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

NCT03160430 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: RVX222-CS-018
• Study Type: interventional
• Target: 44
• Locations: 0 countries
• Sites: N/A

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

Keywords

Chronic Kidney Failure; ESRD; End-Stage Kidney Disease; End-Stage Renal Disease; Renal Disease, End-Stage; Renal Failure, Chronic; Renal Failure, End-Stage

Outcome Measures

Primary Outcomes (3)

• 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.

  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

  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

  48 hours

Secondary Outcomes (10)

• Changes in high-sensitivity C-Reactive Protein (hsCRP)

  6 weeks

• Changes in Interleukin-13 (IL-13)

  6 weeks

• Changes in Interleukin-6 (IL-6)

  6 weeks

• Changes in Interleukin-8 (IL-8)

  6 weeks

• Changes in Monocyte Chemoattractant Protein-1 (MCP-1)

  6 weeks

Study Arms (3)

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)

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

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

Drug: apabetalone; Drug: Placebos

Interventions

apabetalone DRUG

RVX000222 oral (apabetalone), 100 mg capsule

Also known as: RVX000222, RVX-208

Part A PK Arm; Part B Sequence A; Part B Sequence B

Placebos DRUG

matching placebo capsule

Also known as: Matching placebo

Part B Sequence A; Part B Sequence B

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Resverlogix Corp: lead

MeSH Terms

Conditions

Kidney Failure, Chronic

Interventions

apabetalone

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Sr. Director of Clinical Operations

CONTACT

403-254-9252; clinicaltrials@resverlogix.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2017
• First Posted: May 19, 2017
• Study Start: November 22, 2024
• Primary Completion (Estimated): November 22, 2026
• Study Completion (Estimated): November 22, 2026
• Last Updated: November 15, 2023

Record last verified: 2023-11