Kidney Failure, ChronicPhase 1/2NCT03160430
A Two-Part Phase 2a Study of RVX000222 in Patients With End-Stage Renal Disease Treated With Hemodialysis
A Phase 1/2 study testing apabetalone in people with Kidney Failure, Chronic, run by Resverlogix Corp.
Trial summary
This is a multi-center, two-part study; Part A and Part B. Part A of the study is an open-label, single-dose pharmacokinetic (PK) evaluation of 100 mg RVX000222 on dialysis and non-dialysis days in eight (8) End Stage Renal Disease (ESRD) patients who receive hemodialysis as standard of care. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Kidney Failure, Chronic
- What is being tested?
- apabetalone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- No sites listed yet
- Study dates
- 22 Nov 2024to 22 Nov 2026
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men or women ≥18 and ≤80 years of age.
- Diagnosis of end-stage renal disease and receiving hemodialysis an average of three (3) times per week for at least ninety (90) days prior to Enrollment/Visit 2.
- Clinically stable, in the judgment of the investigator.
- Female subjects must meet one of the following:
- If of childbearing potential, must have a negative serum pregnancy test and be willing and able to use medically acceptable non-hormonal method of birth control (non-hormonal intrauterine device, condom, or diaphragm) or remain abstinent from Screen until Follow-up Visit, or
- Be of non-child-bearing potential: post-surgical sterilization (hysterectomy or a bilateral oophorectomy) or post-menopausal. Post-menopausal is defined as amenorrhea for ≥2 years at Screen/Visit 1.
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- In the view of the investigator, during the course of the trial, subject is expected to:
- remain on unchanged standard of care medication from 4 weeks prior to Enrollment/Visit 2.
- not require hospitalization for any condition other than routine hemodialysis.
- Have given signed informed consent to participate in the study.
Who cannot join
- Planned major surgery in the next 4 months, including renal transplant, from Enrollment/Visit 2.
- Major surgery, in the judgement of the investigator, within 12 weeks before enrollment/Visit 2 (excluding vascular access surgery).
- Hospitalization for congestive heart failure, myocardial infarction, deep vein thrombosis, stroke or transient ischemic attack or peripheral arterial disease within 6 months before Enrollment/Visit 2.
- New York Heart Association (NYHA) Classification, Class III or IV Heart Failure at Screen/Visit 1.
- Diastolic blood pressure >110 mm Hg or systolic blood pressure >180 mm Hg during screen.
- Currently receiving antibiotic therapy for systemic infection.
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- In the judgement of the Investigator, evidence of active hepatitis. Hepatitis serology testing will be performed at Screen/Visit 1.
- 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.
- Red blood cell (RBC) transfusions within 12 weeks before Enrollment/Visit 2.
- Current or recent (within 12 months prior to Visit 1) treatment with immunosuppressants (e.g., cyclosporine).
- Use of fibrates at any dose or niacin/nicotinic acid 250 mg or more within 30 days prior to Screen/Visit 1.
- Diagnosis of systemic hematologic disease (e.g., sickle cell anemia, myelodysplastic syndromes, hematologic malignancy, myeloma, hemolytic anemia).
- Hemoglobin <9.5 g/dL at Screen/Visit 1.
- Alanine aminotransferase (ALT) >1.5 x upper limit of normal (ULN) at Screen/Visit 1.
- Bilirubin >1.0 x ULN at Screen/Visit 1.
- Pregnant or breast-feeding women.
- Any condition which, in the opinion of the investigator, may place the subject at higher risk from his/her participation in the study, or is likely to prevent the subject from complying with the requirements of the study or completing the study.
- Treatment with an investigational agent or device within 30 days or 5 half-lives before Enrollment/Visit 2 or scheduled to receive an investigational agent other than those specified by this protocol during the course of this study.
- History of noncompliance with medical regimens or unwillingness to comply with the study protocol.
- In the judgement of the Investigator, any disorder that may impact the ability to give informed consent for participation in this study.
- Any condition that, in the opinion of the investigator, would confound the evaluation and interpretation of efficacy and/or safety data.
- Persons directly involved in the execution of this protocol.
- Are unwilling to abstain from alcoholic beverages, caffeine or xanthine-containing products (e.g., tea, coffee, chocolate, cola), and use of nicotine products from 24 hours prior to Clinical Research Unit (CRU) admission to 48 hours post RVX000222 dose administration.
