A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Co-Administration of ABT-493 and ABT-530 With and Without RBV in Subjects With Chronic Hepatitis C Virus (HCV) Genotypes 2, 3, 4, 5 or 6 Infection

Study Overview
=================
Brief Summary
-----------------
The purpose of this phase 2/3, open-label, multipart, multicenter study was to evaluate the efficacy, and safety of co-administration of ABT-493 and ABT-530 with and without ribavirin (RBV) in chronic HCV genotype 2 (GT2-), genotype 3 (GT3-), genotype 4 (GT4), genotype 5 (GT5-), or genotype 6 (GT6-) infected participants with or without cirrhosis.

Detailed Description
-----------------
The study consisted of four independent parts with treatment and post-treatment periods of enrollment. Parts 1 and 2 were the supportive/ exploratory parts (phase 2) of the study and part 3 and 4 were the confirmatory/ registrational parts (phase 3) of the study. In parts 1 and 2 of the study, ABT-493 and ABT-530 were co-administered as separate tablets. However, in parts 3 and 4 of the study, the ABT-493/ABT-530 co-formulated tablets were administered.

Official Title
-----------------
A Randomized, Open-Label, Multicenter Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Co-Administration of ABT-493 and ABT-530 With and Without RBV in Subjects With Chronic Hepatitis C Virus (HCV) Genotypes 2, 3, 4, 5 or 6 Infection (SURVEYOR-II)

Conditions
-----------------
Chronic Hepatitis C, Hepatitis C Virus

Intervention / Treatment
-----------------
* Drug: ABT-493
* Drug: ABT-530
* Drug: ribavirin (RBV)
* Drug: ABT-493/ABT-530


