Clinical trial NCT02503735: Effect of Harvoni on Proteinuria and eGFR in Hepatitis C Virus Associated Chronic Kidney Disease (CKD)
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Hepatitis C
Chronic Kidney Disease
Keywords: CKD
HCV
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2015-07-21
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: The Percent Change in Proteinuria
timeFrame: Baseline and 24 weeks (12 weeks after completion of Harvoni)
Secondary outcomes:
measure: Median Change in eGFR From Baseline to Timepoint Week 24
timeFrame: 24 weeks
measure: Number of Participants With ≥25% Reduction in Proteinuria
timeFrame: 24 weeks
measure: Mean Time in Weeks to Maximum Reduction in Proteinuria
timeFrame: 52 weeks
measure: Median Change in eGFR From Baseline to Timepoint Week 52
timeFrame: 52 weeks
measure: Change in Urinary β-2microglobulin Levels Before Therapy
timeFrame: 24 weeks
measure: Change in Urinary β-2microglobulin Levels After Therapy
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Chair and Physician Director, Partners Human Research Committees
name: Elizabeth Hohmann, MD
role: STUDY_CHAIR
References:
citation: Stevens LA, Coresh J, Schmid CH, Feldman HI, Froissart M, Kusek J, Rossert J, Van Lente F, Bruce RD 3rd, Zhang YL, Greene T, Levey AS. Estimating GFR using serum cystatin C alone and in combination with serum creatinine: a pooled analysis of 3,418 individuals with CKD. Am J Kidney Dis. 2008 Mar;51(3):395-406. doi: 10.1053/j.ajkd.2007.11.018.