Trial Outcomes & Findings for Safety and Efficacy of Ledipasvir/Sofosbuvir (LDV/SOF) Fixed Dose Combination (FDC) for 12 or 24 Weeks in Kidney Transplant Recipients With Chronic HCV Infection (NCT NCT02251717)
NCT ID: NCT02251717
Last Updated: 2018-11-19
Results Overview
SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
114 participants
Primary outcome timeframe
Posttreatment Week 12
Results posted on
2018-11-19
Participant Flow
Participants were enrolled at study sites in Europe. The first participant was screened on 14 October 2014. The last study visit occurred on 16 June 2016.
130 participants were screened.
Participant milestones
| Measure |
LDV/SOF 12 Weeks
Ledipasvir/sofosbuvir (Harvoni®; LDV/SOF) (90/400 mg) for 12 weeks in participants with chronic genotype 1 or 4 HCV infection who have had a kidney transplant
|
LDV/SOF 24 Weeks
LDV/SOF (90/400 mg) for 24 weeks in participants with chronic genotype 1 or 4 HCV infection who have had a kidney transplant
|
|---|---|---|
|
Overall Study
STARTED
|
57
|
57
|
|
Overall Study
COMPLETED
|
56
|
56
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
Reasons for withdrawal
| Measure |
LDV/SOF 12 Weeks
Ledipasvir/sofosbuvir (Harvoni®; LDV/SOF) (90/400 mg) for 12 weeks in participants with chronic genotype 1 or 4 HCV infection who have had a kidney transplant
|
LDV/SOF 24 Weeks
LDV/SOF (90/400 mg) for 24 weeks in participants with chronic genotype 1 or 4 HCV infection who have had a kidney transplant
|
|---|---|---|
|
Overall Study
Adverse Event
|
0
|
1
|
|
Overall Study
Withdrew Consent
|
1
|
0
|
Baseline Characteristics
Safety and Efficacy of Ledipasvir/Sofosbuvir (LDV/SOF) Fixed Dose Combination (FDC) for 12 or 24 Weeks in Kidney Transplant Recipients With Chronic HCV Infection
Baseline characteristics by cohort
| Measure |
LDV/SOF 12 Weeks
n=57 Participants
LDV/SOF (90/400 mg) for 12 weeks in participants with chronic genotype 1 or 4 HCV infection who have had a kidney transplant
|
LDV/SOF 24 Weeks
n=57 Participants
LDV/SOF (90/400 mg) for 24 weeks in participants with chronic genotype 1 or 4 HCV infection who have had a kidney transplant
|
Total
n=114 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
54 years
STANDARD_DEVIATION 8.3 • n=99 Participants
|
53 years
STANDARD_DEVIATION 10.0 • n=107 Participants
|
53 years
STANDARD_DEVIATION 9.2 • n=206 Participants
|
|
Sex: Female, Male
Female
|
24 Participants
n=99 Participants
|
24 Participants
n=107 Participants
|
48 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
33 Participants
n=99 Participants
|
33 Participants
n=107 Participants
|
66 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
5 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
56 Participants
n=99 Participants
|
53 Participants
n=107 Participants
|
109 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
2 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
White
|
54 Participants
n=99 Participants
|
53 Participants
n=107 Participants
|
107 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Other
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Region of Enrollment
Austria
|
9 participants
n=99 Participants
|
15 participants
n=107 Participants
|
24 participants
n=206 Participants
|
|
Region of Enrollment
Italy
|
32 participants
n=99 Participants
|
17 participants
n=107 Participants
|
49 participants
n=206 Participants
|
|
Region of Enrollment
France
|
15 participants
n=99 Participants
|
21 participants
n=107 Participants
|
36 participants
n=206 Participants
|
|
Region of Enrollment
Germany
|
1 participants
n=99 Participants
|
4 participants
n=107 Participants
|
5 participants
n=206 Participants
|
|
HCV genotype
Genotype 1
|
51 Participants
n=99 Participants
|
53 Participants
n=107 Participants
|
104 Participants
n=206 Participants
|
|
HCV genotype
Genotype 4
|
6 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
10 Participants
n=206 Participants
|
|
Cirrhosis Status
No
|
49 Participants
n=99 Participants
|
48 Participants
n=107 Participants
|
97 Participants
n=206 Participants
|
|
Cirrhosis Status
Yes
|
8 Participants
n=99 Participants
|
9 Participants
n=107 Participants
|
17 Participants
n=206 Participants
|
|
IL28b Status
CC
|
14 Participants
n=99 Participants
