Pilot Study to Assess Efficacy and Safety of Sofosbuvir/Ledipasvir Fixed-dose Combination in Treatment Experienced Subjects With Hepatitis C Virus (HCV) Genotype 1 - HIV Co-infection

HIV Clinical Trial

Official title:

Pilot Study to Assess Efficacy and Safety of Sofosbuvir/Ledipasvir (GS-5885) Fixed-dose Combination in NS3/4A Protease Inhibitor-experienced Subjects With HCV Genotype 1 Infection and HIV Co-infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02125500
• Other study ID #: ANRS HC31 SOFTRIH
• Status: Completed
• Phase: Phase 2
• First received: April 24, 2014
• Last updated: June 28, 2017
• Start date: August 2014
• Est. completion date: December 2015

Study information

• Verified date: June 2017
• Source: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Aim of the study is to assess the efficacy and safety of 24 weeks of oral Sofosbuvir/Ledipasvir fixed-dose combination (FDC) in subjects with HCV genotype 1 infection and HIV co-infection, who have previously failed a NS3/4A protease inhibitor plus Pegylated interferon /ribavirin regimen or stopped prematurely their treatment for intolerance.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Confirmed HIV infection

• Infection with HCV genotype 1 only, confirmed at screen visit, with a HCV-RNA = 1000 InternationalUnit(IU)/mL at screen visit

• Treatment-experienced subjects with:

• previous virological failure to tritherapy with Peginterferon/Ribavirin and protease inhibitor,

• or premature discontinuation of previous tritherapy with Peginterferon/Ribavirin and protease inhibitor due to intolerance to Peginterferon or protease inhibitor

• Anti-HCV treatment stopped for at least the last 3 months

• Patients on a stable (for more than 1 month) antiretroviral treatment consisting of an emtricitabine/tenofovir or lamivudine/tenofovir standard of care backbone plus efavirenz or raltegravir or rilpivirine or enfuvirtide. Alternative combinations of the above listed medications may be allowed.

• Dendritic cells 4 > 100/mm3 and > 15% at screen visit

• HIV-RNA < 50cp/ml for more than 3 months at screen visit

• Any liver fibrosis grade, with the assessment of the presence or not of cirrhosis at screening, cirrhosis being defined as a METAVIR score of F4 on the liver puncture biopsy and/or with hepatic impulse elastometry = 14,5 kilopascal (kPa):

• Previous liver biopsy exhibiting cirrhosis lesions (METAVIR F4),

• and/or significant liver biopsy (cumulative length = 15mm or = 5 portal spaces), within the past 18 months

• and/or significant and reliable liver stiffness assessment (Fibroscan®) within the past 6 months (at least 10 measures with IQR less than 30% of the median value and a success rate of at least 70%).

• Female patients with child-bearing potential, and their heterosexual partners must use adequate contraception from the date of screening until 90 days after administration of the last dose of study drug. Male participants must agree to consistently and correctly use a condom, while their female partner must use adequate contraception from the date of screening until 90 days after administration of the last dose of study drug

• Body weight =40 kg and =125 kg

• Informed and signed consent for the main study and the Pharmacokinetic (PK ) sub-study (for the participating patients)

• Patients with Health insurance

Non inclusion Criteria:

• Child-Pugh B or C cirrhosis or history of decompensated cirrhosis.

• Co-infection with Hepatitis B virus (HBV) (AgHBs +) with HBV DNA > 1000 UI/ml

• Pregnant or breast-feeding women

• Transplant recipients

• Opportunistic infections (stage C), active or occurred within 6 months prior to baseline

• Evolutive malignancy, including hepatocarcinoma which should be controlled prior to baseline

• Alcohol or drug consumption which may affect the study participation according to the investigator. Patients included in a programme of substitution with methadone or buprenorphine could be enrolled. The opinion of a consultant in addictology is recommended for patients presenting with current drug use or drug use during the previous year.

• Patients with a history of non-adherence, who will be at risk of being unable to respect the study follow-up timetable

• Patients participating in another clinical trial within 30 days prior to inclusion

• Hb < 10 g/dL (female) or < 11g/dL (male)

• Platelets < 50 000/mm3

• Neutrophil count < 750/mm3

• Renal failure defined as creatinin clearance (MDRD) < 60ml/min

• Other antiretroviral drugs than those allowed in the study

• Contra-indications to Sofosbuvir, Ledipasvir

• Contra-indicated treatment likely to interfere with the study drugs as listed in the protocol

Related Conditions & MeSH terms

• Coinfection
• Hepatitis
• Hepatitis C
• HIV
• Viral Hepatitis C

Intervention

Drug:
• Sofosbuvir/Ledipasvir fixed dose
SOF 400 mg/LDV 90 mg FDC tablet administered orally once daily

Locations

Country	Name	City	State
France	Centre de Méthodologie et de Gestion de Rennes	Rennes

Sponsors (1)

Lead Sponsor	Collaborator
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sustained virologic response 12 weeks after discontinuation of therapy (SVR12), i.e. at week 36.		12 weeks post-treatment
Secondary	Adverse clinical and biological events that occur during the treatment and up to 24 weeks after the end of the treatment		up to 24 weeks after the end of the treatment
Secondary	Number and causes of poor adherence and treatment interruptions		at 1,2,3,4,8,12,16, 20, 24 weeks during treatment, 4, 8,14,18,24 weeks after treatment discontinuationeeks after discontinuation of drugs
Secondary	SVR rate 24 weeks (i.e. W48) after the end of treatment and according to the HCV sub-type		Week 48
Secondary	Number of patients with HCV resistance mutations to Sofosbuvir and/or Ledipasvir		from Day(D)0 to Week (W)24
Secondary	HCV viral load		at Day 0, Week 1, 2, 4, 8, 12, 16, 20, week 24, and 4, 8, 12, 18 and 24 weeks after the end of the treatment
Secondary	Plasma HIV RNA levels		at Day 0, Week 4, 8, 12, 16, 20, 24, 36 and Week 48
Secondary	Assess drug-drug interactions between HCV et HIV drugs	Describe pharmacokinetic parameters of HIV drugs at Day 0 and Week 4 Describe pharmacokinetic parameters of Sofosbuvir and Ledipasvir at Week 4	Day 0 and Week 4
Secondary	Patient's reported outcomes evaluation		Day 0, Week 12, Week 24 and Week 36