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The goal of this phase IIc clinical trial is to learn if recombinant human thymosin beta 4 injection (NL005) works to treat heart damage in people who have had a serious type of heart attack called ST-segment elevation myocardial infarction (STEMI) and have been treated with emergency percutaneous coronary intervention (PCI, a procedure to open the blocked artery). It will also learn about the safety of NL005. The main questions it aims to answer are:
Researchers will compare two different doses of NL005 to a placebo (a look-alike substance that contains no drug) to see if NL005 works better to reduce heart damage caused by the heart attack.
Participants will:
This multicenter, randomized, double-blind, placebo-controlled, parallel-group phase IIc study evaluates the efficacy, safety, and pharmacokinetics of recombinant human thymosin beta 4 injection (NL005) in patients with acute STEMI undergoing primary PCI. Approximately 189 participants are randomized 1:1:1 to NL005 10 µg/kg, NL005 20 µg/kg, or matching placebo.
Eligible participants have first anterior STEMI from left anterior descending artery occlusion. Full eligibility details are provided in the corresponding module.
The study includes a screening period, a 7-day inpatient treatment phase, follow-up visits at Day 30 and Day 90, and an extended follow-up period through Day 360.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| NL005 10 µg/kg Group | Experimental | Participants receive recombinant human thymosin beta 4 injection (NL005) at a dose of 10 µg/kg administered as a slow intravenous bolus over approximately 3 minutes. The first dose is given within 4 hours after guidewire passage during primary PCI, followed by once-daily dosing on Days 2 through 7, for a total of 7 doses. Each dose is formulated in a total volume of 5 mL. |
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| NL005 20 µg/kg Group | Experimental | Participants receive recombinant human thymosin beta 4 injection (NL005) at a dose of 20 µg/kg administered as a slow intravenous bolus over approximately 3 minutes. The first dose is given within 4 hours after guidewire passage during primary PCI, followed by once-daily dosing on Days 2 through 7, for a total of 7 doses. Each dose is formulated in a total volume of 5 mL. |
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| Placebo Group | Placebo Comparator | Participants receive matching placebo (a sterile solution with identical appearance to NL005 but containing no active ingredient) administered as a slow intravenous bolus over approximately 3 minutes. The first dose is given within 4 hours after guidewire passage during primary PCI, followed by once-daily dosing on Days 2 through 7, for a total of 7 doses. Each dose is formulated in a total volume of 5 mL. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Recombinant Human Thymosin Beta 4 Injection (NL005) | Drug | NL005 is a sterile solution of recombinant human thymosin beta 4 formulated for intravenous injection. It is supplied as a 1.5 mg (1 mL) vial and stored at 2-8°C. For each dose, the appropriate volume is drawn to achieve 10 µg/kg or 20 µg/kg, and the total volume is adjusted to 5 mL with compatible diluent before administration. |
| Measure | Description | Time Frame |
|---|---|---|
| Myocardial Infarct Size (absolute) at Day 90 | Myocardial infarct size measured by late gadolinium enhancement cardiac magnetic resonance (LGE-CMR), expressed in absolute (grams). | Day 90 (±7 days) |
| Myocardial Infarct Size (relative) at Day 90 | Myocardial infarct size measured by LGE-CMR, expressed in relative (percentage of LV mass), calculated as (infarct mass / total LV mass) × 100%. | Day 90 (±7 days) |
| Measure | Description | Time Frame |
|---|---|---|
| Myocardial Infarct Size (absolute) at Day 6 | Myocardial infarct size measured by LGE-CMR, expressed in absolute (grams). | Day 6 (±1 day) |
| Myocardial Infarct Size (relative) at Day 6 | Myocardial infarct size measured by LGE-CMR, expressed in relative (percentage of LV mass), calculated as (infarct mass / total LV mass) × 100%. |
