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

NCT02503735 | Terminated Results DMC

• 1 other identifier: IN-US-337-1777
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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.

Conditions

Hepatitis C; Chronic Kidney Disease

Keywords

CKD; HCV

Outcome Measures

Primary Outcomes (1)

• The Percent Change in Proteinuria

  % 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 Outcomes (6)

• Median Change in eGFR From Baseline to Timepoint Week 24

  24 weeks

• Number of Participants With ≥25% Reduction in Proteinuria

  24 weeks

• Mean Time in Weeks to Maximum Reduction in Proteinuria

  52 weeks

• Median Change in eGFR From Baseline to Timepoint Week 52

  52 weeks

• Change in Urinary β-2microglobulin Levels Before Therapy

  24 weeks

Study Arms (1)

12 weeks treatment with Sofosbuvir/Ledipasvir (400mg/90mg)

OTHER

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

Interventions

Sofosbuvir/Ledipasvir FDC DRUG

12 weeks treatment with Harvoni

Also known as: Harvoni

12 weeks treatment with Sofosbuvir/Ledipasvir (400mg/90mg)

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (1)

• 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.

  PMID: 18295055 BACKGROUND

MeSH Terms

Conditions

Hepatitis C; Renal Insufficiency, Chronic

Interventions

Sofosbuvir; ledipasvir, sofosbuvir drug combination

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases; 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

Intervention Hierarchy (Ancestors)

Uridine Monophosphate; Uracil Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides

Results Point of Contact

• Title: Dr. Meghan Sise
• Organization: Massachusetts General Hospital

MSise@partners.org

617-726-5050

Study Officials

• Elizabeth Hohmann, MD

  Chair and Physician Director, Partners Human Research Committees

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Hepatology

Study Record Dates

• First Submitted: July 17, 2015
• First Posted: July 21, 2015
• Study Start: July 15, 2015
• Primary Completion: September 1, 2017
• Study Completion: May 1, 2019
• Last Updated: January 13, 2020
• Results First Posted: January 9, 2020

Record last verified: 2020-01

Locations

US (1)