Effect of RVX000222 on Time to Major Adverse Cardiovascular Events in High-Risk T2DM Subjects With CAD (BETonMACE)
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT02586155 |
|
Recruitment Status :
Completed
First Posted : October 26, 2015
Results First Posted : August 20, 2021
Last Update Posted : August 20, 2021
|
- Study Details
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Diabetes Mellitus, Type 2 Coronary Artery Disease | Drug: Apabetalone Drug: Placebo Drug: Atorvastatin Drug: Rosuvastatin | Phase 3 |
The majority (75%) of deaths in subjects with diabetes mellitus (DM) are due to atherosclerotic cardiovascular disease (CVD). Recent studies suggest a major adverse cardiovascular event (MACE) rate of >11% over 18 months in type 2 diabetes mellitus (T2DM) despite a baseline LDL-C of <2.1 mmol/L. Bromodomains (BRDs) are a family of evolutionary conserved protein-interaction modules that play key functions in chromatin organization and regulation of gene transcription. One recognized family of bromodomain-containing proteins is the bromodomain and extra-terminal (BET) family. BET inhibition represents a novel, epigenetic approach to treat CAD.
RVX000222 affects biological processes important in atherosclerosis and acute coronary events via selective inhibition of BET proteins. RVX000222 is available as a capsule formulation with standard excipients and established stability.
The BETonMACE study will focus on prevention of subsequent MACE in subjects with CAD and DM with high intensity statin therapy as co-medication.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 2425 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Triple (Participant, Care Provider, Investigator) |
| Primary Purpose: | Prevention |
| Official Title: | A Phase III Multi-Center, Double-Blind, Randomized, Parallel Group, Placebo-Controlled Clinical Trial in High-Risk Type 2 Diabetes Mellitus (T2DM) Subjects With Coronary Artery Disease (CAD) to Determine Whether Bromodomain Extraterminal Domain (BET) Inhibition Treatment With RVX000222 Increases the Time to Major Adverse Cardiovascular Events (MACE) |
| Actual Study Start Date : | November 2015 |
| Actual Primary Completion Date : | November 30, 2020 |
| Actual Study Completion Date : | June 21, 2021 |
| Arm | Intervention/treatment |
|---|---|
|
Experimental: High-Intensity statin therapy+RVX000222
Daily dose 100 mg capsule b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin)
|
Drug: Apabetalone
100 mg capsule
Other Name: RVX000222 Drug: Atorvastatin High-Intensity Statin
Other Name: Lipitor Drug: Rosuvastatin High-Intensity Statin
Other Name: Crestor |
|
Active Comparator: High-Intensity statin therapy+Placebo
Placebo (for RVX000222 100 mg capsule) b.i.d. with high-intensity statin therapy (atorvastatin or rosuvastatin)
|
Drug: Placebo
Capsule manufactured to mimic RVX000222 100 mg capsule
Other Name: Placebo (for RVX000222) Drug: Atorvastatin High-Intensity Statin
Other Name: Lipitor Drug: Rosuvastatin High-Intensity Statin
Other Name: Crestor |
- Incidence of First Occurrence of Adjudication-confirmed Narrowly Defined MACE [ Time Frame: 120 weeks ]Incidence of first occurrence of MACE narrowly defined as a single composite endpoint of Cardiovascular (CV) Death (including undetermined cause of death) or Non-fatal Myocardial Infarction (MI) or Stroke. If a subject has multiple events, only the first event contributing to the composite endpoint is counted.
- Incidence of First Occurrence of Adjudication-confirmed Broadly Defined MACE [ Time Frame: 120 weeks ]First occurrence of MACE broadly defined as a single composite endpoint of Cardiovascular Death (CVD) (including undetermined cause of death) or Non-fatal Myocardial Infarction (MI), Stroke, or Hospitalization for CVD events (including unstable angina and evidence of new or presumed new progressive obstructive coronary disease or emergency revascularization procedures at any time and urgent revascularization procedures ≥30 days after the index event as defined by Hicks et al., 2014) . If a subject has multiple events, only the first event contributing to the composite endpoint is counted.
- Incidence of Hospitalization for Congestive Heart Failure (CHF) [ Time Frame: 120 weeks ]
- Incidence of All-cause Mortality [ Time Frame: 120 weeks ]
- Change in Apolipoprotein A1 (ApoA-I) Concentration From Baseline Over Time Within and Between Treatment Groups [ Time Frame: 120 weeks ]
- Change in Apolipoprotein B (apoB) Concentration From Baseline Over Time Within and Between Treatment Groups [ Time Frame: 120 weeks ]
- Change in LDL-C Concentration From Baseline Over Time Within and Between Treatment Groups [ Time Frame: 120 weeks ]
- Change in HDL-C Concentration From Baseline Over Time Within and Between Treatment Groups [ Time Frame: 120 weeks ]
- Change in Triglyceride (TG) Concentration From Baseline Over Time Within and Between Treatment Groups [ Time Frame: 120 weeks ]
- Change in Hemoglobin (Hb) A1c From Baseline Over Time Within and Between Treatment Groups [ Time Frame: 120 weeks ]
- Change in Glucose From Baseline Over Time Between and Within Treatment Groups [ Time Frame: 120 weeks ]
- Change in Alkaline Phosphatase (ALP) From Baseline Over Time Within and Between Treatment Groups [ Time Frame: 172 weeks ]
- Change in C Reactive Protein (CRP) Concentration From Baseline Over Time Within and Between Treatment Groups [ Time Frame: 52 weeks ]
- Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline Over Time Within and Between Treatment Groups for Subjects With Impaired Renal Function at Baseline (eGFR <60 mL/Min/1.7m2) [ Time Frame: 120 weeks ]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
• ACS event of either unstable angina or myocardial infarction 7-90 days prior Visit 1:
Unstable angina: for a qualifying unstable angina event, each of components (a), (b), and (c) must be satisfied: a.) Characteristic ischemic pain or discomfort in chest/associated referral areas, occurring at rest/with minimal exertion b.) ECG changes consistent with acute myocardial ischemia based on new/presumed ST elevation/depression or T-wave inversion c.) Objective evidence of obstructive CAD based on 1+ of the following: i. New/presumed new evidence of myocardial ischemia/infarction by perfusion imaging ii. New/presumed new regional wall motion abnormality iii. Current evidence of at least 1 epicardial coronary artery stenosis ≥70% by coronary angiography iv. Need for coronary revascularization for the index ACS event, including a percutaneous coronary intervention (PCI) with or without coronary stenting.