| Measure | Description | Time Frame |
|---|---|---|
| Left Ventricular Ejection Fraction (LVEF) at 1 Year | LVEF measured by cardiac ultrasound at the Day 360 visit, expressed as a percentage. | Day 360 (±14 days) |
| Quality of Life Assessed by the Minnesota Living with Heart Failure Questionnaire (MLHFQ) at 1 Year |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Yue Liu | Contact | +86-10-82890893 | liuyue@northland-bio.com | |
| Yinjian Sun | Contact | +86-10-82890893 | sunyinjian@northland-bio.com |
| Name | Affiliation | Role |
|---|---|---|
| Kefei Dou | Fuwai Hospital Chinese Academy of Medical Sciences (CAMS) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fuwai Hospital Chinese Academy of Medical Sciences (CAMS) | Beijing | Beijing Municipality | 100037 | China |
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| Placebo | Drug | The placebo is a sterile solution identical in appearance to NL005 and contains no active ingredient. It is supplied as a 1 mL vial and stored at 2-8°C. Each dose is formulated in a total volume of 5 mL and administered intravenously. |
|
| Day 6 (±1 day) |
| Microvascular Obstruction (MVO)(absolute) | MVO measured by LGE-CMR, expressed in absolute (grams). | Day 6 (±1 day), Day 90 (±7 days) |
| MVO (relative) | MVO measured by LGE-CMR, expressed in relative (percentage of LV mass), calculated as (MVO mass / total LV mass) × 100%. | Day 6 (±1 day), Day 90 (±7 days) |
| Left Ventricular Ejection Fraction (LVEF) | LVEF measured by CMR. | Day 6 (±1 day), Day 90 (±7 days) |
| Left Ventricular End Systolic Volume index (LVESVi) | LVESVi=left ventricular end systolic volume (LVESV)/body surface area (BSA, m²), LVESV measured by CMR. | Day 6 (±1 day), Day 90 (±7 days) |
| Left Ventricular End Diastolic Volume index (LVEDVi) | LVEDVi=left ventricular end diastolic volume (LVDSV)/body surface area (BSA, m²), LVEDV measured by LGE-CMR. | Day 6 (±1 day), Day 90 (±7 days) |
| LVEF at Day 90 Change from Day 6 | Change from Day 6 to Day 90. | Day 6 (±1 day), Day 90 (±7 days) |
| LVEDVi at Day 90 Change from Day 6 | Change from Day 6 to Day 90. | Day 6 (±1 day), Day 90 (±7 days) |
| LVESVi at Day 90 Change from Day 6 | Change from Day 6 to Day 90. | Day 6 (±1 day), Day 90 (±7 days) |
| Biomarkers: N-terminal pro-B-type natriuretic peptide (NT-proBNP) | Baseline (pre-dose), Day 2/3/7/30/90 |
| Biomarkers: soluble ST2 (sST2) | Baseline (pre-dose), Day 2/3/7/30/90 |
| Biomarkers: high-sensitivity cardiac troponin I (hs-cTnI) | Baseline (pre-dose), Day 2/3/7/30/90 |
| Biomarkers: creatine kinase-MB (CK-MB) | Baseline (pre-dose), Day 2/3/7/30/90 |
| Biomarkers: high-sensitivity C-reactive protein (hs-CRP) | Baseline (pre-dose), Day 2/3/7/30/90 |
| Proportion of participants with persistent MVO at Day 90. | Day 90 (±7 days) |
| Number of Participants with Treatment-Emergent Adverse Events (TEAEs) | An adverse event (AE) is any untoward medical occurrence, regardless of causal relationship to study drug. A treatment-emergent adverse event (TEAE) is defined as an event that starts or worsens in severity on or after the first dose. | First dose through Day 360 |
| Incidence of Anti-Drug Antibodies (ADA) | Baseline and Day 30 |
| Peak Concentration (Cmax) | Each participant contributes a total of 4 venous blood samples during Days 1-7, with one sample drawn at each of the following post-dose time points: 3-5 minutes, 15±3 minutes, 3±15 hours, and 6±15 hours. Plasma concentrations of NL005 are measured using a validated assay. The parameter is estimated by population PK modeling, combining data from this study with data from a prior Phase I study. | Days 1-7 (post-dose) |
| Time to Maximum Concentration (Tmax) | Each participant contributes a total of 4 venous blood samples during Days 1-7, with one sample drawn at each of the following post-dose time points: 3-5 minutes, 15±3 minutes, 3±15 hours, and 6±15 hours. Plasma concentrations of NL005 are measured using a validated assay. The parameter is estimated by population PK modeling, combining data from this study with data from a prior Phase I study. | Days 1-7 (post-dose) |
