Back to resultsSafety and Efficacy Study of Thymosin Beta 4 in Patients With Acute Myocardial Infarction.Infarction
Primary Purpose
Acute Myocardial Infarction
Status
Completed
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Low Dose
Middle Dose
High Dose
Placebo
Sponsored by
About this trial
This is an interventional basic science trial for Acute Myocardial Infarction focused on measuring AMI
Eligibility Criteria
Inclusion Criteria:
- The subject or its legal representative will voluntarily participate in the study and sign the informed consent;
- Age 18 and 75, regardless of gender;
- STEMI patients with left anterior descending branch single-artery middle occlusion (TIMI grading 0~1, see Appendix 1 for TIMI grading) and receiving PCI;
- No obvious collateral of coronary artery (Rentrop grade 0~1,Rentrop grade see Appendix 2);
- Chest pain occurred for 6 hours and 12 hours before PCI;
- TIMI grade 3 after PCI;
- All subjects (male and female) must agree to use appropriate contraceptive methods (hormonal or barrier contraceptive methods, abstinence) during the study period and up to 6 months after the last administration, and women of childbearing age must test negative for pregnancy before administration.
Exclusion Criteria:
- Patients who have a history of myocardial infarction or have received coronary artery acute thrombolytic interventional therapy with bypass surgery;
- patients who received thrombolytic therapy after onset;
- patients who were clearly diagnosed as acute heart failure (Killip grade II,Killip classification in annex 3);
- Severe arrhythmia that cannot be corrected;
- Aortic dissection or suspected presence;
- Severe liver and kidney dysfunction or severe depletion, etc;
- major surgical history or hemorrhagic stroke in half a year;
- Has or has a history of malignancy;
- Systolic blood pressure ≥180 mmHg and/or diastolic blood pressure ≥110 mmHg in patients with hypertension after active antihypertensive treatment;
- Clinically, he had a significant history of allergy, especially to mannitol, drugs, protein preparations and biological products;
- Screening of patients who participated in other clinical studies within the first 3 months;
- Failure to perform CMR test: such as claustrophobia, renal failure (eGFR < 30ml/min);
- Other conditions not considered suitable for inclusion by the researcher.
Sites / Locations
- Fuwai Hospital, Chinese Academy of Medical Sciences
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
Low Dose
Middle Dose
High Dose
Placebo
Arm Description
Patients in this treatment group will receive NL005 for 0.25 ug/kg respective.Continuous administration for 7 days.
Patients in this treatment group will receive NL005 for 0.5 ug/kg respective.Continuous administration for 7 days.
Patients in this treatment group will receive NL005 for 2.0 ug/kg respective.Continuous administration for 7 days.
Patients in this treatment group will receive placebo respective. Continuous administration for 7 days.
Outcomes
Primary Outcome Measures
Change of myocardial infarction area on Day 5 and day 90 after PCI
Change of myocardial infarction area on Day 5 and day 90 after PCI. Myocardial infarction area day 5 and day 90 after PCI，and the change on day 90 compared to day 5. Myocardial infarction size was evaluated by late gadolinium enhanced cardiac magnetic resonance (LGE-CMR) imaging.
Secondary Outcome Measures
Change of myocardial salvage index on Day 5 and day 90 after PCI
Myocardial salvage index day 5 and day 90 after PCI，and the change on day 90 compared to day 5. Myocardial salvage index (%) defifined as: (area at risk-infarct size)/ area at risk*100% measured by CMR. Higher scores mean a better outcome.
Change of microvascular obstruction area on Day 5 and day 90 after PCI
Area of microvascular obstruction day 5 and day 90 after PCI，and the change on day 90 compared to day 5. Microvascular obstruction is one of the risk factors affecting the prognosis of AMI patients. The occurrence of MVO is related to the release of cytotoxic factors caused by distal microvascular embolization and reperfusion injury. Studies have shown a significantly increased risk of heart failure, adverse cardiovascular events, and death. late gadolinium enhancement (LGE) was performed to identify areas of microvascular obstruction (MVO), the typical MVO is the low signal area in the high signal area of infarction.
Change of LA on Day 5 and day 90 after PCI
Change of left atrium (LA) on Day 5 and day 90 after PCI, The data of LA after PCI were measured by CMR at Day 5 and day 90, and calculate changes in data day 90 and day 5.
Changeof LV on Day 5 and day 90 after PCI
Change of left ventricle (LV) on Day 5 and day 90 after PCI, Day 5 and day 90 LV after PCIwere measured by CMR at Day 5 and day 90, and calculate changes in data day 90 and day 5.
