Effect of Harvoni on Proteinuria and eGFR in Hepatitis C Virus Associated Chronic Kidney Disease (CKD)

January 8, 2020 updated by: Raymond Chung, Massachusetts General Hospital

Effect of Ledipasvir and Sofosbuvir on Proteinuria and Estimated Glomerular Filtration Rate in Patients With Early Stage (1-3) Hepatitis C Associated Chronic Kidney Disease

Treatment protocol to see if people with hepatitis C (HCV) and chronic kidney disease (CKD) who are treated with Harvoni for 12 weeks have improvements in their kidney disease.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

The investigators hypothesize that patients with early stage (1-3) CKD caused by HCV infection will have significantly improved proteinuria and eGFR after viral eradication with 12 weeks of treatment Harvoni (LDV/SOF). This trial data will serve as the basis to support further study of LDV/SOF in patients with early CKD. Slowing progression of CKD is a critical goal, as the increasing incidence and prevalence of advanced CKD and end stage renal disease (ESRD) places significant health burden on patients and tremendous costs on our health-care system.

Study Type

Interventional

Enrollment (Actual)

14

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • The subject has signed the written informed consent
  • Male or female ≥ 18 year of age
  • HCV genotype 1 or 4 with ribonucleic acid (HCV RNA) greater than 1000 international units (IU)/milliliter (mL), determined by HCV RNA polymerase chain reaction Roche TaqMan quantitative assay.
  • Initial diagnosis of proteinuric chronic kidney disease occurred < 7 years prior to completion of screening
  • Women of childbearing potential (i.e. women who have not undergone hysterectomy or bilateral oophorectomy, or no medically documented ovarian failure, and are ≤ 50 years of age) must agree to 1 medically approved contraceptive measures and have their partners agree to an additional barrier method of contraception for the duration of the study and for 4 weeks after the last administration of the study drug. Women of childbearing potential must not rely on hormone-containing contraceptive as a form of birth control during the study but may use. An intrauterine device, female barrier methods with cervical cap or diaphragm with spermicidal agent, tubal sterilization, or vasectomy in male partners.
  • Male subjects must agree to consistently and correctly use a condom during heterosexual intercourse and avoid sperm donation for the duration of this study and for 90 days after the last dose of ledipasvir and sofosbuvir. Additionally, if their female partner is of childbearing potential (as defined above), their partner must agree to use either 1 of the non-hormonal methods of birth control listed above or a hormone-containing contraceptive for 90 days after last study drug date. Hormone-containing contraceptive options for partners include implants of levonorgestrel, injectable progesterone, oral contraceptives, contraceptive vaginal ring, or transdermal contraceptive pat
  • Adequate organ function defined as follows platelets ≥ 50 x 109/L; hemoglobin ≥ 9 g/dL, estimated glomerular filtration rate ≥ 30mL/min/1.73m2 as estimated by CKD-Epi equation.
  • Liver imaging to exclude hepatocellular carcinoma (HCC) is required within 6 months in any patient with cirrhosis.
  • Has > 300mg/g creatinine proteinuria on two urine samples obtained within 30 days of starting ledipasvir and sofosbuvir.

Exclusion Criteria:

  • History of evidence of clinically significant disorder other than hepatitis C virus infection or clinically significant laboratory finding that in the investigator's judgment would pose a risk to subject safety, interfere with study procedures, or prevent completion of the study.
  • Pregnant or lactating female
  • Uncontrolled depression or psychiatric disease interfering with the ability to comply with the study procedures or complete the study
  • History or presence of any form of cancer within 3 years prior to enrollment, with the exception of excised basal cell or squamous cell carcinoma of the skin, stage 0 or 1 melanoma, or cervical carcinoma in site or breast carcinoma in situ that has been excised or resected completely and is without evidence of local recurrence or metastasis.
  • Experience life-threatening cryoglobulinemic vasculitis requiring initiation of rituximab, steroids or plasmapheresis.
  • Concomitant use of cimetidine, trimethoprim or other drugs which can increase tubular creatinine reabsorption
  • Uncontrolled cardiovascular or pulmonary disease
  • Uncontrolled hypertension
  • Known HIV infection
  • Known hypersensitivity to ledipasvir or sofosbuvir
  • Prior HCV treatment failure using a medication in the NS5A inhibitor class
  • Individuals who are taking the following medications and require continuation of the medications during the proposed study period will be excluded, given known interactions with ledipasvir-sofosbuvir: Carbamazepine, phenytoin, phenobarbital, oxcarbazepine, rifabutin, rifampin, isoniazid, rifapentine, rosuvastatin, proton pump inhibitors, digoxin, modafinil, and St. John's wort, milk thistle, Echinacea.