| Area under the plasma concentration-time curve from time zero to the last quantifiable rime point after administration (AUC0-t) | Each participant contributes a total of 4 venous blood samples during Days 1-7, with one sample drawn at each of the following post-dose time points: 3-5 minutes, 15±3 minutes, 3±15 hours, and 6±15 hours. Plasma concentrations of NL005 are measured using a validated assay. The parameter is estimated by population PK modeling, combining data from this study with data from a prior Phase I study. | Days 1-7 (post-dose) |
| Area under the plasma concentration-time curve from time zero to infinity (AUC0-inf) | Each participant contributes a total of 4 venous blood samples during Days 1-7, with one sample drawn at each of the following post-dose time points: 3-5 minutes, 15±3 minutes, 3±15 hours, and 6±15 hours. Plasma concentrations of NL005 are measured using a validated assay. The parameter is estimated by population PK modeling, combining data from this study with data from a prior Phase I study. | Days 1-7 (post-dose) |
| Elimination half-life (t1/2) | Each participant contributes a total of 4 venous blood samples during Days 1-7, with one sample drawn at each of the following post-dose time points: 3-5 minutes, 15±3 minutes, 3±15 hours, and 6±15 hours. Plasma concentrations of NL005 are measured using a validated assay. The parameter is estimated by population PK modeling, combining data from this study with data from a prior Phase I study. | Days 1-7 (post-dose) |
| Elimination rate constant (λz) | Each participant contributes a total of 4 venous blood samples during Days 1-7, with one sample drawn at each of the following post-dose time points: 3-5 minutes, 15±3 minutes, 3±15 hours, and 6±15 hours. Plasma concentrations of NL005 are measured using a validated assay. The parameter is estimated by population PK modeling, combining data from this study with data from a prior Phase I study. | Days 1-7 (post-dose) |
| Clearance (CL) | Each participant contributes a total of 4 venous blood samples during Days 1-7, with one sample drawn at each of the following post-dose time points: 3-5 minutes, 15±3 minutes, 3±15 hours, and 6±15 hours. Plasma concentrations of NL005 are measured using a validated assay. The parameter is estimated by population PK modeling, combining data from this study with data from a prior Phase I study. | Days 1-7 (post-dose) |
| Volume of distribution (Vz) | Each participant contributes a total of 4 venous blood samples during Days 1-7, with one sample drawn at each of the following post-dose time points: 3-5 minutes, 15±3 minutes, 3±15 hours, and 6±15 hours. Plasma concentrations of NL005 are measured using a validated assay. The parameter is estimated by population PK modeling, combining data from this study with data from a prior Phase I study. | Days 1-7 (post-dose) |
MLHFQ score at Day 360. The MLHFQ contains 21 items, each scored 0 (no impact) to 5 (very severe impact). The total score ranges from 0 to 105, where higher scores represent worse health-related quality of life.
| Day 360 (±14 days) |
| Incidence of Major Adverse Cardiovascular Event (MACE) | MACE is a composite endpoint defined as the first occurrence of any of the following: acute myocardial infarction, hospitalization for heart failure, or cardiovascular death. | First dose through Day 360 |
| Incidence of New-Onset Major Diseases at 1 Year | New-Onset Major Diseases including clinical events such as heart failure, recurrent myocardial infarction, malignancy, or death from any cause. | First dose through Day 360 |
| ID | Term |
|---|---|
| D056988 | Anterior Wall Myocardial Infarction |
| D000072657 | ST Elevation Myocardial Infarction |
| ID | Term |
|---|---|
| D009203 | Myocardial Infarction |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D014652 | Vascular Diseases |
| D007238 | Infarction |
| D007511 | Ischemia |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009336 | Necrosis |
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