Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    RVX-208 | Fabry Disease
Previous Study | Return to List | Next Study

Safety and Effect of Oral RVX000222 in Subjects With Fabry Disease

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03228940
Recruitment Status : Not yet recruiting
First Posted : July 25, 2017
Last Update Posted : March 26, 2019
Sponsor:
Information provided by (Responsible Party):
Resverlogix Corp

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Fabry Disease Drug: RVX000222 Phase 1 Phase 2

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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Open-label exploratory
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label Study to Assess the Safety and Effect on Key Biomarkers of Oral RVX000222 in Subjects With Fabry Disease
Estimated Study Start Date : September 30, 2019
Estimated Primary Completion Date : September 30, 2020
Estimated Study Completion Date : September 30, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: treatment
RVX000222 (apabetalone) 100 mg to be administered orally BID 12 hours apart.
Drug: RVX000222
oral, BID
Other Names:
  • apabetalone
  • RVX-208




Primary Outcome Measures :
  1. Adverse events [ Time Frame: 16 weeks ]
    Adverse events in Fabry Disease patients from the screening visit until 2 weeks after treatment completion with RVX000222.

  2. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.



Information from the National Library of Medicine

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.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

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): NCT03228940


Contacts
Layout table for location contacts
Contact: Sr. Director Clinical Operations 403-254-9252 clinicaltrials@resverlogix.com

Locations
Layout table for location information
Canada, Nova Scotia
Queen Elizabeth II Health Sciences Centre, Victoria General Site Not yet recruiting
Halifax, Nova Scotia, Canada, B3H2Y9
Contact: Michael West, MD    (902) 473-4023    mwets@dal.ca   
Sponsors and Collaborators
Resverlogix Corp
Investigators
Layout table for investigator information
Principal Investigator: Michael West, MD Queen Elizabeth II Health Sciences Centre, Victoria General Site

Layout table for additonal information
Responsible Party: Resverlogix Corp
ClinicalTrials.gov Identifier: NCT03228940     History of Changes
Other Study ID Numbers: RVX222-CS-020
First Posted: July 25, 2017    Key Record Dates
Last Update Posted: March 26, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
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

Keywords provided by Resverlogix Corp:
Cardiovascular Disease, Renal Disease

Additional relevant MeSH terms:
Layout table for MeSH terms
Fabry Disease
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Cerebral Small Vessel Diseases
Cerebrovascular Disorders
Vascular Diseases
Cardiovascular Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders
Sphingolipidoses
Metabolism, Inborn Errors
Lipidoses
Lipid Metabolism, Inborn Errors