A study to assess the safety and efficacy of ledipasvir/sofosbuvir in adults with chronic HCV infection

• Register: EUCTR
• Last refreshed on: 5 September 2016
• Main ID: EUCTR2015-000690-13-EE
• Date of registration: 17/03/2015
• Prospective Registration: Yes
• Primary sponsor: Gilead Sciences, Inc.
• Public title: A study to assess the safety and efficacy of ledipasvir/sofosbuvir in adults with chronic HCV infection
• Scientific title: A Phase 3b, Multicenter, Open-Label Study to Evaluate the Safety and Efficacy of Ledipasvir/Sofosbuvir in Adults with Chronic HCV Infection.
• Date of first enrolment: 17/04/2015
• Target sample size: 155
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-000690-13
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: Placebo: Other: Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Estonia, Russian Federation

Contacts

• Name: Clinical Trials Mailbox
• Affiliation: Gilead Sciences International Ltd

• Name: Clinical Trials Mailbox
• Affiliation: Gilead Sciences International Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
1. Willing and able to provide written informed consent.
2. Male or female, age = 18 years.
4. Confirmed chronic HCV infection documented by medical history or, if available, liver biopsy
5. HCV genotype:
a. Groups 1 and 2: HCV genotype 1 at screening as determined by the Central Laboratory. Any non-definitive results will exclude the subject from study participation.
b. Group 3: HCV genotype 1 or 3; historical genotype results from GS-US-334-0119 is acceptable.
6. Subjects in Groups 1 and 2 may not have cirrhosis at screening. Subjects in Group 3 may have compensated cirrhosis at screening
7. Body mass index (BMI) = 18 kg/m2
8. Screening ECG without clinically significant abnormalities.
9. Subjects must have the following laboratory parameters at screening:
a. ALT = 10 x the upper limit of normal (ULN)
b. AST = 10 x ULN
c. Hemoglobin = 12 g/dL for male, = 11 g/dL for female subjects
d. Platelets = 50,000 cells/mL
e. INR = 1.5 x ULN unless subject has known hemophilia or is stable on an anticoagulant regimen affecting INR
f. Albumin = 3 g/dL
g. Direct bilirubin = 1.5 x ULN
h. HbA1c = 10%
i. Creatinine clearance (CLcr) = 60 mL/min, as calculated by the Cockcroft- Gault equation
Subjects being screened for Group 3 who currently do not fulfill all of the above laboratory
requirements may be enrolled at the request of the Investigator and with the approval of the
Gilead Medical Monitor or Study Director.
10. Subject has not been treated with any investigational drug or device within 30 days of the screening visit.
11. A female subject is eligible to enter the study if it is confirmed that she is:
- Not pregnant or nursing
- Of non-childbearing potential
- Of childbearing potential agreeing to the terms described in the protocol.
12. All male study participants must agree to consistently and correctly use a condom from Baseline until 7 months after the last dose of RBV (or 90 days after their last dose of LDV/SOF if not taking RBV) . If their female partner is of childbearing potential, their female partner must use 1 of the methods of birth control as described in the protocol
13. Subject must be of generally good health as determined by the Investigator.
14. Subject must be able to comply with the dosing instructions for study drug administration and able to complete the study schedule of assessments.
15. For HIV/HCV coinfected subjects
a. If subject is ARV-naïve, CD4 T-cell count must be > 500 cells/mL.
b. Subjects receiving ARV therapy must:
- have completed at least 6 months of any prior HIV ARV therapy and maintained HIV RNA < 50 copies/mL (or < LLOQ if the local laboratory assay’s LLOQ is =50 copies/mL) prior to Screening
- be on a stable protocol-approved ARV regimen for at least 8 weeks, or for at least 6 months for abacavir-containing regimens, prior to Screening and expected to maintain the same ARV regimen for the duration of the study. Subjects on abacavir-containing regimens must also have had a negative test for HLA-B*5701 and not have experienced any hypersensitivity reaction to abacavir.
- have a CD4 T-cell count > 200 cells/mm3 at Screening.
Subjects with an isolated or unconfirmed HIV RNA > 50 copies/mL (or > LLOQ if the local laboratory assay’s LLOQ is = 50 copies/mL) are not excluded.
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 150
F.1.3 Elderly (>=65 years) yes

