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Methods of treating and protecting against cardiac disease, cardiovascular disease and related conditions and symptoms

A cardiovascular and heart disease technology, applied in the field of mammalian subjects, can solve problems such as the contradiction between the functions of heart disease, achieve cardioprotection, anti-atherosclerotic myocardial protection, and prevent myocardial fibrosis.

Pending Publication Date: 2020-08-28
ALPHACORE PHARM LLC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the role of LCAT during RCTs is consistent with the findings of low LCAT activity and increased pre-β-HDL in cardiac patients, there are conflicting data and findings regarding the functional interrelationship between HDL, LCAT, and cardiac disease in patients

Method used

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  • Methods of treating and protecting against cardiac disease, cardiovascular disease and related conditions and symptoms
  • Methods of treating and protecting against cardiac disease, cardiovascular disease and related conditions and symptoms
  • Methods of treating and protecting against cardiac disease, cardiovascular disease and related conditions and symptoms

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0185] Example 1 - Single Dose Escalation (SAD) Study of MEDI6012 in Subjects with Stable Coronary Artery Disease (CAD)

[0186] Review of Research Design

[0187] A phase 2a randomized, double-blind (subject / investigator blinded; sponsor informed), placebo-controlled, dose-escalation study to evaluate Safety, PK / PD, and immunogenicity of single intravenous (IV / IV infusion) and subcutaneous (SC) doses of MEDI6012. A total of 48 subjects participated in the study at 10 study sites in the United States to evaluate the following 4 dose levels (cohorts) of MEDI6012 administered by IV: 24 mg, 80 mg, 240 mg, and 800 mg (cohort 1 -4); and the following 2 dose levels (cohorts) of MEDI6012 administered by SC injection: 80 mg and 600 mg, shown as figure 1 Groups 6 and 7 in . For each cohort, 8 subjects were randomized in a 6:2 ratio to receive MEDI6012 or placebo. For the IV dose cohort, MEDI6012, the investigational product, was administered as a 1 hour IV infusion in this study. ...

example 2

[0250] Example 2 - Clinical Trial Involving Treatment of Subjects with Stable Atherosclerotic Cardiovascular Disease (CVD) with Repeated Doses of MEDI6012 (rhLCAT)

[0251] overall experimental design

[0252] A Phase 2a randomized, blinded, placebo-controlled study was designed to evaluate the safety of repeated weekly doses of MEDI6012 (Multiple Ascending Dose (MAD)) in patients with stable atherosclerotic cardiovascular disease , pharmacokinetics and pharmacodynamics. This dose-escalation study was conducted to evaluate the safety, PK / PD, and immunogenicity of repeated doses of MEDI6012 in adult subjects with stable atherosclerotic CVD. Randomize at least 32 subjects at approximately 10 study sites in the United States (USA) to evaluate 4 dose levels (in cohorts 1-3) of MEDI6012 (40 mg, 120 mg, 300 mg) and include a 300 mg loading An IV bolus dosing regimen of MEDI6012 at the (first) dose followed by a 150 mg maintenance (second) dose at 48 hours and a 100 mg maintenance ...

example 3

[0307] Dose Selection Criteria for Cohort 4 of the MAD Study

[0308] PD observations from the single-dose ramp study of MEDI6012 as described in Example 1 and from the cohorts (Cohorts 1-3) analyzed in the MAD study as described in Example 2 above demonstrated that the rates of increase in HDL-C and apoAl were Dose dependent. Additional studies in subjects with cardiac and / or cardiovascular disease (e.g., ACS and acute MI) (maximizing the rate of increase in HDL-C and / or apoA1 after the first and second doses of MEDI6012, as Rationale for Combining the Antiatherogenic Effects of Enhanced Cholesterol Reverse Transport with the Cardioprotective Effects of HDL-C and / or apoAl (as found in the cohort described herein following MEDI6012 dosing and administration) expected to result in multiple benefits for CHD patients (also supported by reports: Gordts et al., 2013, Gene Ther. [Gene Therapy], 20(11):1053-61; Kalakech et al., 2014, PLoS One [Plos Museum: General], 9(9):e107950; M...

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Abstract

Provided are methods of treating subjects having, or at risk of having, heart disease, cardiovascular disease, coronary artery disease, cerebrovascular disease, acute or chronic renal disease, and / orsymptoms thereof with certain therapeutically effective doses and dosing regimens comprising an isolated and purified lecithin-cholesterol acyltransferase (LCAT) enzyme, in particular, a recombinant human LCAT (rhLCAT) enzyme, e.g., MEDI6012. The methods involving administration of the described doses of rhLCAT increase serum levels of high density lipoprotein (HDL) and apolipoprotein A1 (apoA1) and decrease, or do not appreciably increase, serum levels of apolipoprotein B in the treated subjects, thus affording treatment of heart disease, heart-related diseases and coronary artery disease. The methods involving the described dosing regimens and doses of rhLCAT or MEDI6012 administered to a subject further provide cardio-, myocardio- and cardiovascular protection for the subject, includingprotection against ischemic stroke, myocardiocyte apoptosis, atherosclerosis progression and the like.

Description

Background technique [0001] According to the World Health Organization, cardiovascular disease is a leading cause of morbidity and mortality worldwide. In 2015, approximately 17.7 million people worldwide died from cardiovascular disease, accounting for 31% of the global deaths that year. Of these deaths, an estimated 7.4 million were due to coronary heart disease (CHD), while 6.7 million were due to stroke. Heart disease remains the leading cause of death in the U.S. for men and women of most races, killing about 630,000 a year, according to the Centers for Disease Control and Prevention. Coronary heart disease is the most common heart disease in the United States; more than 360,000 people died in 2015. Heart disease and related coronary heart diseases and syndromes are projected to remain the leading cause of mortality worldwide for the next decade and beyond. [0002] Heart and coronary artery disease not only affects patients with cardiovascular disease, but also poses ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/45A61P9/00A61P9/10C12N9/10C12N15/54G01N33/50
CPCA61K38/45A61P9/10A61P9/00C12N9/1029C12Y203/01043A61K9/0019
Inventor R.T.小乔治C-Y.金
Owner ALPHACORE PHARM LLC