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Effects of Ledipasvir/Sofosbuvir on the Pharmacokinetics and Renal Safety of Tenofovir Alafenamide (TAF)

Primary Purpose

Hepatitis C, HIV Coinfection

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

TDF with a boosted protease inhibitor

TAF with a boosted protease inhibitor

TAF with a boosted protease inhibitor and LDV/SOF

About this trial

This is an interventional other trial for Hepatitis C

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Between 18-70 years of age
Have been taking TDF and a ritonavir- or cobicistat-boosted protease inhibitor as part of standard care for treatment of HIV

Exclusion Criteria:

eGFR < 30 mL/min
Pregnant or planning pregnancy
Breastfeeding
Any medical, social, or mental-health issue(s) that, in the opinion of the investigators, could interfere with study participation or the study outcomes
Signs or symptoms of decompensated liver disease
Hepatitis B infection
Medications that may cause unwanted drug interactions with ledipasvir/sofosbuvir or emtricitabine/tenofovir alafenamide
Unwillingness or inability to comply with study procedures
Chronic hepatitis C infection

Sites / Locations

University of Colorado Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

TAF with a boosted PI and LDV/SOF

Arm Description

Participants who are already taking tenofovir disoproxil fumarate 300 mg (in the form of Viread or Truvada) in combination with either a ritonavir- or cobicistat-boosted protease inhibitor for HIV treatment will continue to take their prescribed treatment for 12 weeks after enrollment. Participants will be switched from tenofovir disoproxil fumarate to tenofovir alafenamide (TAF) 25 mg/emtricitabine (FTC) 200 mg (Descovy) with a boosted protease inhibitor for the next 12 weeks. After taking TAF/FTC for 12 weeks, participants will then start taking ledipasvir 90mg/sofosbuvir 400mg (LDV/SOV, Harvoni) in combination with TAF/FTC and a boosted protease inhibitor for 4 weeks. Participants will then return to taking TAF/FTC with a boosted protease inhibitor for the final 12 weeks of the study.

Outcomes

Primary Outcome Measures

Change From Week 12 Plasma Tenofovir Area Under the Plasma Concentration vs. Time Curve From Time 0 to 24 Hours (AUC0-24) at 24 and 28 Weeks

Compare plasma tenofovir AUC0-24 between TAF with boosted PI vs. TDF with boosted PI (Phase 2 vs. 1), and between TAF with boosted PI and LDV/SOF vs. TDF with boosted PI (Phase 3 vs. 1)

Change From Week 12 Tenofovir-diphosphate (TFV-DP) in Peripheral Blood Mononuclear Cells (PBMCs) at 24 and 28 Weeks

Compare tenofovir-diphosphate (TFV-DP) in peripheral blood mononuclear cells (PBMCs) between TAF with a boosted PI vs. TDF with a boosted PI (Phase 2 vs. 1), and TAF with a boosted PI and LDV/SOF vs. TDF with a boosted PI (Phase 3 vs. 1).

Secondary Outcome Measures

Change From Week 12 Tenofovir-diphosphate (TFV-DP) in Dried Blood Spots (DBS)

Compare tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) between TAF with a boosted PI vs. TDF with a boosted PI (Phase 2 vs. 1), and TAF with a boosted PI and LDV/SOF vs. TDF with a boosted PI (Phase 3 vs. 1)

Change in Estimated Glomerular Filtration Rate (eGFR) and Renal Biomarkers: eGFR

Change in estimated glomerular filtration rate (eGFR)

Change in Estimated Glomerular Filtration Rate (eGFR) and Renal Biomarkers: UPCR

Change in estimated glomerular filtration rate (eGFR) and renal biomarkers: Urine protein to creatinine ratio (UPCR)

Change in Estimated Glomerular Filtration Rate (eGFR) and Renal Biomarkers: B2M/Cr Ratio, and RBP/Cr Ratio

Change in renal biomarkers: urinary beta-2 microglobulin (B2M)/creatinine (Cr) ratio, and urinary retinol binding protein (RBP)/Cr ratio

Full Information

NCT ID

NCT03126370

First Posted

April 19, 2017

Last Updated

January 21, 2021

Sponsor

University of Colorado, Denver

1. Study Identification

Unique Protocol Identification Number

NCT03126370

Brief Title

Effects of Ledipasvir/Sofosbuvir on the Pharmacokinetics and Renal Safety of Tenofovir Alafenamide (TAF)

Official Title

Effects of Ledipasvir/Sofosbuvir Treatment on the Pharmacokinetics and Renal Safety of Tenofovir Alafenamide (TAF) in Patients With HIV.

