ApoA-I Synthesis Stimulation and Intravascular Ultrasound for Coronary Atheroma Regression Evaluation

NCT01067820 | Completed Phase 2 DMC

• 1 other identifier: RVX222-CS-007
• Study Type: interventional
• Target: 324
• Locations: 8 countries
• Sites: 58

Brief Summary

This study is designed to characterize the early effects of ApoA-I synthesis with RVX000222 on coronary atherosclerotic disease when administered to patients with coronary artery disease and have a low HDL-C level, as assessed by Intravascular Ultrasound (IVUS) in addition to standard background therapy.

Conditions

Coronary Artery Disease

Keywords

ApolipoproteinA1; HDL-C; Atherosclerosis

Outcome Measures

Primary Outcomes (1)

• The nominal change in percent atheroma volume (PAV) from baseline to 26 weeks postrandomization, as determined by intravascular ultrasound (IVUS) within the RVX000222 treated group.

  To evaluate the effect of RVX000222 on the change in burden of coronary atherosclerosis, as measured by percent atheroma volume (PAV), in patients with coronary artery disease and a low level of HDL-C requiring angiography for a clinical indication.

  baseline to 26 weeks postrandomization

Secondary Outcomes (6)

• Nominal change in percent atheroma volume (PAV), from baseline to 26 weeks postrandomization, as determined by intravascular ultrasound (IVUS) within the RVX000222 treated group compared to placebo.

  baseline to 26 weeks postrandomization

• Nominal change in total atheroma volume (TAV) from baseline to 26 weeks postrandomization, as determined by intravascular ultrasound (IVUS) in the RVX000222 treated group as well as compared to placebo.

  baseline to 26 weeks postrandomization

• Nominal change in total atheroma volume (TAV) for the 10-mm sub-segment with the greatest disease burden at baseline, within the RVX000222 treated group as well as compared to placebo.

  baseline to 26 weeks postrandomization

• Proportion of patients with regression of coronary atherosclerosis, defined as a change in percent atheroma volume (PAV) from baseline to 26 weeks of less than zero (i.e. any reduction in PAV).

  baseline to 26 weeks postrandomization

• Percent change from baseline in HDL-C, ApoA-I, and HDL-subclasses at various time points within the RVX000222 treated group as well as compared to placebo.

  Week 14 and 26

Study Arms (2)

RVX000222, 200 mg daily

EXPERIMENTAL

Drug: RVX000222

Placebo

PLACEBO COMPARATOR

Drug: Placebo RVX000222

Interventions

RVX000222 DRUG

capsule, 200 mg, administer with food, 100 mg twice daily 10-12 hrs apart, 26 weeks

RVX000222, 200 mg daily

Placebo RVX000222 DRUG

capsule, administer with food, twice daily 10-12 hrs apart, 26 weeks

Placebo

Eligibility Criteria

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

You may qualify if:

• Male and female patient's \>/= 18 years of age who are scheduled to undergo coronary angiography for a clinical indication.
• Women of child-bearing potential, that is, women not surgically sterilized and between menarche and 1 year post menopause, must test negative for pregnancy at the time of enrollment based on a serum pregnancy test and agree to use a reliable method of birth control (for example, use of oral contraceptives or Norplant; a reliable barrier method of birth control (diaphragms with contraceptive jelly; cervical caps with contraceptive jelly; condoms with contraceptive foam; intrauterine devices; partner with vasectomy; or abstinence) during the study and for one month following the last dose of study drug.
• Current (Local lab within 60 days prior to Visit 1). HDLC of \</= 45 mg/dL (1.2 mmol/L) for females and HDLC of \</=40 mg/dL (1.0 mmol/L) for males.
• In the opinion of the investigator patients currently not on statin therapy will be able to start either atorvastatin (10 mg, 20mg or 40mg) or rosuvastatin (5mg, 10mg or 20 mg) at Visit 1.
• In the opinion of the investigator patients currently on statin therapy other than atorvastatin (10 mg, 20mg or 40mg) or rosuvastatin (5mg, 10mg or 20 mg) can be switched to rosuvastatin (5mg, 10mg or 20 mg) at Visit 1.
• Patients must meet all of the following criteria at the qualifying coronary catheterization procedure:
• A. Entire Coronary Circulation: Angiographic evidence of coronary heart disease as defined by at least one lesion in any of the three major native coronary arteries that has \>20 percent reduction in lumen diameter by angiographic visual estimation or prior history of PCI. This vessel need not be the target coronary artery for IVUS. Any vessel with previous PCI may not be used as the target coronary artery.
• B. Left Main Coronary Artery: Must not have a \>50 percent reduction in lumen diameter by visual angiographic estimation.
• C. Target Coronary Artery for IVUS: Must be accessible to the IVUS catheter. Must have a \<50 percent reduction in lumen diameter by angiographic visual estimation throughout a segment of at least 40 mm in length (the "target segment"). A lesion of up to 60 percent stenosis is permitted, distal to the target segment. A single branch of the "target vessel" may have a narrowing up to but \<70 percent by visual estimation, as long as the target segment contains no lesion \>50 percent, provided that the branch in question is not a target for PCI or CABG. Has not undergone prior percutaneous coronary intervention or coronary artery bypass graft surgery. The target vessel is not currently a candidate for intervention or a likely candidate for intervention over the next 6 months. The target vessel may not be a bypass graft. The target vessel may not be a bypassed vessel. The target vessel may not be the culprit vessel for a previous MI.
• Have given signed informed consent to participate in this study.

