Brief Summary
The primary objective of this study is to evaluate the efficacy, safety, and tolerability of ledipasvir/sofosbuvir (LDV/SOF) fixed dose combination (FDC) for 12 weeks with or without ribavirin (RBV) in participants without cirrhosis, and LDV/SOF FDC for 12 weeks with RBV or LDV/SOF FDC for 24 weeks without RBV in participants with cirrhosis.
Brief Title
Efficacy and Safety of Ledipasvir/Sofosbuvir, With or Without Ribavirin, in HCV Infected Participants Who Have Failed Prior Treatment With Sofosbuvir-based Therapies
Categories
Completion Date
Completion Date Type
Actual
Conditions
Hepatitis C Virus Infection
Eligibility Criteria
Key Inclusion Criteria:
* HCV RNA \> 15 IU/mL at screening
* HCV genotype 1 or 4
* Chronic HCV infection (≥ 6 months)
* Prior virologic failure after treatment with SOF in combination with simeprevir (SMV) ± RBV or with RBV ± pegylated interferon (PEG)
* Cirrhotic and non-cirrhotic as determined by standard methods
* Male and female individuals of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
Key Exclusion Criteria:
* Prior exposure to approved or experimental non-structural protein (NS5A) inhibitors
* Prior exposure to nucleos(t)ide polymerase inhibitors, other than SOF
* Pregnant or nursing female or male with pregnant female partner
* Coinfection with HIV or hepatitis B virus
* Current or prior history of clinical hepatic decompensation
* Hepatocellular carcinoma or other malignancy (with exception of certain resolved skin cancers)
* Chronic use of systemic immunosuppressive agents
* History of clinically significant illness or any other medical disorder that may interfere with individual's treatment, assessment or compliance with the protocol
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
* HCV RNA \> 15 IU/mL at screening
* HCV genotype 1 or 4
* Chronic HCV infection (≥ 6 months)
* Prior virologic failure after treatment with SOF in combination with simeprevir (SMV) ± RBV or with RBV ± pegylated interferon (PEG)
* Cirrhotic and non-cirrhotic as determined by standard methods
* Male and female individuals of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
Key Exclusion Criteria:
* Prior exposure to approved or experimental non-structural protein (NS5A) inhibitors
* Prior exposure to nucleos(t)ide polymerase inhibitors, other than SOF
* Pregnant or nursing female or male with pregnant female partner
* Coinfection with HIV or hepatitis B virus
* Current or prior history of clinical hepatic decompensation
* Hepatocellular carcinoma or other malignancy (with exception of certain resolved skin cancers)
* Chronic use of systemic immunosuppressive agents
* History of clinically significant illness or any other medical disorder that may interfere with individual's treatment, assessment or compliance with the protocol
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Inclusion Criteria
Inclusion Criteria:
* HCV RNA \> 15 IU/mL at screening
* HCV genotype 1 or 4
* Chronic HCV infection (≥ 6 months)
* Prior virologic failure after treatment with SOF in combination with simeprevir (SMV) ± RBV or with RBV ± pegylated interferon (PEG)
* Cirrhotic and non-cirrhotic as determined by standard methods
* Male and female individuals of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
Inclusion/
* HCV RNA \> 15 IU/mL at screening
* HCV genotype 1 or 4
* Chronic HCV infection (≥ 6 months)
* Prior virologic failure after treatment with SOF in combination with simeprevir (SMV) ± RBV or with RBV ± pegylated interferon (PEG)
* Cirrhotic and non-cirrhotic as determined by standard methods
* Male and female individuals of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
Inclusion/
Gender
All
Gender Based
false
Keywords
Hepatitis C Virus (HCV)
Ledipasvir/Sofosbuvir
Ribavirin
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT02600351
Org Class
Industry
Org Full Name
Gilead Sciences
Org Study Id
GS-US-337-1746
Overall Status
Terminated
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 3b, Multicenter, Open-Label Study to Investigate the Efficacy and Safety of Ledipasvir/Sofosbuvir, With or Without Ribavirin, in HCV Infected Subjects Who Have Failed Prior Treatment With Sofosbuvir-based Therapies
Primary Outcomes
Outcome Description
SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, \< 15 IU/mL) at 12 weeks after stopping study treatment.
Outcome Measure
Percentage of Participants With Sustained Virologic Response 12 Weeks After Cessation of Therapy (SVR12)
Outcome Time Frame
Posttreatment Week 12
Outcome Measure
Percentage of Participants Who Discontinued From Study Treatment for an Adverse Event
Outcome Time Frame
Up to 24 weeks
Secondary Outcomes
Outcome Description
SVR4 and SVR24 were defined as HCV RNA \< LLOQ at 4 and 24 weeks following the last dose of study drug, respectively.
Outcome Time Frame
Posttreatment Weeks 4 and 24
Outcome Measure
Percentage of Participants With HCV RNA < the Lower Limit of Quantitation (LLOQ) at 4 and 24 Weeks Posttreatment
Outcome Description
Viral breakthrough was defined as HCV RNA ≥ LLOQ after having previously had HCV RNA \< LLOQ while receiving treatment.
Outcome Time Frame
Up to 24 weeks
Outcome Measure
Percentage of Participants With Viral Breakthrough
Outcome Description
Viral relapse was defined as confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA \<LLOQ at last on-treatment visit.
Outcome Time Frame
Up to Posttreatment Week 24
Outcome Measure
Percentage of Participants With Viral Relapse
Outcome Description
The full-length NS3, NS5A, and NS5B coding regions were deep sequenced at pretreatment (baseline) for all participants included in the Full Analysis Set, and at posttreatment for all participants who relapsed.
Outcome Time Frame
Up to Posttreatment Week 24
Outcome Measure
Number of Participants With Emerging Resistance
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Samuel Sigal
Investigator Email
ssigal@montefiore.org
Investigator Phone
718-920-6240
Categories Mesh Debug
Hepatitis --- HEPATITIS C
Blood Disorders --- BLOOD-BORNE INFECTIONS
HIV/AIDS --- BLOOD-BORNE INFECTIONS
Infectious Disease --- BLOOD-BORNE INFECTIONS
Hepatitis --- COMMUNICABLE DISEASES
HIV/AIDS --- COMMUNICABLE DISEASES
Infectious Disease --- COMMUNICABLE DISEASES
COVID-19 --- INFECTIONS
Infectious Disease --- INFECTIONS
Hepatitis --- HEPATITIS, VIRAL, HUMAN
COVID-19 --- VIRUS DISEASES
Hepatitis --- VIRUS DISEASES
Infectious Disease --- VIRUS DISEASES
COVID-19 --- RNA VIRUS INFECTIONS
Infectious Disease --- RNA VIRUS INFECTIONS
Hepatitis --- HEPATITIS
Digestive System --- LIVER DISEASES
Liver --- LIVER DISEASES
Gastrointestinal (GI) Cancers --- DIGESTIVE SYSTEM DISEASES
Digestive System --- DIGESTIVE SYSTEM DISEASES
Liver --- DIGESTIVE SYSTEM DISEASES
MeSH Terms
HEPATITIS C
BLOOD-BORNE INFECTIONS
COMMUNICABLE DISEASES
INFECTIONS
HEPATITIS, VIRAL, HUMAN
VIRUS DISEASES
FLAVIVIRIDAE INFECTIONS
RNA VIRUS INFECTIONS
HEPATITIS
LIVER DISEASES
DIGESTIVE SYSTEM DISEASES
LEDIPASVIR, SOFOSBUVIR DRUG COMBINATION