Exclusion criteria:
1. Groups 1 and 2: Prior exposure to IFN, RBV, or other approved or experimental direct-acting antiviral targeting the HCV. Group 3: Prior exposure to any HCV treatment within the last 12 weeks prior to screening or who have received treatment with an NS5A inhibitor at any time.
Subject did not participate in study GS-US-334-0119 or achieved SVR12 following treatment with SOF+RBV in study GS-US-334-0119.
2. Pregnant or nursing female or male with pregnant female partner.
3. Chronic liver disease of a non-HCV etiology
4. Infection with hepatitis B virus (HBV).
5. Groups 1 and 3: Infection with human immunodeficiency virus (HIV).
6. Group 3: Contraindication to RBV therapy, eg, history of clinically significant hemoglobinopathy.
7. History of malignancy diagnosed or treated within 5 years.
8. Chronic use of systemically administered immunosuppressive agents
9. Clinically-relevant drug or alcohol abuse within 12 months of screening.
10. Excessive alcohol ingestion.
11. History of solid organ transplantation.
12. Current or prior history of clinical hepatic decompensation.
13. History of clinically-significant illness or any other major medical disorder that may interfere with subject treatment, assessment or compliance with the protocol.
14. History of a gastrointestinal disorder (or post-operative condition) that could interfere with the absorption of the study drug.
15. History of significant pulmonary disease, significant cardiac disease or porphyria.
16. History of difficulty with blood collection and/or poor venous access for the purposes of phlebotomy.
17. Use of any prohibited concomitant medications as described in teh protocol.
18. Known hypersensitivity to RBV, the study investigational medicinal product, the metabolites, or formulation excipients, as applicable.
19. For HIV/HCV coinfected subjects:
a. Opportunistic infection within 6 months prior to Screening
b. Active, serious infection (other than HIV-1 or HCV) requiring parenteral antibiotics, antivirals or antifungals within 30 days prior to baseline
c. For subjects receiving ARV therapy, treatment with a regimen other than one of those listed in the protocol.


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

Health Condition(s) or Problem(s) studied

Chronic Hepatitis C Virus Infection
MedDRA version: 18.0 Level: LLT Classification code 10019751 Term: Hepatitis C virus System Organ Class: 100000004848

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

Intervention(s)

Trade Name: Harvoni
Product Name: Ledipasvir/Sofosbuvir fixed dose combination tablets
Product Code: GS-5885/GS-7977
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Sofosbuvir
CAS Number: 1190307-88-0
Current Sponsor code: GS-7977
Other descriptive name: SOFOSBUVIR
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 400-
INN or Proposed INN: Ledipasvir
CAS Number: 1256388-51-8
Current Sponsor code: GS-5885
Other descriptive name: LEDIPASVIR
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 90-

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

Primary Outcome(s)

Main Objective: - To determine the antiviral efficacy of ledipasvir/sofosbuvir (LDV/SOF) +/- ribavirin (RBV) in subjects with chronic HCV infection as measured by the proportion of subjects in each treatment group with sustained viral response 12 weeks after discontinuation of therapy (SVR12)
- To assess the safety and tolerability of LDV/SOF +/- RBV in subjects with chronic HCV infection as measured by review of the accumulated safety data

Secondary Objective: - To determine the proportion subjects in each treatment group who attain SVR at 4 and 24 weeks after discontinuation of therapy (SVR4 and SVR24)
- To evaluate the kinetics of circulating HCV RNA during treatment and after treatment discontinuation
- To evaluate the emergence of viral resistance to SOF and/or LDV, as relevant, during treatment and after treatment discontinuation
- To assess the proportion of HIV/HCV coinfected subjects that maintain HIV-1 RNA <50 copies/mL while on HCV treatment and at Post-Treatment Week 4
- To assess the change from baseline in CD4 T-cell count at the end of treatment and at Post-Treatment Week 4

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

Primary end point(s): The primary efficacy endpoint is SVR12 (HCV RNA < LLOQ 12 weeks after discontinuation of therapy) in the Full Analysis Set (FAS).

Secondary Outcome(s)

Secondary end point(s): Secondary efficacy endpoints include 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 Day 1, and the proportion of subjects with virologic failure.

Timepoint(s) of evaluation of this end point: 4 and 24 weeks after discontinuation of therapy.

Secondary ID(s)

GS-US-337-1463

Source(s) of Monetary Support

Gilead Sciences, Inc.