- 23. Parathyroid hormone, intact (PTH, intact) <150 pg/mL or >800 pg/mL at Screen/Visit 1.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: A Two-Part Phase 2a Study in Patients With End-Stage Renal Disease Treated With Hemodialysis; Part A is an Open-Label Study Arm to Evaluate the Effect of Hemodialysis on the Pharmacokinetics of 100 mg RVX000222; and Part B is a Double-Blind, Randomized, Placebo-Controlled, Sequential Cross-Over Study Arm to Evaluate the Efficacy, Safety, and Pharmacokinetics of RVX000222
This is a multi-center, two-part study; Part A and Part B. Part A of the study is an open-label, single-dose pharmacokinetic (PK) evaluation of 100 mg RVX000222 on dialysis and non-dialysis days in eight (8) End Stage Renal Disease (ESRD) patients who receive hemodialysis as standard of care.
Part B of the study is a double-blind, placebo-controlled study in up to thirty six (36) ESRD patients receiving hemodialysis using a sequential cross-over design with RVX000222 at a daily oral dose of 100 mg b.i.d. (200 mg per day) or matching placebo in combination with SoC.
The primary objective of the study is to evaluate if treatment with RVX000222 in combination with standard of care (SoC) decreases plasma alkaline phosphatase in comparison to placebo and SoC.
- Conditions
- Kidney Failure, Chronic
- Being tested
- apabetalone, Placebos
- Keywords
- Chronic Kidney Failure, ESRD, End-Stage Kidney Disease, End-Stage Renal Disease, Renal Disease, End-Stage, Renal Failure, Chronic, Renal Failure, End-Stage
- Medical subject headings
- Kidney Failure, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
apabetaloneDrug
Also called RVX000222, RVX-208
RVX000222 oral (apabetalone), 100 mg capsule
PlacebosDrug
Also called Matching placebo
matching placebo capsule
| Study group | Role | What they receive |
|---|---|---|
| Part A PK Arm | Experimental | a single 100 mg dose of RVX000222 (apabetalone) on the day of dialysis, followed by a one (1) week washout period, and a second dose of RVX000222 (apabetalone) administered on a non-dialysis day (total of two (2) 100 mg RVX000222 doses) Receives: Drug: apabetalone |
| Part B Sequence A | Placebo comparator | RVX000222 (apabetalone) 100 mg b.i.d (total 200 mg/day) for 6 weeks; 4 Week Washout (No RVX000222/placebo administration); Placebo b.i.d for 6 weeks Receives: Drug: apabetalone; Drug: Placebos |
| Part B Sequence B | Placebo comparator | Placebo b.i.d for 6 weeks; 4 Week Washout (No RVX000222/placebo administration); RVX000222 (apabetalone) 100 mg b.i.d (total 200 mg/day) for 6 weeks Receives: Drug: apabetalone; Drug: Placebos |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent change in alkaline phosphatase (ALP) concentration (Part B)
The primary endpoint of the study is the comparison of the RVX000222 treatment period to the placebo period in the percent change in ALP concentration. Percent change is computed relative to the beginning of each period.