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Screening laboratory result indicating HCV Genotype 2, 3, 4, 5, or 6 infection. Chronic HCV infection. Participant had to be either HCV treatment-naïve or treatment-experienced. Participant had to be documented as non-cirrhotic or as having compensated cirrhosis (GT3 only). Exclusion Criteria: History of severe, life-threatening or other significant sensitivity to any drug. Female who was pregnant, planning to become pregnant during the study, or breastfeeding; or male whose partner was pregnant or planning to become pregnant during the study. Recent (within 6 months prior to study drug administration) history of drug or alcohol abuse that could preclude adherence to the protocol in the opinion of the investigator. Positive test result at Screening for hepatitis B surface antigen (HBsAg) or anti-human immunodeficiency virus antibody (HIV Ab). HCV genotype performed during screening indicating co-infection with more than one HCV genotype.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>ABT-493 (300 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 12 weeks in HCV genotype 2 (GT2) -infected treatment naïve and treatment experienced participants without cirrhosis. | Drug: ABT-493<br>* Tablet<br>* Other names: glecaprevir;Drug: ABT-530<br>* Tablet<br>* Other names: pibrentasvir;|
| Experimental: Arm B<br>ABT-493 (200 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 12 weeks in HCV GT2 -infected treatment naïve and treatment experienced participants without cirrhosis. | Drug: ABT-493<br>* Tablet<br>* Other names: glecaprevir;Drug: ABT-530<br>* Tablet<br>* Other names: pibrentasvir;|
| Experimental: Arm C<br>ABT-493 (200 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD and weight-based ribavirin (RBV) divided twice daily (BID) for 12 weeks in HCV GT2 -infected treatment naïve and treatment experienced participants without cirrhosis. | Drug: ABT-493<br>* Tablet<br>* Other names: glecaprevir;Drug: ABT-530<br>* Tablet<br>* Other names: pibrentasvir;Drug: ribavirin (RBV)<br>* Tablet<br>|
| Experimental: Arm D<br>ABT-493 (300 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 12 weeks in HCV genotype 3 (GT3) -infected treatment naïve and treatment experienced participants without cirrhosis. | Drug: ABT-493<br>* Tablet<br>* Other names: glecaprevir;Drug: ABT-530<br>* Tablet<br>* Other names: pibrentasvir;|
| Experimental: Arm E<br>ABT-493 (200 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 12 weeks in HCV GT3 -infected treatment naïve and treatment experienced participants without cirrhosis. | Drug: ABT-493<br>* Tablet<br>* Other names: glecaprevir;Drug: ABT-530<br>* Tablet<br>* Other names: pibrentasvir;|
| Experimental: Arm F<br>ABT-493 (200 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD and weight-based ribavirin (RBV) divided BID for 12 weeks in HCV GT3 -infected treatment naïve and treatment experienced participants without cirrhosis. | Drug: ABT-493<br>* Tablet<br>* Other names: glecaprevir;Drug: ABT-530<br>* Tablet<br>* Other names: pibrentasvir;Drug: ribavirin (RBV)<br>* Tablet<br>|
| Experimental: Arm G<br>ABT-493 (200 mg) once daily (QD) co-administered with ABT-530 (40 mg) QD for 12 weeks in HCV GT3 -infected treatment naïve and treatment experienced participants without cirrhosis. | Drug: ABT-493<br>* Tablet<br>* Other names: glecaprevir;Drug: ABT-530<br>* Tablet<br>* Other names: pibrentasvir;|
| Experimental: Arm H<br>ABT-493 (200 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 8 weeks in HCV GT2 -infected treatment naïve and treatment experienced participants without cirrhosis. | Drug: ABT-493<br>* Tablet<br>* Other names: glecaprevir;Drug: ABT-530<br>* Tablet<br>* Other names: pibrentasvir;|
| Experimental: Arm I<br>ABT-493 (200 mg) once daily (QD) co-administered with ABT-530 (40 mg) QD for 8 weeks in HCV GT2 -infected treatment naïve and treatment experienced participants without cirrhosis. | Drug: ABT-493<br>* Tablet<br>* Other names: glecaprevir;Drug: ABT-530<br>* Tablet<br>* Other names: pibrentasvir;|
| Experimental: Arm J<br>ABT-493 (300 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 8 weeks in HCV GT2 -infected treatment naïve and treatment experienced participants without cirrhosis. | Drug: ABT-493<br>* Tablet<br>* Other names: glecaprevir;Drug: ABT-530<br>* Tablet<br>* Other names: pibrentasvir;|
| Experimental: Arm K<br>ABT-493 (200 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 8 weeks in HCV GT3 -infected treatment naïve and treatment experienced participants without cirrhosis. | Drug: ABT-493<br>* Tablet<br>* Other names: glecaprevir;Drug: ABT-530<br>* Tablet<br>* Other names: pibrentasvir;|
| Experimental: Arm L<br>ABT-493 (300 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 8 weeks in HCV GT3 -infected treatment naïve and for 12 weeks in HCV GT3 -infected treatment experienced participants without cirrhosis. | Drug: ABT-493<br>* Tablet<br>* Other names: glecaprevir;Drug: ABT-530<br>* Tablet<br>* Other names: pibrentasvir;|