|
18 Participants
n=107 Participants
|
32 Participants
n=206 Participants
|
|
IL28b Status
CT
|
34 Participants
n=99 Participants
|
34 Participants
n=107 Participants
|
68 Participants
n=206 Participants
|
|
IL28b Status
TT
|
9 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
14 Participants
n=206 Participants
|
|
Years From Most Recent Kidney Transplant
|
12.1 years
STANDARD_DEVIATION 9.51 • n=99 Participants
|
14.4 years
STANDARD_DEVIATION 9.66 • n=107 Participants
|
13.2 years
STANDARD_DEVIATION 9.61 • n=206 Participants
|
|
HCV RNA
|
6.3 log10 IU/mL
STANDARD_DEVIATION 0.63 • n=99 Participants
|
6.2 log10 IU/mL
STANDARD_DEVIATION 0.53 • n=107 Participants
|
6.3 log10 IU/mL
STANDARD_DEVIATION 0.58 • n=206 Participants
|
|
HCV RNA Category
< 800,000 IU/mL
|
11 Participants
n=99 Participants
|
16 Participants
n=107 Participants
|
27 Participants
n=206 Participants
|
|
HCV RNA Category
≥ 800,000 IU/mL
|
46 Participants
n=99 Participants
|
41 Participants
n=107 Participants
|
87 Participants
n=206 Participants
|
|
Prior HCV Treatment Status
Treatment-Naive
|
40 Participants
n=99 Participants
|
39 Participants
n=107 Participants
|
79 Participants
n=206 Participants
|
|
Prior HCV Treatment Status
Treatment-Experienced
|
17 Participants
n=99 Participants
|
18 Participants
n=107 Participants
|
35 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Posttreatment Week 12Population: Full Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug
SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment.
Outcome measures
| Measure |
LDV/SOF 12 Weeks
n=57 Participants
LDV/SOF (90/400 mg) for 12 weeks in participants with chronic genotype 1 or 4 HCV infection who have had a kidney transplant
|
LDV/SOF 24 Weeks
n=57 Participants
LDV/SOF (90/400 mg) for 24 weeks in participants with chronic genotype 1 or 4 HCV infection who have had a kidney transplant
|
|---|---|---|
|
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)
|
100.0 percentage of participants
Interval 93.7 to 100.0
|
100.0 percentage of participants
Interval 93.7 to 100.0
|
PRIMARY outcome
Timeframe: Up to 24 weeksPopulation: Safety Analysis Set: participants who received at least 1 dose of study drug
Outcome measures
| Measure |
LDV/SOF 12 Weeks
n=57 Participants
LDV/SOF (90/400 mg) for 12 weeks in participants with chronic genotype 1 or 4 HCV infection who have had a kidney transplant
|
LDV/SOF 24 Weeks
n=57 Participants
LDV/SOF (90/400 mg) for 24 weeks in participants with chronic genotype 1 or 4 HCV infection who have had a kidney transplant
|
|---|---|---|
|
Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event
|
1.8 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: Posttreatment Weeks 4 and 24Population: Full Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug
SVR4 and SVR24 were defined as HCV RNA \< LLOQ at 4 and 24 weeks after stopping study treatment, respectively.
Outcome measures
| Measure |
LDV/SOF 12 Weeks
n=57 Participants
LDV/SOF (90/400 mg) for 12 weeks in participants with chronic genotype 1 or 4 HCV infection who have had a kidney transplant
|
LDV/SOF 24 Weeks
n=57 Participants
LDV/SOF (90/400 mg) for 24 weeks in participants with chronic genotype 1 or 4 HCV infection who have had a kidney transplant
|
|---|---|---|
|
Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)
SVR4
|
100.0 percentage of participants
Interval 93.7 to 100.0
|
100.0 percentage of participants
Interval 93.7 to 100.0
|
|
Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)
SVR24
|
100.0 percentage of participants
Interval 93.7 to 100.0
|
100.0 percentage of participants
Interval 93.7 to 100.0
|
SECONDARY outcome
Timeframe: Up to Posttreatment Week 24Population: Full Analysis Set: participants who were randomized into the study and received at least 1 dose of study drug
Virologic failure was defined as: * On-treatment virologic failure: * Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA \< LLOQ while on treatment), or * Rebound (confirmed \> 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or * Non-response (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment) * Virologic relapse: * Confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA \< LLOQ at last on-treatment visit.
