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Coronary Artery DiseasePhase 2ASSURE INCT01067820

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

A Phase 2 study testing RVX000222 in people with Coronary Artery Disease, run by Resverlogix Corp at 58 sites in 8 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Coronary Artery Disease
What is being tested?
RVX000222
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
324 participants
Where
58 sitesin 8 countries
Study dates
Sep 2011to Jun 2013
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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.
  • Left Main Coronary Artery: Must not have a >50 percent reduction in lumen diameter by visual angiographic estimation.
  • 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.

Who cannot join

  • 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:
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  • 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.
  • Rosuvastatin >20 mg daily at Visit 1.
  • Triglycerides >400 mg/dL at Visit 1.
  • Any medical or surgical condition which might significantly alter the absorption, distribution, metabolism or excretion of medication including, but not limited to any of the following: cholecystitis, Crohn's disease, ulcerative colitis, or any gastric bypass alteration.
  • Evidence of hepatic disease as determined by any one of the following: a history of hepatic encephalopathy, history of Hepatitis B, C or E, history of esophageal varices, history of porta-caval shunt. Any one of the following liver enzymes that is >ULN by central lab at Visit 1: ALT, AST, GGT
  • A total bilirubin that is >ULN by central lab at Visit 1.
  • History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin.
  • History or evidence of drug or alcohol abuse within the last 12 months.
  • Any surgical or medical condition, which in the opinion of the investigator, may place the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study.
  • Use of other investigational drugs and devices at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer.
  • History of noncompliance to medical regimens or unwillingness to comply with the study protocol.
  • Any condition that in the opinion of the investigator would confound the evaluation and interpretation of efficacy and/or safety data.
  • Persons directly involved in the execution of this protocol.

Trial locations and contacts

58 sites in 8 countries.

58 sites in 8 countries

Spain12 sites

  • Study site

    Badalona, 08916

  • Study site

    Barcelona, 08035

  • Study site

    Barcelona, 08907

  • Study site

    Cartagena, 30203

  • Study site

    Galdakao, 48960

  • Study site

    Gijón, 33203

  • Study site

    Madrid, 28040

  • Study site

    Madrid, 28046

  • Study site

    Málaga, 29010

  • Study site

    Santander, 39008

  • Study site

    Santiago de Compostela, 15706

  • Study site

    Vigo, 36214

Other trials in Spain

Argentina10 sites

  • Study site

    Buenos Aires, C1180AAX

  • Study site

    Buenos Aires, C1428DCO

  • Study site

    Córdoba, 5000

  • Study site

    Córdoba, X5000EPU

  • Study site

    Córdoba, X5003DCE

  • Study site

    Córdoba, X5006IKK

  • Study site

    Córdoba, X5016KEH

  • Study site

    Corrientes, 3400

  • Study site

    La Plata, Buenos Aires, 1900

  • Study site

    San Isidro, B1642DJN

Other trials in Argentina

Brazil8 sites

  • Study site

    Brasília, 70390-700

  • Study site

    Cariacica, 29156-580

  • Study site

    Curitiba, 80320-320

  • Study site

    Goiânia, 74223-130

  • Study site

    Porto Alegre, 90020-090

  • Study site

    São Paulo, 04012-909

  • Study site

    São Paulo, 05403-000

  • Study site

    Uberlândia, 38400-368

Other trials in Brazil

Russia8 sites

  • Study site

    Moscow, 101990

  • Study site

    Moscow, 117931

  • Study site

    Moscow, 121552

  • Study site

    Moscow, 143420

  • Study site

    Orenburg, 460000

  • Study site

    Saint Petersburg, 191104

  • Study site

    Saint Petersburg, 197341

  • Study site

    Tomsk, 634012

Other trials in Russia

Netherlands7 sites

  • Study site

    Alkmaar, 1814

  • Study site

    Amsterdam, 1091

  • Study site

    Eindhoven, 5623

  • Study site

    Enschede, 7513

  • Study site

    Nijmegen, 6532

  • Study site

    Rotterdam, 3079

  • Study site

    Zwolle, 8011

Other trials in Netherlands

Hungary6 sites

  • Study site

    Budapest, H-1023

  • Study site

    Budapest, H-1106

  • Study site

    Budapest, H-1122

  • Study site

    Budapest, H-1134

  • Study site

    Pécs, H-7624

  • Study site

    Szeged, H-6720

Other trials in Hungary

Belgium4 sites

  • Study site

    Brussels, 1200

  • Study site

    Charleroi, 6000

  • Study site

    Edegem, B-2650

  • Study site

    Genk, 3600

Other trials in Belgium

Poland3 sites

  • Study site

    Katowice, 40-635

  • Study site

    Warsaw, 02-507

  • Study site

    Warsaw, 04-628

Other trials in Poland

About this study

Official title: Phase IIb Multi-center, Double-blind, Randomized, Parallel Group, Placebo-controlled Clinical Trial for the Assessment of Coronary Plaque Changes With RVX000222 as Determined by Intravascular Ultrasound

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.