Study Type

Interventional

2. Study Status

Record Verification Date

January 2021

Overall Recruitment Status

Completed

Study Start Date

January 8, 2018 (Actual)

Primary Completion Date

July 12, 2019 (Actual)

Study Completion Date

October 1, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Colorado, Denver

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

Brief Summary

This study will evaluate the effect of ledipasvir/sofosbuvir (LDV/SOF) treatment on the pharmacokinetics (PK) and renal safety of tenofovir in the form of tenofovir alafenamide (TAF). Subjects living with human immunodeficiency virus (HIV) who are receiving tenofovir-based antiretroviral therapy (in the form of tenofovir disoproxil fumarate [TDF]), and are also taking a ritonavir- or cobicistat-boosted protease inhibitor will be invited to participate. The study will consist of five visits: a screening visit, three abbreviated 4-hour pharmacokinetic visits, and one end-of-study follow-up visit. Subjects will also be asked to use a Wisepill device, which will track medication adherence throughout the study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatitis C, HIV Coinfection

7. Study Design

Primary Purpose

Other

Study Phase

Phase 4

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

10 (Actual)

8. Arms, Groups, and Interventions

Arm Title

TAF with a boosted PI and LDV/SOF

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

TDF with a boosted protease inhibitor

Other Intervention Name(s)

Viread or Truvada with a boosted protease inhibitor

Intervention Description

Intervention Type

Drug

Intervention Name(s)

TAF with a boosted protease inhibitor

Other Intervention Name(s)

Descovy with a boosted protease inhibitor

Intervention Description

Participants will be switched from tenofovir disoproxil fumarate to tenofovir alafenamide 25 mg/emtricitabine 200 mg with a boosted protease inhibitor. Other: Blood draws for tenofovir PK, renal function assessment

Intervention Type

Drug

Intervention Name(s)

TAF with a boosted protease inhibitor and LDV/SOF

Other Intervention Name(s)

Descovy with a boosted protease inhibitor and Harvoni

Intervention Description

After taking tenofovir alafenamide/emtricitabine for 12 weeks, participants will then start taking ledipasvir 90 mg/sofosbuvir 400 mg (Harvoni) in combination with the tenofovir alafenamide 25 mg/emtricitabine 200 mg (Descovy) and a boosted protease inhibitor for 4 weeks. Subjects will then return to taking tenofovir alafenamide 25 mg/emtricitabine 200 mg (Descovy) and a boosted protease inhibitor for the final 12 weeks. Other: Blood draws for tenofovir PK, renal function assessment

Primary Outcome Measure Information:

Title

Change From Week 12 Plasma Tenofovir Area Under the Plasma Concentration vs. Time Curve From Time 0 to 24 Hours (AUC0-24) at 24 and 28 Weeks

Description

Compare plasma tenofovir AUC0-24 between TAF with boosted PI vs. TDF with boosted PI (Phase 2 vs. 1), and between TAF with boosted PI and LDV/SOF vs. TDF with boosted PI (Phase 3 vs. 1)

Time Frame

12 weeks and 24 weeks and 28 weeks

Title

Change From Week 12 Tenofovir-diphosphate (TFV-DP) in Peripheral Blood Mononuclear Cells (PBMCs) at 24 and 28 Weeks

Description

Time Frame

12 weeks, and 24 weeks and 28 weeks

Secondary Outcome Measure Information:

Title

Change From Week 12 Tenofovir-diphosphate (TFV-DP) in Dried Blood Spots (DBS)

Description

Time Frame

12 weeks and 24 and 28 weeks

Title

Change in Estimated Glomerular Filtration Rate (eGFR) and Renal Biomarkers: eGFR

Description

Change in estimated glomerular filtration rate (eGFR)

Time Frame

12 weeks, 24 weeks, and 28 weeks

Title

Change in Estimated Glomerular Filtration Rate (eGFR) and Renal Biomarkers: UPCR

Description

Change in estimated glomerular filtration rate (eGFR) and renal biomarkers: Urine protein to creatinine ratio (UPCR)

Time Frame

12 weeks, 24 weeks, and 28 weeks

Title

Change in Estimated Glomerular Filtration Rate (eGFR) and Renal Biomarkers: B2M/Cr Ratio, and RBP/Cr Ratio

Description

Change in renal biomarkers: urinary beta-2 microglobulin (B2M)/creatinine (Cr) ratio, and urinary retinol binding protein (RBP)/Cr ratio

Time Frame

12 weeks, 24 weeks, and 28 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Between 18-70 years of age Have been taking TDF and a ritonavir- or cobicistat-boosted protease inhibitor as part of standard care for treatment of HIV Exclusion Criteria: eGFR < 30 mL/min Pregnant or planning pregnancy Breastfeeding Any medical, social, or mental-health issue(s) that, in the opinion of the investigators, could interfere with study participation or the study outcomes Signs or symptoms of decompensated liver disease Hepatitis B infection Medications that may cause unwanted drug interactions with ledipasvir/sofosbuvir or emtricitabine/tenofovir alafenamide Unwillingness or inability to comply with study procedures Chronic hepatitis C infection

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jennifer J Kiser, PharmD

Organizational Affiliation

University of Colorado, Denver

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Colorado Hospital

City

Aurora

State/Province

Colorado

ZIP/Postal Code

80045

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

Not Applicable. As per the question above, we do not plan to share IPD

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Effects of Ledipasvir/Sofosbuvir on the Pharmacokinetics and Renal Safety of Tenofovir Alafenamide (TAF)

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