Trial Outcomes & Findings for Effect of Harvoni on Proteinuria and eGFR in Hepatitis C Virus Associated Chronic Kidney Disease (CKD) (NCT NCT02503735)

NCT ID: NCT02503735

Last Updated: 2020-01-13

Results Overview

% change in proteinuria from baseline (timepoint week 0) through timepoint week 24, which was 12 weeks after completion of Harvoni.

• Recruitment status: TERMINATED
• Study phase: NA
• Target enrollment: 14 participants
• Primary outcome timeframe: Baseline and 24 weeks (12 weeks after completion of Harvoni)
• Results posted on: 2020-01-13

Participant Flow

14 patients were recruited and signed informed consent

Participant milestones

Measure	12 Weeks Treatment With Sofosbuvir/Ledipasvir (400mg/90mg) Sofosbuvir/Ledipasvir FDC: 12 weeks treatment with Harvoni (10 total dosed on protocol)
Overall Study STARTED	10
Overall Study SVR 12 (12week Post Treatment RNA Neg)	8
Overall Study COMPLETED	10
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	12 Weeks Treatment With Sofosbuvir/Ledipasvir (400mg/90mg) n=10 Participants Sofosbuvir/Ledipasvir (400mg/90mg) FDC: 12 weeks treatment with Harvoni for patients with Hepatitis C (HCV) and HCV-associated CKD Subjects were followed for one year after treatment initiation
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=5 Participants
Age, Categorical >=65 years	4 Participants n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	10 Participants n=5 Participants
HCV genotype 1a	3 Participants n=5 Participants
HCV genotype 1b	4 Participants n=5 Participants
HCV genotype 4	2 Participants n=5 Participants
HCV genotype mixed	1 Participants n=5 Participants
CKD stage 1	3 Participants n=5 Participants
CKD stage 2	2 Participants n=5 Participants
CKD stage 3	5 Participants n=5 Participants
Baseline HCV RNA	1,573,500 IU/mL n=5 Participants
Prior PEG-IFN/ribavirin treatment	4 Participants n=5 Participants
Hypertension	9 Participants n=5 Participants
Diabetes mellitus	5 Participants n=5 Participants
Coronary artery disease	2 Participants n=5 Participants
Congestive heart failure	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	12 Weeks Treatment With Sofosbuvir/Ledipasvir (400mg/90mg) n=10 Participants Participants received sofosbuvir/Ledipasvir FDC for 12 weeks treatment (10 total dosed on protocol) Proteinuria is assessed at baseline (initiation of treatment) and at 24 weeks after baseline (12 weeks after completion of treatment.
The Percent Change in Proteinuria	-14 percentage change from baseline Interval -42.0 to 52.0

SECONDARY outcome

Timeframe: 24 weeks

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]

Outcome measures

Measure	12 Weeks Treatment With Sofosbuvir/Ledipasvir (400mg/90mg) n=10 Participants Participants received sofosbuvir/Ledipasvir FDC for 12 weeks treatment (10 total dosed on protocol) Proteinuria is assessed at baseline (initiation of treatment) and at 24 weeks after baseline (12 weeks after completion of treatment.
Median Change in eGFR From Baseline to Timepoint Week 24	1 mL/min/1.73m^2 Interval -1.0 to 2.75

SECONDARY outcome

Timeframe: 24 weeks

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.

Outcome measures

Measure	12 Weeks Treatment With Sofosbuvir/Ledipasvir (400mg/90mg) n=10 Participants Participants received sofosbuvir/Ledipasvir FDC for 12 weeks treatment (10 total dosed on protocol) Proteinuria is assessed at baseline (initiation of treatment) and at 24 weeks after baseline (12 weeks after completion of treatment.
Number of Participants With ≥25% Reduction in Proteinuria	3 Participants

SECONDARY outcome

Timeframe: 52 weeks

Population: Because 3 patients had rising proteinuria they are not included in this analysis, which only looks at the mean time to reduction in proteinuria in the 7 patients who had any reductions in proteinuria. This includes the 3 patients who had -25% change in proteinuria and 4 patients who had smaller negative changes (reductions) 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.

Outcome measures

Measure	12 Weeks Treatment With Sofosbuvir/Ledipasvir (400mg/90mg) n=7 Participants Participants received sofosbuvir/Ledipasvir FDC for 12 weeks treatment (10 total dosed on protocol) Proteinuria is assessed at baseline (initiation of treatment) and at 24 weeks after baseline (12 weeks after completion of treatment.
Mean Time in Weeks to Maximum Reduction in Proteinuria	39.4 weeks Standard Deviation 12.7

SECONDARY outcome

Timeframe: 52 weeks

Population: Sofosbuvir/Ledipasvir FDC: 12 weeks treatment with Harvoni (10 total dosed on protocol)

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]

Outcome measures

Measure	12 Weeks Treatment With Sofosbuvir/Ledipasvir (400mg/90mg) n=10 Participants Participants received sofosbuvir/Ledipasvir FDC for 12 weeks treatment (10 total dosed on protocol) Proteinuria is assessed at baseline (initiation of treatment) and at 24 weeks after baseline (12 weeks after completion of treatment.
Median Change in eGFR From Baseline to Timepoint Week 52	-4 mL/min/1.73m^2 Interval -11.25 to 2.0

SECONDARY outcome

Timeframe: 24 weeks

Population: Data were not collected and the outcome cannot be reported. Values for urinary β-2microglobulin were obtained at baseline and not at screening. Thus we are unable to report a "change in urinary β-2microglobulin levels BEFORE therapy with ledipasvir/sofosbuvir" - however, we are able to report the changes after therapy as followup values were done.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 24 weeks

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.