Read the detailed description

One-third of the US population, almost 80 million adults, have cardiovascular disease and mortality associated with heart disease still remains as a leading cause of death around the world. The major risk factors for cardiovascular disease associated with atherosclerosis is dyslipidemia, characterized by high levels of low density lipoprotein (LDL) and/or low levels of high density lipoprotein (HDL). The widespread use of statins in patients at risk for cardiovascular disease has led to lower LDL levels but has had little effect on HDL levels. HDL has a well established role in atherosclerosis and cardiovascular disease protection. HDL mediates the removal of cholesterol from the atherosclerotic plaques for elimination from the body. The major component of HDL consists of apolipoprotein A-I (ApoA I). Recent intervention studies with synthetic HDL particles and recombinant ApoA-I have shown that HDL has the capacity to reverse coronary atherosclerosis. Increasing ApoA-I is likely to have a favorable effect on atherosclerotic plaque stability and size and on cardiovascular diseases. RVX000222 is a member of a novel class of small molecules that are candidates for the treatment of dyslipidemia by increasing plasma levels of HDL through increased ApoA-I transcription.

Being tested
RVX000222, Placebo RVX000222
Keywords
ApolipoproteinA1, HDL-C, Atherosclerosis
Medical subject headings
Coronary Artery Disease, Atherosclerosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RVX000222Drug

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

  • Placebo RVX000222Drug

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

Study groups in NCT01067820
Study groupRoleWhat they receive
RVX000222, 200 mg dailyExperimentalNot described
Receives: Drug: RVX000222
PlaceboPlacebo comparatorNot described
Receives: Drug: Placebo RVX000222

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: baseline to 26 weeks postrandomization

Secondary outcomes (6)

  1. 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.

    To evaluate the effect of RVX000222 on the change in total atheroma volume (TAV), changes in the 10-mm most diseased artery sub-segment containing the most amount of disease and the percentage of patients who demonstrate regression of coronary atherosclerosis.

    Measured: baseline to 26 weeks postrandomization

  2. 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.

    To evaluate the effect of RVX000222 on the change in total atheroma volume (TAV), changes in the 10-mm most diseased artery sub-segment containing the most amount of disease and the percentage of patients who demonstrate regression of coronary atherosclerosis.

    Measured: baseline to 26 weeks postrandomization

  3. 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.

    To evaluate the effect of RVX000222 on the change in total atheroma volume (TAV), changes in the 10-mm most diseased artery sub-segment containing the most amount of disease and the percentage of patients who demonstrate regression of coronary atherosclerosis.

    Measured: baseline to 26 weeks postrandomization

  4. 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).

    To evaluate the effect of RVX000222 on the change in total atheroma volume (TAV), changes in the 10-mm most diseased artery sub-segment containing the most amount of disease and the percentage of patients who demonstrate regression of coronary atherosclerosis.

    Measured: baseline to 26 weeks postrandomization

  5. 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.

    To evaluate the effect of RVX000222 on biomarkers (HDL-C, ApoA-I, HDL-subclasses) at various time points.

    Measured: Week 14 and 26

  6. Incidence of adverse events by treatment group, including major adverse cardiac events (MACE) (death, MI, stroke, coronary revascularization, hospitalization for ACS or heart failure).

    To evaluate the safety and tolerability of RVX000222.

    Measured: Continuous

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Feb 2010 (estimated)
  2. Study startSep 2011
  3. Primary completionMay 2013
  4. Study completionJun 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
324 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01067820
Sponsor's protocol ID
RVX222-CS-007
Acronym
ASSURE I
Status last verified
Jun 2013
First submitted
10 Feb 2010
Last updated
4 Jun 2013
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 26385396

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing RVX000222 in people with Coronary Artery Disease, run by Resverlogix Corp at 58 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Jun 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 58 sites in Spain, Argentina, Brazil, Russia, Netherlands and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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. (time frame: baseline to 26 weeks postrandomization). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01067820, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2013.

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ASSURE I Clinical Trial NCT01067820 | AzTrials