or Active Control arms who did not have injection of target cells/placebo assigned to Not Injected Arm. Not included in efficacy analysis but in safety follow-up.

Results Point of Contact

• Title: Clinical Trial Registries and Results Disclosure
• Organization: Baxalta US Inc.

ClinicalTrialsDisclosure@baxalta.com

Study Officials

• Caladrius Study Director

  Caladrius Biosciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2012
• First Posted: January 12, 2012
• Study Start: April 1, 2012
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2015
• Last Updated: December 19, 2018
• Results First Posted: February 15, 2017

Record last verified: 2018-11

Locations

US (41)