You may not qualify if:

• Clinically significant heart disease which will require coronary bypass, PCI, cardiac transplantation, surgical repair and/or replacement during the course of the study.
• Any elective surgical procedure that would require general anesthesia during the course of the study.
• Coronary artery bypass graft (CABG) procedure within the past 90 days.
• Previous or current diagnosis of severe heart failure (NYHA Class III-IV) or a documented left ventricular ejection fraction (LVEF) of \<25 percent as determined by contrast left ventriculography, radionuclide ventriculography or echocardiography, the absence of an LVEF measurement in a patient without a previous or current diagnosis of heart failure does not prohibit entry into the study.
• Patients with evidence of cardiac electrophysiologic instability including a history of uncontrolled ventricular arrhythmias, uncontrolled atrial fibrillation/flutter or uncontrolled supraventricular tachycardias with a ventricular response heart rate of \>100 beats per minute at rest within 4 weeks prior to Visit 1.
• Evidence of renal impairment as determined by any one of the following:
• serum creatinine \>1.5 mg/dL (\>133 micromol/L) by central lab at Visit 1,
• a calculated creatinine clearance less than 60 ml/min at Visit 1
• a history of dialysis,
• a history of nephrotic syndrome.
• Have hypertension that is uncontrolled defined as 2 consecutive measurements of sitting blood pressure of systolic \>160 mm Hg or diastolic \>95 mm Hg at Visit 1.
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive beta-hCG laboratory test (\>/= 5 mIU/mL).
• Current or recent (within 12 month prior to Visit 1) treatment with immunosuppressants (eg, Cyclosporine).
• Use of fibrates any dose or niacin/nicotinic acid 250 mg or more within 90 days prior to Visit 1.
• Atorvastatin \>40 mg daily at Visit 1.

Sponsors & Collaborators

• Resverlogix Corp: lead
• The Cleveland Clinic: collaborator

Study Sites (58)

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La Plata, Buenos Aires, 1900, Argentina

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Buenos Aires, C1180AAX, Argentina

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Buenos Aires, C1428DCO, Argentina

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Corrientes, 3400, Argentina

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Córdoba, 5000, Argentina

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Córdoba, X5000EPU, Argentina

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Córdoba, X5003DCE, Argentina

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Córdoba, X5006IKK, Argentina

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Córdoba, X5016KEH, Argentina

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San Isidro, B1642DJN, Argentina

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Brussels, 1200, Belgium

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Charleroi, 6000, Belgium

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Edegem, B-2650, Belgium

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Genk, 3600, Belgium

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Brasília, 70390-700, Brazil

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Cariacica, 29156-580, Brazil

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Curitiba, 80320-320, Brazil

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Goiânia, 74223-130, Brazil

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Porto Alegre, 90020-090, Brazil

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São Paulo, 04012-909, Brazil

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São Paulo, 05403-000, Brazil

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Uberlândia, 38400-368, Brazil

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Budapest, H-1023, Hungary

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Budapest, H-1106, Hungary

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Budapest, H-1122, Hungary

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Budapest, H-1134, Hungary

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Pécs, H-7624, Hungary

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Szeged, H-6720, Hungary

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Alkmaar, 1814, Netherlands

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Amsterdam, 1091, Netherlands

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Eindhoven, 5623, Netherlands

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Enschede, 7513, Netherlands

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Nijmegen, 6532, Netherlands

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Rotterdam, 3079, Netherlands

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Zwolle, 8011, Netherlands

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Katowice, 40-635, Poland

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Warsaw, 02-507, Poland

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Warsaw, 04-628, Poland

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Moscow, 101990, Russia

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Moscow, 117931, Russia

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Moscow, 121552, Russia

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Moscow, 143420, Russia

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Orenburg, 460000, Russia

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Saint Petersburg, 191104, Russia

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Saint Petersburg, 197341, Russia

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Tomsk, 634012, Russia

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Badalona, 08916, Spain

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Barcelona, 08035, Spain

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Barcelona, 08907, Spain

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Cartagena, 30203, Spain

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Galdakao, 48960, Spain

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Gijón, 33203, Spain

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Madrid, 28040, Spain

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Madrid, 28046, Spain

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Málaga, 29010, Spain

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Santander, 39008, Spain

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Santiago de Compostela, 15706, Spain

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Vigo, 36214, Spain

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Related Publications (1)

• Nicholls SJ, Puri R, Wolski K, Ballantyne CM, Barter PJ, Brewer HB, Kastelein JJ, Hu B, Uno K, Kataoka Y, Herrman JP, Merkely B, Borgman M, Nissen SE. Effect of the BET Protein Inhibitor, RVX-208, on Progression of Coronary Atherosclerosis: Results of the Phase 2b, Randomized, Double-Blind, Multicenter, ASSURE Trial. Am J Cardiovasc Drugs. 2016 Feb;16(1):55-65. doi: 10.1007/s40256-015-0146-z.

  PMID: 26385396 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease; Atherosclerosis

Interventions

apabetalone

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Study Officials

• Stephen Nicholls, MBBS, PhD

  Intravascular Ultrasound Core Lab, Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2010
• First Posted: February 12, 2010
• Study Start: September 1, 2011
• Primary Completion: May 1, 2013
• Study Completion: June 1, 2013
• Last Updated: June 4, 2013

Record last verified: 2013-06

Locations

NL (7); AR (10); BR (8); BE (4); HU (6); RU (8); ES (12); PL (3)