  • Having an alternate explanation of chronic kidney disease, including:

    • Diabetic kidney disease, either by biopsy findings or duration of uncontrolled diabetes > 8 years without serologic evidence of immune-complex related kidney disease
    • Chronic hypertensive nephropathy without proteinuria
    • Lupus nephritis
    • Multiple myeloma
    • Obesity related proteinuria, BMI > 35
    • Ongoing nephrotoxic medication use, including NSAIDS
    • Polycystic kidney disease
    • Kidney biopsy showing an alternate explanation for chronic kidney disease

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: 12 weeks treatment with Sofosbuvir/Ledipasvir (400mg/90mg)
10 patients with hepatitis C (HCV) and HCV-associated CKD that will receive 12 weeks treatment with Sofosbuvir/Ledipasvir (400mg/90mg)
Drug: Sofosbuvir/Ledipasvir FDC
12 weeks treatment with Harvoni
Other Names:
  • Harvoni

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Percent Change in Proteinuria
Time Frame: Baseline and 24 weeks (12 weeks after completion of Harvoni)
% change in proteinuria from baseline (timepoint week 0) through timepoint week 24, which was 12 weeks after completion of Harvoni.
Baseline and 24 weeks (12 weeks after completion of Harvoni)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Median Change in eGFR From Baseline to Timepoint Week 24
Time Frame: 24 weeks

Median change from baseline (timepoint week 0) to timepoint week 24, which was 12 weeks after completion of Harvoni.

Median change in eGFR was calculated using the creatinine and cystatin C-based estimating equation.

eGFR = 135 × min(SCr/κ, 1)α × max(SCr/κ, 1)-0.601 × min(Scys/0.8, 1)-0.375 × max(Scys/0.8, 1)-0.711 × 0.995Age × 0.969 [if female] × 1.08 [if black]
24 weeks
Number of Participants With ≥25% Reduction in Proteinuria
Time Frame: 24 weeks
Number of participants with at least -25% change in proteinuria, calculated from baseline (timepoint week 0) to timepoint week 24, which is 12 weeks after completion of Harvoni.
24 weeks
Mean Time in Weeks to Maximum Reduction in Proteinuria
Time Frame: 52 weeks
This outcome evaluated all post-baseline proteinuria values through the 52 week followup, and determined which demonstrated the greatest negative change (reduction) from baseline. We then calculate the mean time to maximum reduction of proteinuria.
52 weeks
Median Change in eGFR From Baseline to Timepoint Week 52
Time Frame: 52 weeks

Median change from baseline (timepoint week 0) to timepoint week 52, which was 40 weeks after completion of Harvoni.

Median change in eGFR was calculated using the creatinine and cystatin C-based estimating equation.

eGFR = 135 × min(SCr/κ, 1)α × max(SCr/κ, 1)-0.601 × min(Scys/0.8, 1)-0.375 × max(Scys/0.8, 1)-0.711 × 0.995Age × 0.969 [if female] × 1.08 [if black]
52 weeks
Change in Urinary β-2microglobulin Levels Before Therapy
Time Frame: 24 weeks

Change in urinary β-2microglobulin levels before therapy with ledipasvir/sofosbuvir fixed dose combination pill.

β-2microglobulin (mcg/L) change prior to initiating HCV-treatment.

This outcome was not assessed.
24 weeks
Change in Urinary β-2microglobulin Levels After Therapy
Time Frame: 24 weeks

Change in urinary β-2microglobulin levels after therapy with ledipasvir/sofosbuvir fixed dose combination pill

β-2microglobulin (mcg/L) levels were assessed at baseline (timepoint week 0) and at timepoint week 24. Change was recorded for each patient, and presented as a median with IQR.
24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Massachusetts General Hospital

Investigators

  • Study Chair: Elizabeth Hohmann, MD, Chair and Physician Director, Partners Human Research Committees

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 15, 2015

Primary Completion (Actual)

September 1, 2017

Study Completion (Actual)

May 1, 2019

Study Registration Dates

First Submitted

July 17, 2015

First Submitted That Met QC Criteria

July 20, 2015

First Posted (Estimate)

July 21, 2015

Study Record Updates

Last Update Posted (Actual)

January 13, 2020

Last Update Submitted That Met QC Criteria

January 8, 2020

Last Verified

January 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IN-US-337-1777

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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