Hepatitis CNCT02503735
Effect of Harvoni on Proteinuria and eGFR in Hepatitis C Virus Associated Chronic Kidney Disease (CKD)
A study testing Sofosbuvir/Ledipasvir FDC in people with Hepatitis C and Chronic Kidney Disease, run by Massachusetts General Hospital at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatitis C, Chronic Kidney Disease
- What is being tested?
- Sofosbuvir/Ledipasvir FDC
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Jul 2015to May 2019
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
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
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.
Read the 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.
- Conditions
- Hepatitis C, Chronic Kidney Disease
- Being tested
- Sofosbuvir/Ledipasvir FDC
- Keywords
- CKD, HCV
- Medical subject headings
- Hepatitis C, Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sofosbuvir/Ledipasvir FDCDrug
Also called Harvoni
12 weeks treatment with Harvoni
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: Drug: Sofosbuvir/Ledipasvir FDC |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and 24 weeks (12 weeks after completion of Harvoni)
Secondary outcomes (6)
Median Change in eGFR From Baseline to Timepoint Week 24
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]
Measured: 24 weeks
Number of Participants With ≥25% Reduction in Proteinuria
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.
Measured: 24 weeks
Mean Time in Weeks to Maximum Reduction in Proteinuria
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.
Measured: 52 weeks
Median Change in eGFR From Baseline to Timepoint Week 52
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]
Measured: 52 weeks
Change in Urinary β-2microglobulin Levels Before Therapy
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.
Measured: 24 weeks
Change in Urinary β-2microglobulin Levels After Therapy
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.
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2015 (estimated)
- Study start15 Jul 2015
- Primary completionSep 2017
- Study completionMay 2019
Why it stopped: Unable to meet enrollment goal
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hepatitis CStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Raymond Chung, Massachusetts General Hospital
- Investigators
- Elizabeth Hohmann, MD, Study chair, Chair and Physician Director, Partners Human Research Committees
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02503735
- Sponsor's protocol ID
- IN-US-337-1777
- Status last verified
- Jan 2020
- First submitted
- 17 Jul 2015
- Last updated
- 13 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 18295055
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02503735
- Acronym / sponsor ID
- IN-US-337-1777
- Conditions
- Hepatitis C, Chronic Kidney Disease
- Keywords
- CKD, HCV
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Unable to meet enrollment goal
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- 15 Jul 2015 (actual)
- Primary completion
- Sep 2017 (actual)
- Study completion
- May 2019 (actual)
- First posted
- 21 Jul 2015 (estimated)
- Results
- Posted 9 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 12 weeks treatment with Sofosbuvir/Ledipasvir (400mg/90mg) | Other | Drug: Sofosbuvir/Ledipasvir FDC10 patients with hepatitis C (HCV) and HCV-associated CKD that will receive 12 weeks treatment with Sofosbuvir/Ledipasvir (400mg/90mg) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (21 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sofosbuvir/Ledipasvir FDCAlso: Harvoni12 weeks treatment with Harvoni | Drug | 12 weeks treatment with Sofosbuvir/Ledipasvir (400mg/90mg) |
Primary outcome
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.
6 secondary outcomes
Median Change in eGFR From Baseline to Timepoint Week 24
Time frame: 24 weeks
Number of Participants With ≥25% Reduction in Proteinuria
Time frame: 24 weeks
Mean Time in Weeks to Maximum Reduction in Proteinuria
Time frame: 52 weeks
Median Change in eGFR From Baseline to Timepoint Week 52
Time frame: 52 weeks
Change in Urinary β-2microglobulin Levels Before Therapy
Time frame: 24 weeks
Change in Urinary β-2microglobulin Levels After Therapy
Time frame: 24 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 18295055Stevens 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elizabeth Hohmann, MD study chair
Chair and Physician Director, Partners Human Research Committees
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Sofosbuvir/Ledipasvir FDC in people with Hepatitis C and Chronic Kidney Disease, run by Massachusetts General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Percent Change in Proteinuria (time frame: Baseline and 24 weeks (12 weeks after completion of Harvoni)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02503735, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jan 2020.