Change of LVEF on Day 5 and day 90 after PCI
Change of Left Ventricular Ejection Fractions (LVEF) on Day 5 and day 90 after PCI, Day 5 and day 90 LVEF after PCIwere measured by CMR at Day 5 and day 90, and calculate changes in data day 90 and day 5.
Change of LVESV on Day 5 and day 90 after PCI
Change of Left Ventricular end-systolic volume (LVESV) on Day 5 and day 90 after PCI, Day 5 and day 90 LVESV after PCI were measured by CMR at Day 5 and day 90, and calculate changes in data day 90 and day 5.
Change of LVEDV on Day 5 and day 90 after PCI
Change of Left Ventricular end-diastolic volume (LVEDV) on Day 5 and day 90 after PCI, Day 5 and day 90 LVEDV after PCI were measured by CMR at Day 5 and day 90, and calculate changes in data day 90 and day 5.
Number of participants with treatment-related adverse events as assessed by NCI-CTCAE v5.0
Number of participants with adverse events (AE), treatment-related adverse events, abnormal vital signs, abnormal physical examination findings, abnormal laboratory test results, abnormal electrocardiograms
Incidence of anti-drug antibody (ADA)
Blood samples were collected before administration and 30 days after PCI to evaluate the immunogenicity of NL005
Full Information
NCT ID
NCT05485818
First Posted
September 7, 2020
Last Updated
August 1, 2022
Sponsor
Beijing Northland Biotech. Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT05485818
Brief Title
Safety and Efficacy Study of Thymosin Beta 4 in Patients With Acute Myocardial Infarction.Infarction
Official Title
Phase IIa Clinical Study of Efficacy and Safety of Injectable Recombinant Human Thymosin Beta 4 in Patients With Acute Myocardial Infarction
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Completed
Study Start Date
November 23, 2020 (Actual)
Primary Completion Date
September 30, 2021 (Actual)
Study Completion Date
November 18, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Beijing Northland Biotech. Co., Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
A multicenter randomized double-blind placebo parallel control design was used in this study.60 subjects eligible for inclusion will be randomly assigned to either a low-dose (0.25ug/kg) medium-dose (0.5ug/kg) high-dose (2.0ug/kg) experimental drug group or a control group (placebo) at a ratio of 1:1:1:1.After randomization, subjects received the experimental drug or placebo once a day, intravenously, on day 2 to 7, 12 hours and 4 hours after PCI.Ninety days after PCI were observed.
Detailed Description
Subjects underwent cardiovascular magnetic resonance imaging (CMR) on the 90th day after PCI, which was used to evaluate the myocardial salvage index myocardial infarction area, microvascular occlusion area, left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and left ventricular end-diastolic volume (LVEDV).Echocardiography was performed on the 5th and the 90th day after PCI to evaluate the left indoor diameter (LV) and left atrial diameter (LA) of LVEF.
Physical examination routine blood coagulation function was performed on the 30th and 90th day after PCI in the screening period (pre-screening results were acceptable);Electrocardiogram (ECG) was performed on the 30th and the 90th day after PCI on the 2nd day after the first administration;During the screening period (results before screening are acceptable), vital signs should be measured from day 1 to day 7 after PCI (during each dose, vital signs should be measured twice on day 7, including before and after administration), on day 30 and day 90;Blood biochemical examinations were performed from day 2 to day 4, day 7, day 30, and day 90 after PCI before the first administration;Creatine kinase isoenzyme (CK-MB) hypersensitive troponin I(HS-CTNI) or troponin I(cTnI) and amino-terminal B-type natriuretic peptide precursor (NT-probNP) or B-type natriuretic peptide (BNP) were detected on day 2, day 3, day 4 and day 7 after PCI before the first administration.Tumor markers were detected and immunogenicity blood samples were collected 30 days after PCI before the first administration.Routine urinalysis was performed 90 days after PCI before the first administration;Adverse drug events and cardiovascular events were continuously recorded during the trial.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myocardial Infarction
Keywords
AMI
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
62 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Low Dose
Arm Type
Experimental
Arm Description
Patients in this treatment group will receive NL005 for 0.25 ug/kg respective.Continuous administration for 7 days.
Arm Title
Middle Dose
Arm Type
Experimental
Arm Description
Patients in this treatment group will receive NL005 for 0.5 ug/kg respective.Continuous administration for 7 days.
