An international study to assess the safety and efficacy of a combination of new investigational drugs in patients with chronic hepatitis C virus infection who have previously failed treatment in a clinical study run by Gilead.

• Register: EUCTR
• Last refreshed on: 8 February 2016
• Main ID: EUCTR2014-001245-24-ES
• Date of registration: 04/07/2014
• Prospective Registration: Yes
• Primary sponsor: Gilead Sciences, Inc.
• Public title: An international study to assess the safety and efficacy of a combination of new investigational drugs in patients with chronic hepatitis C virus infection who have previously failed treatment in a clinical study run by Gilead.
• Scientific title: An open-Label, multicenter study to evaluate the efficacy and safety of sofosbuvir/ledipasvir fixed-dose combination ± ribavirin for 12 or 24 weeks in chronic genotype 1 HCV infected subjects who participated in a prior gilead-sponsored HCV treatment study
• Date of first enrolment: 01/10/2014
• Target sample size: 110
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-001245-24
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 3

Countries of recruitment

Australia, New Zealand, Spain, United States

Contacts

• Name: Medical Monitor
• Affiliation: Gilead Sciences Inc.

• Name: Medical Monitor
• Affiliation: Gilead Sciences Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects must meet all of the following inclusion criteria to be eligible for participation in this
study.
1) Willing and able to provide written informed consent
2) HCV genotype (GT) 1 (Historical result from prior Gilead study is acceptable)
3) HCV RNA >LLOQ at Screening
4) Participated in one of the following Gilead-sponsored studies:
- Group 1
o P7977-0221
o P7977-0422 (PROTON)
o P-7977-0724 (ATOMIC)
o GS-US-334-0110 (NEUTRINO)
o P2938-0721(QUANTUM)
- Group 2
o GS-US-337-0118 (LONESTAR)
o GS-US-337-0133 (LONESTAR 3)
o GS-US-337-0102 (ION-1)
o GS-US-337-0108 (ION-3)
o GS-US-337-0109 (ION-2)
- Group 3
o GS-US-334-0125
- Subjects that participated in other Gilead-sponsored HCV treatment studies will require pre-approval by Gilead Medical Monitor or Study Director. Subjects must not have withdrawn consent or have been terminated early due to investigator
discretion from the prior study.
5) Liver imaging within 6 months of Baseline/Day 1 to exclude hepatocellular carcinoma (HCC) is required in patients with cirrhosis. Cirrhosis is defined as any of the following:
o Prior diagnosis of cirrhosis
o FibroTest score of > 0.75 AND an AST:platelet ratio index (APRI) of > 2 during Screening
6) Screening ECG without clinically significant abnormalities
7) Subjects must have the following laboratory parameters at screening
- Group 1 & Group 2 only:
o ALT o AST o Direct bilirubin o Platelets >/= 50,000/µL
o HbA1c o Creatinine clearance (CLcr) >/= 60 mL /min, as calculated by the Cockcroft-Gault equation
o Hemoglobin >/= 11 g/dL for female subjects; >/= 12 g/dL for male subjects.
o Albumin >/= 3g/dL
o INR - Group 3:
o Hemoglobin (Hb) > 10 g/dL
o Platelets >/= 30,000/ mm3
o Creatinine /= 40 mL /min, as calculated by the Cockcroft-Gault equation
o Sodium >125 mmol/L
o Total bilirubin < 10 mg/dL
Subjects who met laboratory eligibility criteria in their parent protocol, but do not fulfill all of the above requirements may be enrolled at the request of the Investigator and with the approval of the Medical Monitor or Study Director
8) Females of childbearing potential (as defined in Appendix 4) must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day -1 prior to randomization.
9) Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception as described in Appendix 4.
10) Subject must be of generally good health, with the exception of chronic HCV infection, as determined by the Investigator.
11) Subject must be able to comply with the dosing instructions for study drug administration and able to complete the study schedule of assessments.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 95
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15

