Safety and Effect of Oral RVX000222 in Subjects With Fabry Disease

November 14, 2023 updated by: Resverlogix Corp

An Open-Label Study to Assess the Safety and Effect on Key Biomarkers of Oral RVX000222 in Subjects With Fabry Disease

Fabry Disease (FD) is a rare X-linked lysosomal storage disorder (LSD) caused by mutations in the GLA gene which translates into decreased activity or lack of function of the enzyme alpha-galactosidase A (α-GAL A) and accumulation of the enzymes substrate, i.e., Gb3, throughout the body. Cardiovascular and renal complications are among the leading causes of death in FD patients. RVX000222 is a BET inhibitor which modulates the expression of a variety of genes and, due to its effects on pathways downstream of substrate accumulation and reduction of major cardiac events, holds promise as a potential add-on therapy to accompany enzyme replacement therapy (ERT) in FD patients.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Fabry Disease (FD) is a rare X-linked lysosomal storage disorder (LSD) caused by mutations in the GLA gene coding for the enzyme alpha-galactosidase A (α-GAL A). As a consequence globotriaosylceramide (Gb3), the enzyme's substrate, is not metabolized efficiently. The result is progressive accumulation of Gb3 and related glycosphinglolipids, particularly in blood vessels of the skin, kidney, heart and brain, causing severe complications such as cardiomyopathy, left ventricular hypertrophy and other cardiovascular related issues, as well as renal failure and end stage renal disease, ischemic stroke and peripheral neuropathy.

RVX000222 is a BET inhibitor which modulates the expression of a variety of genes; in a number of Phase 1 and 2 clinical trials RVX000222 significantly affected markers of cardiovascular disease (CVD), such as high-sensitivity C-reactive protein (hs-CRP), alkaline phosphatase, components of the complement and coagulation cascades, and markers of reverse cholesterol transport in patients with CVD. Due to its beneficial effects on several pathways downstream of Gb3 accumulation and MACE reduction, RVX000222 holds promise as a potential add-on therapy to accompany enzyme replacement therapy (ERT) in FD patients. In addition to regulating disease related pathways, RVX000222 treatment significantly affects putative markers associated with FD such as Afamin and intercellular and vascular adhesion molecules in cell cultures.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Canada
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3H2Y9
        • Queen Elizabeth II Health Sciences Centre, Victoria General Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Subjects who meet the following criteria may be enrolled:

  1. Provide written informed consent before participation in the study.
  2. Aged between 18 and 75 years, inclusive.

  3. Diagnosis of Fabry disease, either

    1. receiving enzyme replacement therapy for at least 6 months at time of screening (Cohort 1).
    2. not receiving enzyme replacement therapy at time of screening and not having received enzyme replacement therapy in the past (Cohort 2).

  4. Female subjects must meet one of the following:

    1. If of childbearing potential, must have a negative urine pregnancy test and must also be willing to practice total abstinence or to use an approved (non-hormonal) form of birth-control throughout the study treatment phase and up to 28 days after the last study drug dose.

      -OR-

    2. Meet at least one of the following criteria:

      • Be postmenopausal, defined as having been amenorrheic for at least 2 years.
      • Have had a hysterectomy or a bilateral oophorectomy.
  5. Male subjects who have not had a vasectomy must practice abstinence or use an approved method of birth control, including barrier contraception, throughout the study treatment phase and up to 3 months after the last study drug dose.

Exclusion Criteria:

Subjects who meet any of the following criteria will not be enrolled:

  1. Patients with stage 5 Chronic Kidney Disease (CKD) receiving renal replacement therapy with either hemodialysis or peritoneal dialysis, renal transplant or with eGFR <15 ml/min/1.73m2.
  2. Patients with prior transplantations of organs or bone marrow.
  3. Patients with unstable cardiac condition including heart attack, stroke, uncontrolled atrial fibrillation or a major cardiac procedure within 3 months.
  4. Current or recent (within 12 months prior to Screening) treatment with cyclosporine.
  5. History of malignancy of any organ system, treated or untreated, within the past 2 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin.
  6. Evidence of cirrhosis from liver imaging or biopsy, a history of hepatic encephalopathy, esophageal or gastric varices, active hepatitis, or prior porta-caval shunt procedure, or a Child-Pugh score of at least 5 points.
  7. Have a screening 12-lead ECG considered clinically significant by the investigator requiring a corrective intervention in the short-term.
  8. Have any known allergy or intolerance to any compound in the test products or any other closely related compound.
  9. ALT or AST >1.5 x ULN at Screen.
  10. Total bilirubin >ULN at Screen.
  11. Use of diclofenac, clavulanic acid or regular use of acetaminophen >1g per day.
  12. Have participated in a clinical study and received any investigational medication within the last 30 days preceding Visit 1 (Screening).
  13. Patients whose safety may be compromised by study participation due to, for example, an infection within the last 30 days.
  14. Are not, in the opinion of the investigator, able or willing to comply with the protocol.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: treatment
RVX000222 (apabetalone) 100 mg to be administered orally BID 12 hours apart.
Drug: RVX000222
oral, BID
Other Names:
  • apabetalone
  • RVX-208

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Adverse events
Time Frame: 16 weeks
Adverse events in Fabry Disease patients from the screening visit until 2 weeks after treatment completion with RVX000222.
16 weeks
Changes in clinical laboratory parameters
Time Frame: 12 weeks
Changes in chemistry and hematology laboratory test results in Fabry Disease patients throughout and at the end of treatment phase with RVX000222 relative to baseline test results.
12 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in Alkaline Phosphatase
Time Frame: 12 weeks
Change in serum alkaline phosphatase in Fabry Disease patients throughout and at the end of treatment phase with RVX000222 relative to baseline level.
12 weeks
Changes in key markers of Chronic Kidney Disease-Bone Mineral Disease (CKD-BMD)
Time Frame: 12 weeks
Changes in key markers of CKD-BMD i.e. RANKL and osteoprotegerin in Fabry Disease patients throughout and at the end of treatment phase with RVX000222 relative to baseline levels.
12 weeks
Changes in key markers of inflammation
Time Frame: 12 weeks
Changes in key markers of inflammation i.e. high-sensitivity C-Reactive Protein (hsCRP) in Fabry Disease patients throughout and at the end of treatment phase with RVX000222 relative to baseline levels.
12 weeks
Changes in markers of alpha-galactosidase (a-GAL A) deficiency
Time Frame: 12 weeks
Changes in key markers of a-GLA A deficiency i.e. Gb3 and lyso-Gb3 in Fabry Disease patients throughout and at the end of treatment phase with RVX000222 relative to baseline level.
12 weeks
Initial uptake and steady-state level of RVX000222
Time Frame: 12 weeks
RVX000222 blood concentration at 4 hours after initial administration in comparison to baseline. Steady-state concentration of RVX000222 and its two principal metabolites, RVX000288 and RVX000404, throughout and at the end of treatment phase with RVX000222.
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Resverlogix Corp

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Michael West, MD, Queen Elizabeth II Health Sciences Centre, Victoria General Site

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 22, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 22, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 22, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 18, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 20, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 25, 2017

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 17, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 14, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • RVX222-CS-020

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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