Arm Title
High Dose
Arm Type
Experimental
Arm Description
Patients in this treatment group will receive NL005 for 2.0 ug/kg respective.Continuous administration for 7 days.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Patients in this treatment group will receive placebo respective. Continuous administration for 7 days.
Intervention Type
Drug
Intervention Name(s)
Low Dose
Other Intervention Name(s)
NL005（ Low Dose）
Intervention Description
12±4 hours after PCI: 0.25 ug/kg Recombinant Human Thymosin β4 （intravenous injection），Day2-Day7 after PCI：0.25 ug/kg Recombinant Human Thymosin β4 （intravenous injection）
Intervention Type
Drug
Intervention Name(s)
Middle Dose
Other Intervention Name(s)
NL005（ Middle Dose）
Intervention Description
12±4 hours after PCI: 0.5 ug/kg Recombinant Human Thymosin β4 （intravenous injection），Day2-Day7 after PCI：0.5 ug/kg Recombinant Human Thymosin β4 （intravenous injection）
Intervention Type
Drug
Intervention Name(s)
High Dose
Other Intervention Name(s)
NL005（High Dose）
Intervention Description
12±4 hours after PCI: 2.0 ug/kg Recombinant Human Thymosin β4 （intravenous injection），Day2-Day7 after PCI：2.0 ug/kg Recombinant Human Thymosin β4 （intravenous injection）
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
15 subjects will be randomly assigned to the placebo for 7 days
Primary Outcome Measure Information:
Title
Change of myocardial infarction area on Day 5 and day 90 after PCI
Description
Change of myocardial infarction area on Day 5 and day 90 after PCI. Myocardial infarction area day 5 and day 90 after PCI，and the change on day 90 compared to day 5. Myocardial infarction size was evaluated by late gadolinium enhanced cardiac magnetic resonance (LGE-CMR) imaging.
Time Frame
Day 5、Day 90
Secondary Outcome Measure Information:
Title
Change of myocardial salvage index on Day 5 and day 90 after PCI
Description
Myocardial salvage index day 5 and day 90 after PCI，and the change on day 90 compared to day 5. Myocardial salvage index (%) defifined as: (area at risk-infarct size)/ area at risk*100% measured by CMR. Higher scores mean a better outcome.
Time Frame
Day 5、Day 90
Title
Change of microvascular obstruction area on Day 5 and day 90 after PCI
Description
Area of microvascular obstruction day 5 and day 90 after PCI，and the change on day 90 compared to day 5. Microvascular obstruction is one of the risk factors affecting the prognosis of AMI patients. The occurrence of MVO is related to the release of cytotoxic factors caused by distal microvascular embolization and reperfusion injury. Studies have shown a significantly increased risk of heart failure, adverse cardiovascular events, and death. late gadolinium enhancement (LGE) was performed to identify areas of microvascular obstruction (MVO), the typical MVO is the low signal area in the high signal area of infarction.
Time Frame
Day 5、Day 90
Title
Change of LA on Day 5 and day 90 after PCI
Description
Change of left atrium (LA) on Day 5 and day 90 after PCI, The data of LA after PCI were measured by CMR at Day 5 and day 90, and calculate changes in data day 90 and day 5.
Time Frame
Day 5、Day 90
Title
Changeof LV on Day 5 and day 90 after PCI
Description
Change of left ventricle (LV) on Day 5 and day 90 after PCI, Day 5 and day 90 LV after PCIwere measured by CMR at Day 5 and day 90, and calculate changes in data day 90 and day 5.
Time Frame
Day 5、Day 90
Title
Change of LVEF on Day 5 and day 90 after PCI
Description
Change of Left Ventricular Ejection Fractions (LVEF) on Day 5 and day 90 after PCI, Day 5 and day 90 LVEF after PCIwere measured by CMR at Day 5 and day 90, and calculate changes in data day 90 and day 5.
Time Frame
Day 5、Day 90
Title
Change of LVESV on Day 5 and day 90 after PCI
Description
Change of Left Ventricular end-systolic volume (LVESV) on Day 5 and day 90 after PCI, Day 5 and day 90 LVESV after PCI were measured by CMR at Day 5 and day 90, and calculate changes in data day 90 and day 5.
Time Frame
Day 5、Day 90
Title
Change of LVEDV on Day 5 and day 90 after PCI
Description
Change of Left Ventricular end-diastolic volume (LVEDV) on Day 5 and day 90 after PCI, Day 5 and day 90 LVEDV after PCI were measured by CMR at Day 5 and day 90, and calculate changes in data day 90 and day 5.
