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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02010255




Registration number
NCT02010255
Ethics application status
Date submitted
9/12/2013
Date registered
12/12/2013
Date last updated
19/11/2018

Titles & IDs
Public title
Ledipasvir/Sofosbuvir Fixed-Dose Combination Plus Ribavirin in Participants With Chronic HCV With Advanced Liver Disease or Post-Liver Transplant
Scientific title
A Phase 2, Multicenter, Open-Label Study to Investigate the Safety and Efficacy of Sofosbuvir/Ledipasvir Fixed-Dose Combination + Ribavirin Administered in Subjects Infected With Chronic HCV Who Have Advanced Liver Disease or Are Post-Liver Transplant
Secondary ID [1] 0 0
2013-002802-30
Secondary ID [2] 0 0
GS-US-337-0124
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic HCV Infection 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Cancer 0 0 0 0
Liver

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - LDV/SOF
Treatment: Drugs - RBV

Experimental: Cohort A, Group 1 (12 wk): CPT Class B (7-9) - LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability \[weight-based maximum: \< 75 kg = 1000 mg, = 75 kg = 1200 mg\]) for 12 weeks in participants with CPT Class B (CPT score 7-9)

Experimental: Cohort A, Group 1 (24 wk): CPT Class B (7-9) - LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability \[weight-based maximum: \< 75 kg = 1000 mg, = 75 kg = 1200 mg\]) for 24 weeks in participants with CPT Class B (CPT score 7-9)

Experimental: Cohort A, Group 2 (12 wk): CPT Class C (10-12) - LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability \[weight-based maximum: \< 75 kg = 1000 mg, = 75 kg = 1200 mg\]) for 12 weeks in participants with CPT Class C (CPT score 10-12)

Experimental: Cohort A, Group 2 (24 wk): CPT Class C (10-12) - LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability \[weight-based maximum: \< 75 kg = 1000 mg, = 75 kg = 1200 mg\]) for 24 weeks in participants with CPT Class C (CPT score 10-12)

Experimental: Cohort B, Group 3 (12 wk): F0-F3 Fibrosis - LDV/SOF (90/400 mg) plus RBV (weight-based: \< 75 kg = 1000 mg, = 75 kg = 1200 mg) for 12 weeks in participants with Fibrosis Stage F0-F3

Experimental: Cohort B, Group 3 (24 wk): F0-F3 Fibrosis - LDV/SOF (90/400 mg) plus RBV (weight-based: \< 75 kg = 1000 mg, = 75 kg = 1200 mg) for 24 weeks in participants with Fibrosis Stage F0-F3

Experimental: Cohort B, Group 4 (12 wk): CPT Class A (5-6) - LDV/SOF (90/400 mg) plus RBV (weight-based: \< 75 kg = 1000 mg, = 75 kg = 1200 mg) for 12 weeks in participants with CPT Class A (CPT score 5-6)

Experimental: Cohort B, Group 4 (24 wk): CPT Class A (5-6) - LDV/SOF (90/400 mg) plus RBV (weight-based: \< 75 kg = 1000 mg, = 75 kg = 1200 mg) for 24 weeks in participants with CPT Class A (CPT score 5-6)

Experimental: Cohort B, Group 5 (12 wk): CPT Class B (7-9) - LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability \[weight-based maximum: \< 75 kg = 1000 mg, = 75 kg = 1200 mg\]) for 12 weeks in participants with CPT Class B (CPT score 7-9)

Experimental: Cohort B, Group 5 (24 wk): CPT Class B (7-9) - LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability \[weight-based maximum: \< 75 kg = 1000 mg, = 75 kg = 1200 mg\]) for 24 weeks in participants with CPT Class B (CPT score 7-9)

Experimental: Cohort B, Group 6 (12 wk): CPT Class C (10-12) - LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability \[weight-based maximum: \< 75 kg = 1000 mg, = 75 kg = 1200 mg\]) for 12 weeks in participants with CPT Class C (CPT score 10-12)

Experimental: Cohort B, Group 6 (24 wk): CPT Class C (10-12) - LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability \[weight-based maximum: \< 75 kg = 1000 mg, = 75 kg = 1200 mg\]) for 24 weeks in participants with CPT Class C (CPT score 10-12)

Experimental: Cohort B, Group 7 (12 wk): FCH - LDV/SOF (90/400 mg) plus RBV (weight-based: \< 75 kg = 1000 mg, = 75 kg = 1200 mg) for 12 weeks in participants with FCH

Experimental: Cohort B, Group 7 (24 wk): FCH - LDV/SOF (90/400 mg) plus RBV (weight-based: \< 75 kg = 1000 mg, = 75 kg = 1200 mg) for 24 weeks in participants with FCH


