Safety and Effect of Oral RVX000222 in Subjects With Fabry Disease
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|ClinicalTrials.gov Identifier: NCT03228940|
Recruitment Status : Not yet recruiting
First Posted : July 25, 2017
Last Update Posted : March 26, 2019
|Condition or disease||Intervention/treatment||Phase|
|Fabry Disease||Drug: RVX000222||Phase 1 Phase 2|
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 :||Interventional (Clinical Trial)|
|Estimated Enrollment :||16 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Open-label exploratory|
|Masking:||None (Open Label)|
|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|
RVX000222 (apabetalone) 100 mg to be administered orally BID 12 hours apart.
- Adverse events [ Time Frame: 16 weeks ]Adverse events in Fabry Disease patients from the screening visit until 2 weeks after treatment completion with RVX000222.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
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
|Contact: Sr. Director Clinical Operationsemail@example.com|
|Canada, Nova Scotia|
|Queen Elizabeth II Health Sciences Centre, Victoria General Site|
|Halifax, Nova Scotia, Canada, B3H2Y9|
|Contact: Michael West, MD (902) 473-4023 firstname.lastname@example.org|
|Principal Investigator:||Michael West, MD||Queen Elizabeth II Health Sciences Centre, Victoria General Site|