A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Co-administration of ABT-493 and ABT-530 With and Without Ribavirin in Subjects With HCV Genotype 1, 4, 5, and 6 Infection

NCT02243280 | Completed Phase 2 Results

• 2 other identifiers: M14-8672014-002925-36
• Study Type: interventional
• Target: 174
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this Phase 2, open-label, 2-part, multicenter study was to evaluate the efficacy, safety, and pharmacokinetics of co-administration of ABT-493 and ABT-530 with and without ribavirin (RBV) at different doses in chronic Hepatitis C virus (HCV) Genotype 1 (GT1), Genotype 4 (GT4), Genotype 5 (GT5), and Genotype 6 (GT6) infection with compensated cirrhosis (GT1 only) or without cirrhosis (GT1, GT4, GT5, or GT6). Although RBV was initially planned in the protocol, it was not administered in any of the study arms.

Conditions

Chronic Hepatitis C; Hepatitis C Virus; HCV

Keywords

HCV GT4; Hepatitis C virus; HCV GT1; HCV; Compensated Cirrhosis; HCV GT6; Hepatitis C Genotype 4 (GT 4); Hepatitis C Genotype 1 (GT1); RBV; Cirrhotic; Hepatitis C; Interferon (IFN) Free; IFN free; HCV GT5; Chronic Hepatitis C; Ribavirin; Child Pugh A; Hepatitis C Genotype 5 (GT 5); Hepatitis C Genotype 6 (GT 6); ABT-493; ABT-530; glecaprevir; pibrentasvir

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks Post-treatment

  The percentage of participants with sustained virologic response (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 Outcomes (3)

• Percentage of Participants With Sustained Virologic Response (SVR) 4 Weeks Post-treatment

  4 weeks after the last actual dose of study drug

• Percentage of Participants With On-treatment Virologic Failure

  Screening, Day 1, Day 3, treatment weeks 1, 2, 4, 6, 8, 10, and 12 or premature discontinuation from treatment

• Percentage of Participants With Post-treatment Relapse

  From the end of treatment through 12 weeks after the last dose of study drug

Study Arms (11)

Arm A

EXPERIMENTAL

ABT-493 200 mg once daily (QD) + ABT-530 120 mg QD for 12 weeks in HCV genotype 1-infected participants without cirrhosis

Drug: ABT-493; Drug: ABT-530

Arm B

EXPERIMENTAL

ABT-493 200 mg once daily (QD) + ABT-530 40 mg QD for 12 weeks in HCV genotype 1- infected participants without cirrhosis

Drug: ABT-493; Drug: ABT-530

Arm C

EXPERIMENTAL

ABT-493 200 mg once daily (QD) + ABT-530 120 mg QD for 8 weeks in HCV genotype 1-infected participants without cirrhosis (never opened - Sponsor decision)

Drug: ABT-493; Drug: ABT-530

Arm D

EXPERIMENTAL

ABT-493 200 mg once daily (QD) + ABT-530 40 mg QD for 8 weeks in HCV genotype 1-infected participants without cirrhosis (never opened - Sponsor decision)

Drug: ABT-493; Drug: ABT-530

Arm E

EXPERIMENTAL

ABT-493 200 mg once daily (QD) + ABT-530 120 mg QD + ribavirin (RBV) 800 mg QD for 12 weeks in HCV genotype 1-infected participants with compensated cirrhosis (never opened - Sponsor decision)

Drug: ABT-493; Drug: ABT-530

Arm F

EXPERIMENTAL

ABT-493 200 mg once daily (QD) + ABT-530 120 mg QD for 12 weeks in HCV genotype 1- infected participants with compensated cirrhosis

Drug: ABT-493; Drug: ABT-530

Arm G

EXPERIMENTAL

ABT-493 200 mg once daily (QD) + ABT-530 40 mg QD + ribavirin (RBV) 800 mg QD for 12 weeks in HCV genotype 1-infected participants with compensated cirrhosis (never opened - Sponsor decision)