Measured: Percent change is computed relative to the beginning of each period (6 weeks)
Single Dose Cmax of RVX000222 (apabetalone) and the Metabolites RVX000288 and RVX000404
Primary PK comparison between dialysis (test) and non-dialysis (reference) days for Cmax of RVX000222 and its two principal metabolites, RVX000288 and RVX000404
Measured: 48 hours
Single Dose AUC of RVX000222 (apabetalone) and the Metabolites RVX000288 and RVX000404
Primary PK comparison between dialysis (test) and non-dialysis (reference) days for AUC of RVX000222 and its two principal metabolites, RVX000288 and RVX000404
Measured: 48 hours
Secondary outcomes (10)
Changes in high-sensitivity C-Reactive Protein (hsCRP)
Changes in hsCRP in dialysis patients at the end of the RVX000222 treatment period relative to the end of the placebo period
Measured: 6 weeks
Changes in Interleukin-13 (IL-13)
Changes in IL-13 in dialysis patients at the end of the RVX000222 treatment period relative to the end of the placebo period
Measured: 6 weeks
Changes in Interleukin-6 (IL-6)
Changes in IL-6 in dialysis patients at the end of the RVX000222 treatment period relative to the end of the placebo period
Measured: 6 weeks
Changes in Interleukin-8 (IL-8)
Changes in IL-8 in dialysis patients at the end of the RVX000222 treatment period relative to the end of the placebo period
Measured: 6 weeks
Changes in Monocyte Chemoattractant Protein-1 (MCP-1)
Changes in MCP-1 in dialysis patients at the end of the RVX000222 treatment period relative to the end of the placebo period
Measured: 6 weeks
Change in key markers of vascular mineralization
Change in key markers of vascular mineralization i.e. RANKL and osteoprotegerin at the end of the RVX000222 treatment period relative to the end of the placebo period
Measured: 6 weeks
Changes in ALP isoenzymes
Changes in ALP isoenzymes at the end of the RVX000222 treatment period relative to the end of the placebo period
Measured: 6 weeks
Changes in Parathyroid hormone (PTH)
Changes in parathyroid hormone at the end of the RVX000222 treatment period relative to the end of the placebo period
Measured: 6 weeks
Change in apolipoprotein A1 (apoA-I), HDL-C, LDL-C, apolipoprotein B (apoB), and triglycerides
Change in apoA-I, HDL-C, LDL-C, apoB, and triglycerides at the end of the RVX000222 treatment period relative to the end of the placebo period
Measured: 6 weeks
Change in Analyzing Data, Recognizing Excellence and Optimizing Outcomes All-Cause Mortality Risk Score For Patients on Chronic Hemodialysis (ARO Score)
Change in ARO Score at the end of the RVX000222 treatment period relative to the end of the placebo period
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2017
- Study start22 Nov 2024 (estimated)
- Primary completion22 Nov 2026 (estimated)
- Study completion22 Nov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Kidney Failure, ChronicStudies 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
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 44 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Resverlogix Corp
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03160430
- Sponsor's protocol ID
- RVX222-CS-018
- Status last verified
- Nov 2023
- First submitted
- 16 May 2017
- Last updated
- 15 Nov 2023
- Results posted
- No
- Data monitoring committee
- 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 15 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Two-Part Phase 2a Study in Patients With End-Stage Renal Disease Treated With Hemodialysis; Part A is an Open-Label Study Arm to Evaluate the Effect of Hemodialysis on the Pharmacokinetics of 100 mg RVX000222; and Part B is a Double-Blind, Randomized, Placebo-Controlled, Sequential Cross-Over Study Arm to Evaluate the Efficacy, Safety, and Pharmacokinetics of RVX000222
- ClinicalTrials.gov ID
- NCT03160430
- Acronym / sponsor ID
- RVX222-CS-018
- Conditions
- Kidney Failure, Chronic
- Keywords
- Chronic Kidney Failure, ESRD, End-Stage Kidney Disease, End-Stage Renal Disease, Renal Disease, End-Stage, Renal Failure, Chronic, Renal Failure, End-Stage
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 44 participants (estimated)
- Lead sponsor
- Resverlogix CorpIndustry (pharma, biotech, devices)
- Study start
- 22 Nov 2024 (estimated)
- Primary completion
- 22 Nov 2026 (estimated)
- Study completion
- 22 Nov 2026 (estimated)
- First posted
- 19 May 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.
This is a multi-center, two-part study; Part A and Part B. Part A of the study is an open-label, single-dose pharmacokinetic (PK) evaluation of 100 mg RVX000222 on dialysis and non-dialysis days in eight (8) End Stage Renal Disease (ESRD) patients who receive hemodialysis as standard of care.
Part B of the study is a double-blind, placebo-controlled study in up to thirty six (36) ESRD patients receiving hemodialysis using a sequential cross-over design with RVX000222 at a daily oral dose of 100 mg b.i.d. (200 mg per day) or matching placebo in combination with SoC.
