Clinical Trials Register

Summary
EudraCT Number:	2010-023801-36
Sponsor's Protocol Code Number:	RVX222-CS-007
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-08-10
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Netherlands - Competent Authority

A.2

EudraCT number

2010-023801-36

A.3

Full title of the trial

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Not applicable

A.3.2

Name or abbreviated title of the trial where available

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

A.4.1

Sponsor's protocol code number

RVX222-CS-007

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Resverlogix Corp.
B.1.3.4	Country	Canada
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Resverlogix Corp.
B.4.2	Country	Canada
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Resverlogix Corp.
B.5.2	Functional name of contact point	Assure Clinical Trial Inform. Desk
B.5.3	Address:
B.5.3.1	Street Address	279 Midpark Way SE, Suite 202
B.5.3.2	Town/ city	Calgary
B.5.3.3	Post code	AB T2X 1M2
B.5.3.4	Country	Canada
B.5.4	Telephone number	+1403256400
B.5.5	Fax number	+14032568495
B.5.6	E-mail	assureinfo@resverlogix.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	RVX000222
D.3.2	Product code	RVX000222
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	RVX000222
D.3.9.3	Other descriptive name	RVX000222
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule, hard
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Coronary Artery Disease

E.1.1.1

Medical condition in easily understood language

Coronary Artery Disease

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	13.1
E.1.2	Level	PT
E.1.2	Classification code	10011078
E.1.2	Term	Coronary artery disease
E.1.2	System Organ Class	10007541 - Cardiac disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

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.

E.2.2

Secondary objectives of the trial

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

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

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.

Protocol RVX222-CS-007, Amendment # 2; 22 MARCH 2011.
Inclusion and exclusion criteria are the same as for the main study. The
purpose of this genetic research is to generate data for use in future retrospective analyses. The aim is to better understand the impact of genetic variations on response to drug treatment and how it can be utilized to bring better drugs to market. To achieve this goal a systematic collection of DNA for genetic analysis (derived from blood samples taken from consenting study patients) will be implemented
across a broad range of relevant clinical studies. The ability to acquire appropriate consent to collect blood samples to establish an archive and allow future metaanalysis of data derived from a number of studies for
RVX000222 is of the utmost importance.

E.3

Principal inclusion criteria

1. Male and female patient’s ≥18 years of age who are scheduled to undergo coronary angiography for a clinical indication.
2. 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.
3. Current (Local lab within 30 days prior to Visit 1)
HDL-C of ≤45 mg/dL (1.2 mmol/L) for females
HDL-C of ≤40 mg/dL (1.0 mmol/L) for males.
4. 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.
5. 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.
6. 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% 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% 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% 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% stenosis is permitted, distal to the target segment. A single branch of the “target vessel” may have a narrowing up to but <70% by visual estimation, as long as the target segment contains no lesion >50%, 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.
7. Have given signed informed consent to participate in this study.

E.4

Principal exclusion criteria

1. Clinically significant heart disease which will require coronary bypass, PCI, cardiac transplantation, surgical repair and/or replacement during the course of the study.
2. Any elective surgical procedure that would require general anesthesia during the course of the study
3. Coronary artery bypass graft (CABG) procedure within the past 90 days.
4. Previous or current diagnosis of severe heart failure (NYHA Class III-IV) or a documented left ventricular ejection fraction (LVEF) of <25% 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.
5. 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.
6. Evidence of renal impairment as determined by any one of the following: serum creatinine >1.5 mg/dL (>133 mcmol/L) by central lab at Visit 1,
a history of dialysis, or a history of nephrotic syndrome.
7. 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.
8. 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 ß-hCG laboratory test (≥5 mIU/mL).
9. Current or recent (within 12 month prior to Visit 1) treatment with immunosuppressants (eg, Cyclosporine).
10. Use of fibrates any dose or niacin/nicotinic acid 250 mg or more within 90 days prior to Visit 1.
11. Atorvastatin 80 mg daily at Visit 1
12. Rosuvastatin 40 mg daily at Visit 1
13. Triglycerides >400 mg/dL at Visit 1.
14. 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.
15. Evidence of hepatic disease as determined by any one of the following:
- ALT, AST, GGT that is >ULN by central lab at Visit 1
- a history of hepatic encephalopathy
- history of Hepatitis B, C or E
- history of esophageal varices
- history of porta-caval shunt.
16. A total bilirubin that is >ULN by central lab at Visit 1
17. 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.
18. History or evidence of drug or alcohol abuse within the last 12 months.
19. 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.
20. 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.
21. History of noncompliance to medical regimens or unwillingness to comply with the study protocol.
22. Any condition that in the opinion of the investigator would confound the evaluation and interpretation of efficacy and/or safety data.
23. Persons directly involved in the execution of this protocol.

E.5 End points

E.5.1

Primary end point(s)

The nominal change in percent atheroma volume (PAV), from baseline to 26 weeks post-randomization, as determined by intravascular ultrasound (IVUS), within the RVX000222 treated groups.

E.5.1.1

Timepoint(s) of evaluation of this end point

26 weeks post-randomization

E.5.2

Secondary end point(s)

• Nominal change in percent atheroma volume (PAV), from baseline to 26 weeks post-randomization, as determined by intravascular ultrasound (IVUS) within the RVX000222 treated group compared to placebo
• Nominal change in total atheroma volume (TAV) from baseline to 26 weeks post-randomization, as determined by intravascular ultrasound (IVUS) within the RVX000222 treated group as well as compared to placebo.
• 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.
• 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).
• 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.
• Incidence of adverse events by treatment group, including major adverse cardiac events (MACE) (death, MI, stroke, coronary revascularization, hospitalization for ACS or heart failure).

E.5.2.1

Timepoint(s) of evaluation of this end point

26 weeks post-randomization

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Evaluate the effect on biomarkers (HDL-C, apoA-I, HDL-subclasses) at various time points

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Argentina

Brazil

European Union

Russian Federation

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

Last patient, Last visit

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1