| Experimental: Arm M<br>ABT-493 (200 mg) once daily (QD) co-administered with ABT-530 (80 mg) QD for 12 weeks in HCV GT3 -infected treatment naïve participants with compensated cirrhosis. | Drug: ABT-493<br>* Tablet<br>* Other names: glecaprevir;Drug: ABT-530<br>* Tablet<br>* Other names: pibrentasvir;|
| Experimental: Arm N<br>ABT-493 (200 mg) once daily (QD) co-administered with ABT-530 (80 mg) QD and ribavirin (RBV) (800 mg) QD for 12 weeks in HCV GT3 -infected treatment naïve participants with compensated cirrhosis. | Drug: ABT-493<br>* Tablet<br>* Other names: glecaprevir;Drug: ABT-530<br>* Tablet<br>* Other names: pibrentasvir;Drug: ribavirin (RBV)<br>* Tablet<br>|
| Experimental: Arm O<br>ABT-493 (300 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 12 weeks in HCV GT3 -infected treatment naïve participants with compensated cirrhosis and for 16 weeks in HCV GT3 -infected treatment-experienced participants with compensated cirrhosis. | Drug: ABT-493<br>* Tablet<br>* Other names: glecaprevir;Drug: ABT-530<br>* Tablet<br>* Other names: pibrentasvir;|
| Experimental: Arm P<br>ABT-493 (300 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD and RBV (800 mg) QD for 12 weeks in HCV GT3-infected treatment naïve and treatment-experienced participants with compensated cirrhosis. | Drug: ABT-493<br>* Tablet<br>* Other names: glecaprevir;Drug: ABT-530<br>* Tablet<br>* Other names: pibrentasvir;Drug: ribavirin (RBV)<br>* Tablet<br>|
| Experimental: Arm Q1<br>ABT-493/ ABT-530 (300 mg/ 120mg ) once daily (QD) for 12 weeks in HCV GT3 -infected treatment naïve participants with cirrhosis. | Drug: ABT-493/ABT-530<br>* Tablet; ABT-493 co-formulated ABT-530<br>* Other names: MAVYRET;|
| Experimental: Arm Q2<br>ABT-493/ ABT-530 (300 mg/ 120mg ) once daily (QD) for 12 weeks in HCV GT3 -infected treatment experienced participants without cirrhosis. | Drug: ABT-493/ABT-530<br>* Tablet; ABT-493 co-formulated ABT-530<br>* Other names: MAVYRET;|
| Experimental: Arm R1<br>ABT-493/ ABT-530 (300 mg/ 120 mg) QD for 16 weeks in HCV GT3 -infected treatment experienced participants without cirrhosis. | Drug: ABT-493/ABT-530<br>* Tablet; ABT-493 co-formulated ABT-530<br>* Other names: MAVYRET;|
| Experimental: Arm R2<br>ABT-493/ ABT-530 (300 mg/ 120 mg) QD for 16 weeks in HCV GT3 -infected treatment experienced participants with cirrhosis. | Drug: ABT-493/ABT-530<br>* Tablet; ABT-493 co-formulated ABT-530<br>* Other names: MAVYRET;|
| Experimental: Arm S1<br>ABT-493/ ABT-530 (300 mg/ 120 mg) QD for 8 weeks in HCV GT2 infected treatment naïve and treatment experienced participants without cirrhosis. | Drug: ABT-493/ABT-530<br>* Tablet; ABT-493 co-formulated ABT-530<br>* Other names: MAVYRET;|
| Experimental: Arm S2<br>ABT-493/ ABT-530 (300 mg/ 120 mg) QD for 8 weeks in HCV GT4-6 infected treatment naïve and treatment experienced participants without cirrhosis. | Drug: ABT-493/ABT-530<br>* Tablet; ABT-493 co-formulated ABT-530<br>* Other names: MAVYRET;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification [<LLOQ]) 12 weeks after the last dose of study drug. | 12 weeks after the last actual dose of study drug | 
| Percentage of Genotype 2 (GT2) Direct-acting Antiviral Agents (DAA)-Naive Participants (in Part 4, Arm S1) With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) as Compared to Historical Control | SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification [<LLOQ]) 12 weeks after the last dose of study drug. | 12 weeks after the last actual dose of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virologic Response 4 Weeks Post-treatment (SVR4) | SVR4 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification [<LLOQ]) 4 weeks after the last dose of study drug. | 4 weeks after the last actual dose of study drug | 
| Percentage of Participants With On-treatment Virologic Failure | On-treatment virologic failure was defined as confirmed HCV RNA ≥ LLOQ after HCV RNA < LLOQ during treatment; confirmed increase of > 1 log(subscript)10(subscript) IU/mL above the lowest value post-baseline in HCV RNA during treatment; or HCV RNA ≥ LLOQ at end of treatment with at least 6 weeks of treatment. | Up to end of treatment (treatment week 8, 12 or 16 depending on arm) or premature discontinuation from treatment | 
| Percentage of Participants With Post-treatment Relapse | Post-treatment relapse was defined as confirmed HCV RNA ≥ LLOQ between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment with HCV RNA levels < LLOQ at the end of treatment, excluding reinfection. | From the end of treatment through 12 weeks after the last dose of study drug | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hepatitis C Virus (HCV), Hepatitis C, Chronic Hepatitis C, interferon free, Hepatitis C Genotype 2, Hepatitis C Genotype 3, Hepatitis C Genotype 4, Hepatitis C Genotype 5, Hepatitis C Genotype 6