Fabry DiseasePhase 1/2NCT03228940
Safety and Effect of Oral RVX000222 in Subjects With Fabry Disease
A Phase 1/2 study testing RVX000222 in people with Fabry Disease, run by Resverlogix Corp at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Fabry Disease
- What is being tested?
- RVX000222
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteCanada
- Study dates
- 22 Nov 2022to 22 Nov 2022
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
Canada1 site
Queen Elizabeth II Health Sciences Centre, Victoria General Site
Halifax, Nova Scotia, B3H2Y9
About this study
Official title: 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.
Read the 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.
- Conditions
- Fabry Disease
- Being tested
- RVX000222
- Keywords
- Cardiovascular Disease, Renal Disease
- Medical subject headings
- Fabry Disease, Cardiovascular Diseases, Kidney Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RVX000222Drug
Also called apabetalone, RVX-208
oral, BID
| Study group | Role | What they receive |
|---|---|---|
| treatment | Experimental | RVX000222 (apabetalone) 100 mg to be administered orally BID 12 hours apart. Receives: Drug: RVX000222 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events
Adverse events in Fabry Disease patients from the screening visit until 2 weeks after treatment completion with RVX000222.
Measured: 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.
Measured: 12 weeks
Secondary outcomes (5)
Change in Alkaline Phosphatase
Change in serum alkaline phosphatase in Fabry Disease patients throughout and at the end of treatment phase with RVX000222 relative to baseline level.
Measured: 12 weeks
Changes in key markers of Chronic Kidney Disease-Bone Mineral Disease (CKD-BMD)
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.
Measured: 12 weeks
Changes in key markers of inflammation
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.
Measured: 12 weeks
Changes in markers of alpha-galactosidase (a-GAL A) deficiency
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.
Measured: 12 weeks
Initial uptake and steady-state level of RVX000222
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.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2017
- Study start22 Nov 2022 (estimated)
- Primary completion22 Nov 2022
- Study completion22 Nov 2022
Why it stopped: Changed development priorities
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Fabry DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Open-label exploratory
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Resverlogix Corp
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Michael West, MD, Principal investigator, Queen Elizabeth II Health Sciences Centre, Victoria General Site
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03228940
- Sponsor's protocol ID
- RVX222-CS-020
- Status last verified
- Nov 2023
- First submitted
- 18 Jul 2017
- Last updated
- 18 Nov 2023
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Study to Assess the Safety and Effect on Key Biomarkers of Oral RVX000222 in Subjects With Fabry Disease
- ClinicalTrials.gov ID
- NCT03228940
- Acronym / sponsor ID
- RVX222-CS-020
- Conditions
- Fabry Disease
- Keywords
- Cardiovascular Disease, Renal Disease
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Changed development priorities
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Resverlogix CorpIndustry (pharma, biotech, devices)
- Study start
- 22 Nov 2022 (estimated)
- Primary completion
- 22 Nov 2022 (actual)
- Study completion
- 22 Nov 2022 (actual)
- First posted
- 25 Jul 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open-label exploratory
| Arm | Type | Receives |
|---|---|---|
| treatment | Experimental | Drug: RVX000222RVX000222 (apabetalone) 100 mg to be administered orally BID 12 hours apart. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Provide written informed consent before participation in the study.
- Aged between 18 and 75 years, inclusive.
- Diagnosis of Fabry disease, either
- Female subjects must meet one of the following:
- -OR-
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RVX000222Also: apabetalone, RVX-208oral, BID | Drug | treatment |
Primary outcome
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.
5 secondary outcomes
Change in Alkaline Phosphatase
Time frame: 12 weeks
Changes in key markers of Chronic Kidney Disease-Bone Mineral Disease (CKD-BMD)
Time frame: 12 weeks
Changes in key markers of inflammation
Time frame: 12 weeks
Changes in markers of alpha-galactosidase (a-GAL A) deficiency
Time frame: 12 weeks
Initial uptake and steady-state level of RVX000222
Time frame: 12 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2023.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael West, MD principal investigator
Queen Elizabeth II Health Sciences Centre, Victoria General Site
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing RVX000222 in people with Fabry Disease, run by Resverlogix Corp at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 18 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse events (time frame: 16 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2023.