Outcome measures

Measure	12 Weeks Treatment With Sofosbuvir/Ledipasvir (400mg/90mg) n=10 Participants Participants received sofosbuvir/Ledipasvir FDC for 12 weeks treatment (10 total dosed on protocol) Proteinuria is assessed at baseline (initiation of treatment) and at 24 weeks after baseline (12 weeks after completion of treatment.
Change in Urinary β-2microglobulin Levels After Therapy	57 mcg/L Interval -14.0 to 546.0

Adverse Events

12 Weeks Treatment With Sofosbuvir/Ledipasvir (400mg/90mg)

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Measure	12 Weeks Treatment With Sofosbuvir/Ledipasvir (400mg/90mg) n=10 participants at risk Sofosbuvir/Ledipasvir FDC: 12 weeks treatment with Harvoni (10 total dosed on protocol) Patients were followed for one year following treatment initiation
Gastrointestinal disorders intestinal blockage	10.0% 1/10 • Number of events 1 • Data was collected over 52 week study period (which includes 12 weeks of treatment with Harvoni, and 40 weeks of post-treatment follow-up).

Other adverse events

Measure	12 Weeks Treatment With Sofosbuvir/Ledipasvir (400mg/90mg) n=10 participants at risk Sofosbuvir/Ledipasvir FDC: 12 weeks treatment with Harvoni (10 total dosed on protocol) Patients were followed for one year following treatment initiation
General disorders fatigue	30.0% 3/10 • Number of events 4 • Data was collected over 52 week study period (which includes 12 weeks of treatment with Harvoni, and 40 weeks of post-treatment follow-up).
General disorders nausea	20.0% 2/10 • Number of events 2 • Data was collected over 52 week study period (which includes 12 weeks of treatment with Harvoni, and 40 weeks of post-treatment follow-up).
Skin and subcutaneous tissue disorders rash	10.0% 1/10 • Number of events 1 • Data was collected over 52 week study period (which includes 12 weeks of treatment with Harvoni, and 40 weeks of post-treatment follow-up).
General disorders headache	20.0% 2/10 • Number of events 2 • Data was collected over 52 week study period (which includes 12 weeks of treatment with Harvoni, and 40 weeks of post-treatment follow-up).
Gastrointestinal disorders reduced appetite	10.0% 1/10 • Number of events 1 • Data was collected over 52 week study period (which includes 12 weeks of treatment with Harvoni, and 40 weeks of post-treatment follow-up).
Gastrointestinal disorders acid reflux	10.0% 1/10 • Number of events 2 • Data was collected over 52 week study period (which includes 12 weeks of treatment with Harvoni, and 40 weeks of post-treatment follow-up).
Musculoskeletal and connective tissue disorders back/joint pain	10.0% 1/10 • Number of events 1 • Data was collected over 52 week study period (which includes 12 weeks of treatment with Harvoni, and 40 weeks of post-treatment follow-up).
Vascular disorders elevated blood prsesure	10.0% 1/10 • Number of events 1 • Data was collected over 52 week study period (which includes 12 weeks of treatment with Harvoni, and 40 weeks of post-treatment follow-up).
Musculoskeletal and connective tissue disorders mouth pain	10.0% 1/10 • Number of events 1 • Data was collected over 52 week study period (which includes 12 weeks of treatment with Harvoni, and 40 weeks of post-treatment follow-up).
Psychiatric disorders forgetfulness	10.0% 1/10 • Number of events 1 • Data was collected over 52 week study period (which includes 12 weeks of treatment with Harvoni, and 40 weeks of post-treatment follow-up).
Renal and urinary disorders frequent urination	10.0% 1/10 • Number of events 1 • Data was collected over 52 week study period (which includes 12 weeks of treatment with Harvoni, and 40 weeks of post-treatment follow-up).
Renal and urinary disorders elevated creatinine	10.0% 1/10 • Number of events 1 • Data was collected over 52 week study period (which includes 12 weeks of treatment with Harvoni, and 40 weeks of post-treatment follow-up).
Musculoskeletal and connective tissue disorders fall / twisted ankle	10.0% 1/10 • Number of events 1 • Data was collected over 52 week study period (which includes 12 weeks of treatment with Harvoni, and 40 weeks of post-treatment follow-up).

Additional Information

Dr. Meghan Sise

Massachusetts General Hospital

Phone: 617-726-5050

Email: MSise@partners.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place