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.
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 ESRD (end stage renal
disease) places significant health burden on patients and tremendous costs on our health-care
- 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
- 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.
- 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
- Experience life-threatening cryoglobulinemic vasculitis requiring initiation of
rituximab, steroids or plasmapheresis.
- Concomitant use of cimetidine, trimethoprim or other drugs which can increase tubular
- 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
- 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