Clinical trial NCT02243280: 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
Official title: An Open-Label, Multicenter Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Co-Administration of ABT-493 and ABT-530 With and Without Ribavirin in Subjects With Chronic Hepatitis C Virus (HCV) Genotype 1, 4, 5, and 6 Infection (SURVEYOR-I)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2014-09-17
Enrollment: 174
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: This study consisted of two independent parts: Part 1 was conducted first followed by Part 2. Part 1 enrolled participants who received ABT-493 and ABT-530 for 12 weeks; Part 2 enrolled participants who received ABT-493 and ABT-530 for 8 or 12 weeks. Participants who completed or prematurely discontinued the treatment period were followed for 24 weeks to monitor HCV RNA to evaluate efficacy and the emergence and persistence of viral variants.

Eligibility criteria: Inclusion Criteria:

1. Male or female between 18 and 70 years of age, inclusive, at time of screening
2. Screening laboratory result indicating hepatitis C virus (HCV) GT1 (Study Parts 1 and 2) or GT4, GT5, or GT6 (Study Part 2) infection
3. 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)
4. 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)
5. 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

Exclusion Criteria:

1. History of severe, life-threatening or other significant sensitivity to any drug
2. 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
3. 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
4. Positive test result at Screening for hepatitis B surface antigen (HBsAg) or anti-human immunodeficiency virus antibody (HIV Ab)
5. Hepatitis C virus (HCV) genotype performed during screening indicating co-infection with more than one HCV genotype
6. Any cause of liver disease other than chronic HCV infection
7. Participants with plasma HCV RNA load ≤ 10,000 international units (IU)/mL or unquantifiable or undetectable HCV RNA at screening
8. Previous use of an HCV direct-acting antiviral agent (DAA)
9. 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)
10. 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

Primary outcomes:
measure: Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks Post-treatment
timeFrame: 12 weeks after the last actual dose of study drug
Secondary outcomes:
measure: Percentage of Participants With Sustained Virologic Response (SVR) 4 Weeks Post-treatment
timeFrame: 4 weeks after the last actual dose of study drug
measure: Percentage of Participants With On-treatment Virologic Failure
timeFrame: Screening, Day 1, Day 3, treatment weeks 1, 2, 4, 6, 8, 10, and 12 or premature discontinuation from treatment
measure: Percentage of Participants With Post-treatment Relapse
timeFrame: From the end of treatment through 12 weeks after the last dose of study drug
Other outcomes:
Locations:
Study officials:
affiliation: AbbVie
name: Armen Asatryan, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.