Drug: ABT-493; Drug: ABT-530

Arm H

EXPERIMENTAL

ABT-493 200 mg once daily (QD) + ABT-530 40 mg QD for 12 weeks in HCV genotype 1-infected participants with compensated cirrhosis (never opened - Sponsor decision)

Drug: ABT-493; Drug: ABT-530

Arm I

EXPERIMENTAL

ABT-493 300 mg once daily (QD) + ABT-530 120 mg QD for 12 weeks in HCV genotype 4-, 5-, and 6-infected participants without cirrhosis

Drug: ABT-493; Drug: ABT-530

Arm J

EXPERIMENTAL

ABT-493 200 mg once daily (QD) + ABT-530 40 mg QD for 12 weeks in HCV genotype 4-, 5-, and 6-infected participants without cirrhosis (never opened - Sponsor decision)

Drug: ABT-493; Drug: ABT-530

Arm K

EXPERIMENTAL

ABT-493 300 mg once daily (QD) + ABT-530 120 mg QD for 8 weeks in HCV genotype 1- infected participants without cirrhosis

Drug: ABT-493; Drug: ABT-530

Interventions

ABT-493 DRUG

Tablet

Also known as: glecaprevir

Arm A; Arm B; Arm C; Arm D; Arm E; Arm F; Arm G; Arm H; Arm I; Arm J; Arm K

ABT-530 DRUG

Tablet

Also known as: pibrentasvir

Arm A; Arm B; Arm C; Arm D; Arm E; Arm F; Arm G; Arm H; Arm I; Arm J; Arm K

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female between 18 and 70 years of age, inclusive, at time of screening
• Screening laboratory result indicating hepatitis C virus (HCV) GT1 (Study Parts 1 and 2) or GT4, GT5, or GT6 (Study Part 2) infection
• Chronic HCV infection defined as one of the following:
• Positive for anti-HCV antibody (Ab) or HCV RNA at least 6 months before screening, and positive for HCV RNA and anti-HCV Ab at the time of screening or
• Positive for anti-HCV Ab and HCV RNA at the time of screening with a liver biopsy consistent with chronic HCV infection (or a liver biopsy performed prior to enrollment with evidence of chronic HCV infection)
• Participant had to meet one of the following criteria:
• Treatment-naïve: participant had never received treatment for HCV infection
• Treatment-experienced: pegylated-interferon alpha-2a or alpha-2b and ribavirin (PR)-null responder (for Study Part 1) or PR-experienced (on-treatment failure or prior relapse) (for Study Part 2)
• Documented absence of cirrhosis (in Study Part 1 and in corresponding arms of Study Part 2), or compensated cirrhosis (in corresponding arms of Study Part 2, GT1 only), per local standard

You may not qualify if:

• History of severe, life-threatening or other significant sensitivity to any drug
• Female who is pregnant, planning to become pregnant during the study or breastfeeding; or male whose partner is 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)
• Hepatitis C virus (HCV) genotype performed during screening indicating co-infection with more than one HCV genotype
• Any cause of liver disease other than chronic HCV infection
• Participants with plasma HCV RNA load ≤ 10,000 international units (IU)/mL or unquantifiable or undetectable HCV RNA at screening
• Previous use of an HCV direct-acting antiviral agent (DAA)
• Consideration by the investigator, for any reason, that the participant was an unsuitable candidate to receive ABT-493, ABT-530, or RBV (RBV for cirrhotic subjects only)
• For participants in Study Part 2 who were enrolling with compensated cirrhosis: past clinical evidence of Child-Pugh B or C Classification (score of \> 6) or clinical history of liver decompensation, including ascites (noted on physical exam), bleeding varices, use of beta-blockers for portal hypertension or ascites, or hepatic encephalopathy

Sponsors & Collaborators

• AbbVie: lead

Related Publications (6)

• Gane E, Poordad F, Wang S, Asatryan A, Kwo PY, Lalezari J, Wyles DL, Hassanein T, Aguilar H, Maliakkal B, Liu R, Lin CW, Ng TI, Kort J, Mensa FJ. High Efficacy of ABT-493 and ABT-530 Treatment in Patients With HCV Genotype 1 or 3 Infection and Compensated Cirrhosis. Gastroenterology. 2016 Oct;151(4):651-659.e1. doi: 10.1053/j.gastro.2016.07.020. Epub 2016 Jul 25.