Prior MI 7-90 days prior screening treated with or without a percutaneous coronary intervention (PCI). For a qualifying event of MI 2 of the following 3 criteria must be satisfied: a.) Characteristic ischemic chest pain/pain in associated referral areas b.) Dynamic elevation of troponin T/I or CKMB if troponinT/I is unavailable at local lab (at least >ULN for lab) c.) Development of new Q-waves in ≥2 adjacent ECG leads or development of new dominant R wave in V1
- Documented diagnosis of T2DM (1+ of the following criteria): Documented history of T2DM, History of taking diabetes medication, and/or HbA1c ≥6.5% at Visit 1
- For males HDL-C<40 mg/dL(1.04 mmol/L), for females HDL-C<45 mg/dL(1.17 mmol/L) at Visit 1
- Subjects currently not on high intensity statin therapy could start rosuvastatin at Visit 1 and those currently on therapy besides atorvastatin/rosuvastatin can be switched to rosuvastatin at Visit 1
- Female subjects of non-childbearing potential (post-surgical sterilization/post-menopausal) or if childbearing potential have neg urine pregnancy test and be willing and able to use non-hormonal birth control (non-hormonal IUD, condom or diaphragm) or remain abstinent from Screening to Follow-up Visit
- Give signed informed consent
Exclusion Criteria:
- Heart disease which will w/in 90 days of Visit 1 likely need coronary bypass, PCI, cardiac transplantation, surgical repair and/or replacement
- Previous/current diagnosis of severe heart failure or documented LVEF<25% determined by contrast left ventriculography, radionuclide ventriculography or echocardiography. Absence of LVEF measurement in subject w/out a previous/current diagnosis of heart failure does not exclude entry into study
- Evidence of cardiac EP instability incl. history of uncontrolled ventricular arrhythmias, atrial fibrillation/flutter or supraventricular tachycardias w/ a ventricular response HR>100bpm at rest w/in 4 wks prior Visit 1
- CABG w/in 90 days prior Visit 1
- Evidence of severe renal impairment as determined by either eGFR<30 mL/min/1.7m2 at Visit 1 or current need for dialysis
- Uncontrolled hypertension defined as 2 consecutive measurements of sitting BP of systolic>180 mmHg or diastolic>100 mmHg at Visit 1
- Treatment w/ immunosuppressants w/in 12 mos prior Visit 1
- Use of fibrates at any dose or niacin/nicotinic acid 250+ mg w/in 30 days prior Visit 1
- Known allergy/sensitivity to any ingredient in IMP
- History of intolerance to atorvastatin/rosuvastatin
- Triglycerides>400 mg/dL (4.52 mmol/L) at Visit 1
- Any medical/surgical condition which might significantly alter absorption, distribution, metabolism or excretion of medication
- Evidence of cirrhosis from liver imaging/biopsy, history of hepatic encephalopathy, esophageal/gastric varices, active hepatitis or prior porta-caval shunt procedure or a Child-Pugh score of ≥5 points
- ALT/AST>1.5xULN by central lab at Visit 1
- Tot. bilirubin>ULN by central lab at Visit 1
- History of malignancy of any organ syst treated/untreated w/in the past 2 yrs whether or not there is evidence of local recurrence/metastases except localized basal skin cell carcinoma
- History/evidence of drug/alcohol abuse w/in 12 mos of Visit 1
- Pregnancy
- Any condition which may place subject at higher risk from his/her participation in the study or is likely to prevent subject from completing/complying w/ requirements of study
- Use of other investigational drugs and devices w/in 30 days or 5 half-lives of Visit 1, whichever is longer
- History of noncompliance to medical regimens or unwillingness to comply w/ study protocol
- Any condition that would confound the evaluation/interpretation of efficacy and/or safety data
- Persons directly involved in execution of this protocol
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02586155
Show 214 study locations
| Study Chair: | Kausik Ray, MD | Imperial College London |
Documents provided by Resverlogix Corp:
Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Resverlogix Corp |
| ClinicalTrials.gov Identifier: | NCT02586155 |
| Other Study ID Numbers: |
RVX222-CS-015 |
| First Posted: | October 26, 2015 Key Record Dates |
| Results First Posted: | August 20, 2021 |
| Last Update Posted: | August 20, 2021 |
| Last Verified: | July 2021 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
|
Coronary Artery Disease Myocardial Ischemia Coronary Disease Diabetes Mellitus Diabetes Mellitus, Type 2 Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases Heart Diseases Cardiovascular Diseases Arteriosclerosis |
Arterial Occlusive Diseases Vascular Diseases Atorvastatin Rosuvastatin Calcium Anticholesteremic Agents Hypolipidemic Agents Antimetabolites Molecular Mechanisms of Pharmacological Action Lipid Regulating Agents Hydroxymethylglutaryl-CoA Reductase Inhibitors Enzyme Inhibitors |