Exclusion criteria:
Subjects who meet any of the following exclusion criteria are not be enrolled in this study.
1) Current or prior history of any of the following:
a) Clinically-significant illness (other than HCV) or any other major medical disorder that may interfere with subject treatment, assessment or compliance with the protocol.
b) Gastrointestinal disorder or post-operative condition that could interfere with the absorption of the study drug.
2) Pregnant or nursing female or male with pregnant female partner.
3) Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV).
4) In the judgment of the investigator any clinically-relevant drug or alcohol abuse within 12 months of screening that may interfere with subject treatment, assessment or compliance with the protocol.
5) Contraindications to RBV therapy, including significant history of clinically significant hemoglobinopathy (e.g., sickle cell disease, thalassemia).
6) Use of any prohibited concomitant medications as described in the Protocol Section 5.4
7) Known hypersensitivity to RBV, sofosbuvir, ledipasvir, the metabolites or formulation excipients.
8) On-treatment virologic failure in prior Gilead-sponsored HCV treatment studies

Group 1 and Group 2 Additional Exclusion Criteria
9) Subjects currently under evaluation for a potentially clinically-significant illness (other than HCV) [Groups 1& 2 only]
10) Current or prior history of Clinical hepatic decompensation (i.e., ascites, encephalopathy or variceal hemorrhage) [Groups 1& 2 only].

Group 3 Additional Exclusion Criteria
11) Untreated, active variceal bleeding within 6 months of screening [Group 3 only]
12) Patients with a Child-Pugh-Turcotte score > 12 [Group 3 only]
13) History of organ transplant. Patients with prior liver or kidney transplant may be eligible with Medical Monitor approval. [Group 3 only]
14) Any current signs or symptoms of severe hepatic encephalopathy, that in the opinion of the Investigator may affect the ability of the subject to provide initial and continuing informed consent to participate. [Group 3 only]
15) History of hepatorenal, or hepatopulmonary syndrome. [Group 3 only]
16) Active spontaneous bacterial peritonitis at screening. [Group 3 only]


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Chronic Genotype 1 Hepatitis C Virus Infection
MedDRA version: 17.0 Level: LLT Classification code 10019751 Term: Hepatitis C virus System Organ Class: 100000004848

Therapeutic area: Diseases [C] - Virus Diseases [C02]

Intervention(s)

Product Name: Sofosbuvir/Ledipasvir FDC
Product Code: GS-7977/GS-5885 FDC
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Sofosbuvir
CAS Number: 1190307-88-0
Current Sponsor code: GS-7977
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 400-
INN or Proposed INN: GS-5885
Current Sponsor code: GS-5885
Other descriptive name: GS-5885
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 90-

Trade Name: Ribasphere Tablets
Product Name: Ribasphere
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Ribavirin
CAS Number: 36791-04-5
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Primary Outcome(s)

Main Objective: The primary objectives of this study are:
- To determine the efficacy of sofosbuvir/ledipasvir fixed-dose combination (SOF/LDV FDC) ± ribavirin (RBV) as measured by the proportion of subjects with sustained viral response at 12 weeks after discontinuation of therapy (SVR12).
- To evaluate the safety and tolerability of SOF/LDV FDC ± RBV as assessed by review of the accumulated safety data.

Timepoint(s) of evaluation of this end point: 12 weeks after discontinuation of therapy

Secondary Objective: The secondary objectives of this study are:
- To determine the proportion of subjects who attain SVR at 4 and 24 weeks after discontinuation of therapy (SVR4 and SVR24)
- To evaluate the kinetics of plasma HCV RNA during and after treatment discontinuation
- To evaluate the emergence of viral resistance to SOF and LDV during and after treatment discontinuation

Primary end point(s): The primary efficacy endpoint is SVR12 (HCV RNA

Secondary Outcome(s)

Secondary end point(s): The proportion of subjects with: HCV RNA < LLOQ at 4 and 24 weeks after discontinuation of therapy (SVR4 and SVR24)

The proportion of subjects with HCV RNA < LLOQ on treatment

HCV RNA change from Baseline/Day 1

The proportion of subjects with virologic failure

Timepoint(s) of evaluation of this end point: Secondary endpoints will be assessed at On-Treatment visits at the end of Weeks 1, 4, 8, 12 and Post-Treatment visit Weeks 4, 12 (if applicable), and 24 (if applicable).

For subjects in Groups 2 and 3, additional On-Treatment visits will occur at the end of
Weeks 16, 20, and 24.

Secondary ID(s)

GS-US-337-1118

Source(s) of Monetary Support

Gilead Sciences Inc.