  PMID: 27456384 BACKGROUND

• Back D, Belperio P, Bondin M, Negro F, Talal AH, Park C, Zhang Z, Pinsky B, Crown E, Mensa FJ, Marra F. Efficacy and safety of glecaprevir/pibrentasvir in patients with chronic HCV infection and psychiatric disorders: An integrated analysis. J Viral Hepat. 2019 Aug;26(8):951-960. doi: 10.1111/jvh.13110. Epub 2019 May 20.

  PMID: 30977945 DERIVED

• Gane E, Poordad F, Zadeikis N, Valdes J, Lin CW, Liu W, Asatryan A, Wang S, Stedman C, Greenbloom S, Nguyen T, Elkhashab M, Worns MA, Tran A, Mulkay JP, Setze C, Yu Y, Pilot-Matias T, Porcalla A, Mensa FJ. Safety and Pharmacokinetics of Glecaprevir/Pibrentasvir in Adults With Chronic Genotype 1-6 Hepatitis C Virus Infections and Compensated Liver Disease. Clin Infect Dis. 2019 Oct 30;69(10):1657-1664. doi: 10.1093/cid/ciz022.

  PMID: 30923816 DERIVED

• Naganuma A, Chayama K, Notsumata K, Gane E, Foster GR, Wyles D, Kwo P, Crown E, Bhagat A, Mensa FJ, Otani T, Larsen L, Burroughs M, Kumada H. Integrated analysis of 8-week glecaprevir/pibrentasvir in Japanese and overseas patients without cirrhosis and with hepatitis C virus genotype 1 or 2 infection. J Gastroenterol. 2019 Aug;54(8):752-761. doi: 10.1007/s00535-019-01569-7. Epub 2019 Mar 13.

  PMID: 30868245 DERIVED

• Flamm S, Reddy KR, Zadeikis N, Hassanein T, Bacon BR, Maieron A, Zeuzem S, Bourliere M, Calleja JL, Kosloski MP, Oberoi RK, Lin CW, Yu Y, Lovell S, Semizarov D, Mensa FJ. Efficacy and Pharmacokinetics of Glecaprevir and Pibrentasvir With Concurrent Use of Acid-Reducing Agents in Patients With Chronic HCV Infection. Clin Gastroenterol Hepatol. 2019 Feb;17(3):527-535.e6. doi: 10.1016/j.cgh.2018.07.003. Epub 2018 Sep 10.

  PMID: 30012435 DERIVED

• Kwo PY, Poordad F, Asatryan A, Wang S, Wyles DL, Hassanein T, Felizarta F, Sulkowski MS, Gane E, Maliakkal B, Overcash JS, Gordon SC, Muir AJ, Aguilar H, Agarwal K, Dore GJ, Lin CW, Liu R, Lovell SS, Ng TI, Kort J, Mensa FJ. Glecaprevir and pibrentasvir yield high response rates in patients with HCV genotype 1-6 without cirrhosis. J Hepatol. 2017 Aug;67(2):263-271. doi: 10.1016/j.jhep.2017.03.039. Epub 2017 Apr 13.

  PMID: 28412293 DERIVED

MeSH Terms

Conditions

Hepatitis C, Chronic; Hepatitis C

Interventions

glecaprevir; pibrentasvir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Global Medical Services
• Organization: AbbVie

800-633-9110

Study Officials

• Armen Asatryan, MD

  AbbVie

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2014
• First Posted: September 17, 2014
• Study Start: August 1, 2014
• Primary Completion: February 1, 2016
• Study Completion: February 1, 2016
• Last Updated: July 13, 2021
• Results First Posted: April 6, 2017

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share