Treatment: Drugs: LDV/SOF
LDV/SOF FDC tablet administered orally once daily

Treatment: Drugs: RBV
RBV tablets administered orally in a divided daily dose
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)
Timepoint [1] 0 0
Posttreatment Week 12
Primary outcome [2] 0 0
Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event
Timepoint [2] 0 0
Up to 24 weeks
Secondary outcome [1] 0 0
Percentage of Participants With SVR 2 Weeks After Discontinuation of Therapy (SVR2)
Timepoint [1] 0 0
Posttreatment Week 2
Secondary outcome [2] 0 0
Percentage of Participants With SVR 4 Weeks After Discontinuation of Therapy (SVR4)
Timepoint [2] 0 0
Posttreatment Week 4
Secondary outcome [3] 0 0
Percentage of Participants With SVR 8 Weeks After Discontinuation of Therapy (SVR8)
Timepoint [3] 0 0
Posttreatment Week 8
Secondary outcome [4] 0 0
Percentage of Participants With SVR 24 Weeks After Discontinuation of Therapy (SVR24)
Timepoint [4] 0 0
Posttreatment Week 24
Secondary outcome [5] 0 0
Percentage of Participants With Virologic Failure
Timepoint [5] 0 0
Up to Posttreatment Week 24
Secondary outcome [6] 0 0
Percentage of Participants With Posttransplant Virologic Response (pTVR) at Posttransplant Week 12
Timepoint [6] 0 0
Posttreatment Week 12
Secondary outcome [7] 0 0
Percentage of Participants With HCV RNA < LLOQ at Week 1
Timepoint [7] 0 0
Week 1
Secondary outcome [8] 0 0
Percentage of Participants With HCV RNA < LLOQ at Week 2
Timepoint [8] 0 0
Week 2
Secondary outcome [9] 0 0
Percentage of Participants With HCV RNA < LLOQ at Week 4
Timepoint [9] 0 0
Week 4
Secondary outcome [10] 0 0
Percentage of Participants With HCV RNA < LLOQ at Week 6
Timepoint [10] 0 0
Week 6
Secondary outcome [11] 0 0
Percentage of Participants With HCV RNA < LLOQ at Week 8
Timepoint [11] 0 0
Week 8
Secondary outcome [12] 0 0
Percentage of Participants With HCV RNA < LLOQ at Week 12
Timepoint [12] 0 0
Week 12
Secondary outcome [13] 0 0
Percentage of Participants With HCV RNA < LLOQ at Week 16
Timepoint [13] 0 0
Week 16
Secondary outcome [14] 0 0
Percentage of Participants With HCV RNA < LLOQ at Week 20
Timepoint [14] 0 0
Week 20
Secondary outcome [15] 0 0
Percentage of Participants With HCV RNA < LLOQ at Week 24
Timepoint [15] 0 0
Week 24
Secondary outcome [16] 0 0
HCV RNA Levels and Change From Baseline at Week 1
Timepoint [16] 0 0
Baseline; Week 1
Secondary outcome [17] 0 0
HCV RNA Levels and Change From Baseline at Week 2
Timepoint [17] 0 0
Baseline; Week 2
Secondary outcome [18] 0 0
HCV RNA Levels and Change From Baseline at Week 4
Timepoint [18] 0 0
Baseline; Week 4
Secondary outcome [19] 0 0
HCV RNA Levels and Change From Baseline at Week 6
Timepoint [19] 0 0
Baseline; Week 6
Secondary outcome [20] 0 0
HCV RNA Levels and Change From Baseline at Week 8
Timepoint [20] 0 0
Baseline; Week 8
Secondary outcome [21] 0 0
HCV RNA Levels and Change From Baseline at Week 12
Timepoint [21] 0 0
Baseline; Week 12
Secondary outcome [22] 0 0
Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 4 in MELD Score
Timepoint [22] 0 0
Baseline to Posttreatment Week 4
Secondary outcome [23] 0 0
Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 4 in CPT Score
Timepoint [23] 0 0
Baseline to Posttreatment Week 4