Time Frame
Day 5、Day 90
Title
Number of participants with treatment-related adverse events as assessed by NCI-CTCAE v5.0
Description
Number of participants with adverse events (AE), treatment-related adverse events, abnormal vital signs, abnormal physical examination findings, abnormal laboratory test results, abnormal electrocardiograms
Time Frame
Day0、Day1、Day2、Day3、Day4、Day5、Day6、Day7、Day30、Day90
Title
Incidence of anti-drug antibody (ADA)
Description
Blood samples were collected before administration and 30 days after PCI to evaluate the immunogenicity of NL005
Time Frame
Day 0、Day 30
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
The subject or its legal representative will voluntarily participate in the study and sign the informed consent;
Age 18 and 75, regardless of gender;
STEMI patients with left anterior descending branch single-artery middle occlusion (TIMI grading 0~1, see Appendix 1 for TIMI grading) and receiving PCI;
No obvious collateral of coronary artery (Rentrop grade 0~1,Rentrop grade see Appendix 2);
Chest pain occurred for 6 hours and 12 hours before PCI;
TIMI grade 3 after PCI;
All subjects (male and female) must agree to use appropriate contraceptive methods (hormonal or barrier contraceptive methods, abstinence) during the study period and up to 6 months after the last administration, and women of childbearing age must test negative for pregnancy before administration.
Exclusion Criteria:
Patients who have a history of myocardial infarction or have received coronary artery acute thrombolytic interventional therapy with bypass surgery;
patients who received thrombolytic therapy after onset;
patients who were clearly diagnosed as acute heart failure (Killip grade II,Killip classification in annex 3);
Severe arrhythmia that cannot be corrected;
Aortic dissection or suspected presence;
Severe liver and kidney dysfunction or severe depletion, etc;
major surgical history or hemorrhagic stroke in half a year;
Has or has a history of malignancy;
Systolic blood pressure ≥180 mmHg and/or diastolic blood pressure ≥110 mmHg in patients with hypertension after active antihypertensive treatment;
Clinically, he had a significant history of allergy, especially to mannitol, drugs, protein preparations and biological products;
Screening of patients who participated in other clinical studies within the first 3 months;
Failure to perform CMR test: such as claustrophobia, renal failure (eGFR < 30ml/min);
Other conditions not considered suitable for inclusion by the researcher.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
KeFei Dou
Organizational Affiliation
Chinese Academy of Medical Sciences, Fuwai Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fuwai Hospital, Chinese Academy of Medical Sciences
City
Beijing
Country
China
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
20937304
Citation
Limana F, Capogrossi MC, Germani A. The epicardium in cardiac repair: from the stem cell view. Pharmacol Ther. 2011 Jan;129(1):82-96. doi: 10.1016/j.pharmthera.2010.09.002. Epub 2010 Oct 19.
Results Reference
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PubMed Identifier
21952932
Citation
Wrigley BJ, Lip GY, Shantsila E. The role of monocytes and inflammation in the pathophysiology of heart failure. Eur J Heart Fail. 2011 Nov;13(11):1161-71. doi: 10.1093/eurjhf/hfr122. Epub 2011 Sep 27.
Results Reference
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PubMed Identifier
18537603
Citation
Gutierrez SH, Kuri MR, del Castillo ER. Cardiac role of the transcription factor NF-kappaB. Cardiovasc Hematol Disord Drug Targets. 2008 Jun;8(2):153-60. doi: 10.2174/187152908784533702.
Results Reference
background
PubMed Identifier
21527742
Citation
Gordon JW, Shaw JA, Kirshenbaum LA. Multiple facets of NF-kappaB in the heart: to be or not to NF-kappaB. Circ Res. 2011 Apr 29;108(9):1122-32. doi: 10.1161/CIRCRESAHA.110.226928.
Results Reference
background
PubMed Identifier
23050819
Citation
Srivastava D, Ieda M, Fu J, Qian L. Cardiac repair with thymosin beta4 and cardiac reprogramming factors. Ann N Y Acad Sci. 2012 Oct;1270:66-72. doi: 10.1111/j.1749-6632.2012.06696.x.
Results Reference
background
PubMed Identifier
22236126
Citation
Dube KN, Bollini S, Smart N, Riley PR. Thymosin beta4 protein therapy for cardiac repair. Curr Pharm Des. 2012;18(6):799-806. doi: 10.2174/138161212799277699.
Results Reference
result
Links:
URL
http://www.northland-bio.com/
Description
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Safety and Efficacy Study of Thymosin Beta 4 in Patients With Acute Myocardial Infarction.Infarction
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