Outcome measures
| Measure |
LDV/SOF 12 Weeks
n=57 Participants
LDV/SOF (90/400 mg) for 12 weeks in participants with chronic genotype 1 or 4 HCV infection who have had a kidney transplant
|
LDV/SOF 24 Weeks
n=57 Participants
LDV/SOF (90/400 mg) for 24 weeks in participants with chronic genotype 1 or 4 HCV infection who have had a kidney transplant
|
|---|---|---|
|
Percentage of Participants With Virologic Failure
|
0 percentage of participants
|
0 percentage of participants
|
Adverse Events
LDV/SOF 12 Weeks
Serious events: 5 serious events
Other events: 23 other events
Deaths: 0 deaths
LDV/SOF 24 Weeks
Serious events: 8 serious events
Other events: 36 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
LDV/SOF 12 Weeks
n=57 participants at risk
LDV/SOF (90/400 mg) for 12 weeks in participants with chronic genotype 1 or 4 HCV infection who have had a kidney transplant
|
LDV/SOF 24 Weeks
n=57 participants at risk
LDV/SOF (90/400 mg) for 24 weeks in participants with chronic genotype 1 or 4 HCV infection who have had a kidney transplant
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhoea haemorrhagic
|
0.00%
0/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
1.8%
1/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
|
Infections and infestations
Erysipelas
|
1.8%
1/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
0.00%
0/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
|
Infections and infestations
Gastroenteritis
|
1.8%
1/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
0.00%
0/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
1.8%
1/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
|
Injury, poisoning and procedural complications
Incisional hernia
|
0.00%
0/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
1.8%
1/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
|
Injury, poisoning and procedural complications
Shunt thrombosis
|
0.00%
0/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
1.8%
1/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
|
Investigations
Blood creatinine increased
|
0.00%
0/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
1.8%
1/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.00%
0/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
1.8%
1/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Papillary thyroid cancer
|
0.00%
0/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
1.8%
1/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
|
Nervous system disorders
Syncope
|
1.8%
1/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
0.00%
0/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
|
Psychiatric disorders
Suicide attempt
|
1.8%
1/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
0.00%
0/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
|
Renal and urinary disorders
Acute kidney injury
|
1.8%
1/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
0.00%
0/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
1.8%
1/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
|
Surgical and medical procedures
Arteriovenous shunt operation
|
0.00%
0/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
1.8%
1/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
Other adverse events
| Measure |
LDV/SOF 12 Weeks
n=57 participants at risk
LDV/SOF (90/400 mg) for 12 weeks in participants with chronic genotype 1 or 4 HCV infection who have had a kidney transplant
|
LDV/SOF 24 Weeks
n=57 participants at risk
LDV/SOF (90/400 mg) for 24 weeks in participants with chronic genotype 1 or 4 HCV infection who have had a kidney transplant
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
1.8%
1/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
5.3%
3/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
7.0%
4/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
|
Gastrointestinal disorders
Diarrhoea
|
5.3%
3/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
8.8%
5/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
|
Gastrointestinal disorders
Nausea
|
5.3%
3/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
5.3%
3/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
|
Gastrointestinal disorders
Vomiting
|
5.3%
3/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
1.8%
1/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
|
General disorders
Asthenia
|
14.0%
8/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
14.0%
8/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
|
General disorders
Fatigue
|
7.0%
4/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
12.3%
7/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
|
General disorders
Oedema peripheral
|
0.00%
0/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
5.3%
3/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
|
Infections and infestations
Bronchitis
|
0.00%
0/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
5.3%
3/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
8.8%
5/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
|
Infections and infestations
Urinary tract infection
|
7.0%
4/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
7.0%
4/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
3.5%
2/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
8.8%
5/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
7.0%
4/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
0.00%
0/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
|
Nervous system disorders
Headache
|
15.8%
9/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
22.8%
13/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
|
Nervous system disorders
Somnolence
|
1.8%
1/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
5.3%
3/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
5.3%
3/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.8%
1/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
7.0%
4/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
|
Vascular disorders
Haematoma
|
0.00%
0/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
5.3%
3/57 • Up to 24 weeks plus 30 days
Safety Analysis Set: participants who received at least 1 dose of study drug
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: * The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or * The study has been completed at all study sites for at least 2 years
- Publication restrictions are in place
Restriction type: OTHER