A Two-Part Phase 2a Study of RVX000222 in Patients With End-Stage Renal Disease Treated With Hemodialysis

NCT ID: NCT03160430

Last Updated: 2023-11-15

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-11-22
• Study Completion Date: 2026-11-22

Brief 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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Part A PK Arm

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)

Group Type: EXPERIMENTAL

apabetalone

Intervention Type: DRUG

RVX000222 oral (apabetalone), 100 mg capsule

Part B Sequence A

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

Group Type: PLACEBO_COMPARATOR

apabetalone

Intervention Type: DRUG

RVX000222 oral (apabetalone), 100 mg capsule

Placebos

Intervention Type: DRUG

matching placebo capsule

Part B Sequence B

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

Group Type: PLACEBO_COMPARATOR

apabetalone

Intervention Type: DRUG

RVX000222 oral (apabetalone), 100 mg capsule

Placebos

Intervention Type: DRUG

matching placebo capsule

Interventions

apabetalone

RVX000222 oral (apabetalone), 100 mg capsule

Intervention Type: DRUG

Placebos

matching placebo capsule

Intervention Type: DRUG

Other Intervention Names

RVX000222; RVX-208; Matching placebo

Eligibility Criteria

Inclusion Criteria

1. Men or women ≥18 and ≤80 years of age.

2. 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.

3. Clinically stable, in the judgment of the investigator.

4. Female subjects must meet one of the following:

1. 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

2. 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.

5. In the view of the investigator, during the course of the trial, subject is expected to:

1. remain on unchanged standard of care medication from 4 weeks prior to Enrollment/Visit 2.

2. not require hospitalization for any condition other than routine hemodialysis.

6. Have given signed informed consent to participate in the study.

Exclusion Criteria

1. Planned major surgery in the next 4 months, including renal transplant, from Enrollment/Visit 2.

2. Major surgery, in the judgement of the investigator, within 12 weeks before enrollment/Visit 2 (excluding vascular access surgery).

3. 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.

4. New York Heart Association (NYHA) Classification, Class III or IV Heart Failure at Screen/Visit 1.

5. Diastolic blood pressure >110 mm Hg or systolic blood pressure >180 mm Hg during screen.

6. Currently receiving antibiotic therapy for systemic infection.

7. In the judgement of the Investigator, evidence of active hepatitis. Hepatitis serology testing will be performed at Screen/Visit 1.

8. 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.

9. Red blood cell (RBC) transfusions within 12 weeks before Enrollment/Visit 2.

10. Current or recent (within 12 months prior to Visit 1) treatment with immunosuppressants (e.g., cyclosporine).

11. Use of fibrates at any dose or niacin/nicotinic acid 250 mg or more within 30 days prior to Screen/Visit 1.

12. Diagnosis of systemic hematologic disease (e.g., sickle cell anemia, myelodysplastic syndromes, hematologic malignancy, myeloma, hemolytic anemia).

13. Hemoglobin <9.5 g/dL at Screen/Visit 1.

14. Alanine aminotransferase (ALT) >1.5 x upper limit of normal (ULN) at Screen/Visit 1.

15. Bilirubin >1.0 x ULN at Screen/Visit 1.

16. Pregnant or breast-feeding women.

17. 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.

18. 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.

19. History of noncompliance with medical regimens or unwillingness to comply with the study protocol.

20. In the judgement of the Investigator, any disorder that may impact the ability to give informed consent for participation in this study.

21. Any condition that, in the opinion of the investigator, would confound the evaluation and interpretation of efficacy and/or safety data.

22. Persons directly involved in the execution of this protocol.

23. 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Resverlogix Corp

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Central Contacts

Sr. Director of Clinical Operations

Role: CONTACT

clinicaltrials@resverlogix.com

403-254-9252

Other Identifiers

RVX222-CS-018

Identifier Type: -

Identifier Source: org_study_id