Safety and Effect of Oral RVX000222 in Subjects With Fabry Disease

NCT03228940 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: RVX222-CS-020
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Fabry Disease

Keywords

Cardiovascular Disease, Renal Disease

Outcome Measures

Primary Outcomes (2)

• Adverse events

  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

  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 Outcomes (5)

• Change in Alkaline Phosphatase

  12 weeks

• Changes in key markers of Chronic Kidney Disease-Bone Mineral Disease (CKD-BMD)

  12 weeks

• Changes in key markers of inflammation

  12 weeks

• Changes in markers of alpha-galactosidase (a-GAL A) deficiency

  12 weeks

• Initial uptake and steady-state level of RVX000222

  12 weeks

Study Arms (1)

treatment

EXPERIMENTAL

RVX000222 (apabetalone) 100 mg to be administered orally BID 12 hours apart.

Drug: RVX000222

Interventions

RVX000222 DRUG

oral, BID

Also known as: apabetalone, RVX-208

treatment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects who meet the following criteria may be enrolled:
• Provide written informed consent before participation in the study.
• Aged between 18 and 75 years, inclusive.
• Diagnosis of Fabry disease, either
• receiving enzyme replacement therapy for at least 6 months at time of screening (Cohort 1).
• not receiving enzyme replacement therapy at time of screening and not having received enzyme replacement therapy in the past (Cohort 2).
• Female subjects must meet one of the following:
• 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-
• 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.
• 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.

You may not qualify if:

• Subjects who meet any of the following criteria will not be enrolled:
• 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.
• Patients with prior transplantations of organs or bone marrow.
• Patients with unstable cardiac condition including heart attack, stroke, uncontrolled atrial fibrillation or a major cardiac procedure within 3 months.
• Current or recent (within 12 months prior to Screening) treatment with cyclosporine.
• 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.
• 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.
• Have a screening 12-lead ECG considered clinically significant by the investigator requiring a corrective intervention in the short-term.
• Have any known allergy or intolerance to any compound in the test products or any other closely related compound.
• ALT or AST \>1.5 x ULN at Screen.
• Total bilirubin \>ULN at Screen.
• Use of diclofenac, clavulanic acid or regular use of acetaminophen \>1g per day.
• Have participated in a clinical study and received any investigational medication within the last 30 days preceding Visit 1 (Screening).
• Patients whose safety may be compromised by study participation due to, for example, an infection within the last 30 days.
• Are not, in the opinion of the investigator, able or willing to comply with the protocol.

Sponsors & Collaborators

• Resverlogix Corp: lead

Study Sites (1)

Queen Elizabeth II Health Sciences Centre, Victoria General Site

Halifax, Nova Scotia, B3H2Y9, Canada

Location

MeSH Terms

Conditions

Fabry Disease; Cardiovascular Diseases; Kidney Diseases

Interventions

apabetalone

Condition Hierarchy (Ancestors)

Sphingolipidoses; 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; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Michael West, MD

  Queen Elizabeth II Health Sciences Centre, Victoria General Site

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open-label exploratory

Study Record Dates

• First Submitted: July 18, 2017
• First Posted: July 25, 2017
• Study Start: November 22, 2022
• Primary Completion: November 22, 2022
• Study Completion: November 22, 2022
• Last Updated: November 18, 2023

Record last verified: 2023-11

Locations

CA (1)