The primary objective of the study is to evaluate if treatment with RVX000222 in combination with standard of care (SoC) decreases plasma alkaline phosphatase in comparison to placebo and SoC.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Part A PK Arm | Experimental | Drug: apabetalonea single 100 mg dose of RVX000222 (apabetalone) on the day of dialysis, followed by a one (1) week washout period, and a second dose of RVX000222 (apabetalone) administered on a non-dialysis day (total of two (2) 100 mg RVX000222 doses) |
| Part B Sequence A | Placebo comparator | Drug: apabetalone, Drug: PlacebosRVX000222 (apabetalone) 100 mg b.i.d (total 200 mg/day) for 6 weeks; 4 Week Washout (No RVX000222/placebo administration); Placebo b.i.d for 6 weeks |
| Part B Sequence B | Placebo comparator | Drug: apabetalone, Drug: PlacebosPlacebo b.i.d for 6 weeks; 4 Week Washout (No RVX000222/placebo administration); RVX000222 (apabetalone) 100 mg b.i.d (total 200 mg/day) for 6 weeks |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Men or women ≥18 and ≤80 years of age.
- Diagnosis of end-stage renal disease and receiving hemodialysis an average of three (3) times per week for at least ninety (90) days prior to Enrollment/Visit 2.
- Clinically stable, in the judgment of the investigator.
- Female subjects must meet one of the following:
- In the view of the investigator, during the course of the trial, subject is expected to:
Key exclusion criteria (24 listed)
- Planned major surgery in the next 4 months, including renal transplant, from Enrollment/Visit 2.
- Major surgery, in the judgement of the investigator, within 12 weeks before enrollment/Visit 2 (excluding vascular access surgery).
- Hospitalization for congestive heart failure, myocardial infarction, deep vein thrombosis, stroke or transient ischemic attack or peripheral arterial disease within 6 months before Enrollment/Visit 2.
- New York Heart Association (NYHA) Classification, Class III or IV Heart Failure at Screen/Visit 1.
- Diastolic blood pressure >110 mm Hg or systolic blood pressure >180 mm Hg during screen.
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 |
|---|---|---|
| apabetaloneAlso: RVX000222, RVX-208RVX000222 oral (apabetalone), 100 mg capsule | Drug | Part A PK Arm, Part B Sequence A, Part B Sequence B |
| PlacebosAlso: Matching placebomatching placebo capsule | Drug | Part B Sequence A, Part B Sequence B |
Primary outcome
Percent change in alkaline phosphatase (ALP) concentration (Part B)
Time frame: Percent change is computed relative to the beginning of each period (6 weeks)
The primary endpoint of the study is the comparison of the RVX000222 treatment period to the placebo period in the percent change in ALP concentration. Percent change is computed relative to the beginning of each period.
Single Dose Cmax of RVX000222 (apabetalone) and the Metabolites RVX000288 and RVX000404
Time frame: 48 hours
Primary PK comparison between dialysis (test) and non-dialysis (reference) days for Cmax of RVX000222 and its two principal metabolites, RVX000288 and RVX000404
Single Dose AUC of RVX000222 (apabetalone) and the Metabolites RVX000288 and RVX000404
Time frame: 48 hours
Primary PK comparison between dialysis (test) and non-dialysis (reference) days for AUC of RVX000222 and its two principal metabolites, RVX000288 and RVX000404
10 secondary outcomes
Changes in high-sensitivity C-Reactive Protein (hsCRP)
Time frame: 6 weeks
Changes in Interleukin-13 (IL-13)
Time frame: 6 weeks
Changes in Interleukin-6 (IL-6)
Time frame: 6 weeks
Changes in Interleukin-8 (IL-8)
Time frame: 6 weeks
Changes in Monocyte Chemoattractant Protein-1 (MCP-1)
Time frame: 6 weeks
Change in key markers of vascular mineralization
Time frame: 6 weeks
Changes in ALP isoenzymes
Time frame: 6 weeks
Changes in Parathyroid hormone (PTH)
Time frame: 6 weeks
Change in apolipoprotein A1 (apoA-I), HDL-C, LDL-C, apolipoprotein B (apoB), and triglycerides
Time frame: 6 weeks
Change in Analyzing Data, Recognizing Excellence and Optimizing Outcomes All-Cause Mortality Risk Score For Patients on Chronic Hemodialysis (ARO Score)
Time frame: 6 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 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.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing apabetalone in people with Kidney Failure, Chronic, run by Resverlogix Corp.
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 10 inclusion and 24 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: opening soon, as of the sponsor's last update on 15 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Sr. Director of Clinical Operations (403-254-9252, clinicaltrials@resverlogix.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent change in alkaline phosphatase (ALP) concentration (Part B) (time frame: Percent change is computed relative to the beginning of each period (6 weeks)). The study lists 3 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 15 Nov 2023.