Eligibility
Key inclusion criteria
* Able to provide written informed consent
* Chronic genotype 1 and/or 4 HCV infection
* Normal ECG
* Negative serum pregnancy test for female subjects
* Male subjects and female subjects of childbearing potential must agree to use contraception
* Able to comply with the dosing instructions for study drug and able to complete the study schedule of assessments, including all required post treatment visits
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Serious or active medical or psychiatric illness
* HIV or hepatitis B viral (HBV) infection
* Stomach disorder that could interfere with the absorption of the study drug
* Treated with an anti-HCV medication in the last 30 days
* Any prior exposure to an HCV nonstructural protein (NS)5a-specific inhibitor
* Use of human granulocyte-macrophage colony-stimulating factor (GM-CSF), epoetin alfa or other therapeutic hematopoietic agents within 2 weeks of screening
* History of clinically significant medical condition associated with other chronic liver disease
* Active spontaneous bacterial peritonitis at screening
* Females who are breastfeeding
* Infection requiring systemic antibiotics
* Participated in a clinical study with an investigational drug or biologic within the last 30 days
* Active or history (last 6 months) of drug or alcohol abuse
* History of organ transplant other than liver, kidney, or corneal.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/01/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/08/2015
Sample size
Target
Accrual to date
Final
334
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital, University of Sydney - Camperdown
Recruitment hospital [2] 0 0
Austin Repatriation Hospital (Melbourne) // Victorian Transplant Centre - Heidelberg
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 0 0
Austria
State/province [1] 0 0
Innsbruck
Country [2] 0 0
Austria
State/province [2] 0 0
Wien
Country [3] 0 0
Belgium
State/province [3] 0 0
Brussels
Country [4] 0 0
Belgium
State/province [4] 0 0
Gent
Country [5] 0 0
Canada
State/province [5] 0 0
Alberta
Country [6] 0 0
Canada
State/province [6] 0 0
British Columbia
Country [7] 0 0
Canada
State/province [7] 0 0
Ontario
Country [8] 0 0
Canada
State/province [8] 0 0
Quebec
Country [9] 0 0
France
State/province [9] 0 0
Clichy Cedex
Country [10] 0 0
France
State/province [10] 0 0
Créteil
Country [11] 0 0
France
State/province [11] 0 0
Montpellier
Country [12] 0 0
France
State/province [12] 0 0
Villejuif Cedex
Country [13] 0 0
Germany
State/province [13] 0 0
Aachen
Country [14] 0 0
Germany
State/province [14] 0 0
Essen
Country [15] 0 0
Germany
State/province [15] 0 0
Frankfurt
Country [16] 0 0
Germany
State/province [16] 0 0
Hannover
Country [17] 0 0
Italy
State/province [17] 0 0
Milano
Country [18] 0 0
Italy
State/province [18] 0 0
Torino
Country [19] 0 0
Netherlands
State/province [19] 0 0
Leiden
Country [20] 0 0
Netherlands
State/province [20] 0 0
Rotterdam
Country [21] 0 0
New Zealand
State/province [21] 0 0
Auckland
Country [22] 0 0
Spain
State/province [22] 0 0
Barcelona
Country [23] 0 0
Spain
State/province [23] 0 0
Madrid
Country [24] 0 0
Spain
State/province [24] 0 0
Valencia
Country [25] 0 0
Switzerland
State/province [25] 0 0
Bern
Country [26] 0 0
Switzerland
State/province [26] 0 0
Zurich
Country [27] 0 0
United Kingdom
State/province [27] 0 0
Birmingham
Country [28] 0 0
United Kingdom
State/province [28] 0 0
Edinburgh
Country [29] 0 0
United Kingdom
State/province [29] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Gilead Sciences
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study will evaluate ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) plus ribavirin (RBV) in participants with advanced liver disease or posttransplant and chronic genotype 1 or 4 hepatitis C virus (HCV) infection.

* Cohort A: decompensated cirrhosis (advanced liver disease), no prior liver transplant;
* Cohort B: post-liver transplant, with or without cirrhosis;
* Group assignment within cohorts is based on severity of liver impairment at screening (Child-Pugh-Turcotte (CPT) score for participants with cirrhosis; fibrosis; or presence of disease for fibrosing cholestatic hepatitis (FCH) groups)
* Randomization is 1:1 within groups to 12 or 24 weeks of LDV/SOF+RBV treatment.
Trial website
https://clinicaltrials.gov/study/NCT02010255
Trial related presentations / publications
Manns M, Samuel D, Gane EJ, Mutimer D, McCaughan G, Buti M, Prieto M, Calleja JL, Peck-Radosavljevic M, Mullhaupt B, Agarwal K, Angus P, Yoshida EM, Colombo M, Rizzetto M, Dvory-Sobol H, Denning J, Arterburn S, Pang PS, Brainard D, McHutchison JG, Dufour JF, Van Vlierberghe H, van Hoek B, Forns X; SOLAR-2 investigators. Ledipasvir and sofosbuvir plus ribavirin in patients with genotype 1 or 4 hepatitis C virus infection and advanced liver disease: a multicentre, open-label, randomised, phase 2 trial. Lancet Infect Dis. 2016 Jun;16(6):685-697. doi: 10.1016/S1473-3099(16)00052-9. Epub 2016 Feb 18. Erratum In: Lancet Infect Dis. 2016 Jun;16(6):636. doi: 10.1016/S1473-3099(16)30085-8.
Public notes

Contacts
Principal investigator
Name 0 0
Shampa De-Oertel, PhD
Address 0 0
Gilead Sciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02010255