A Study to Evaluate the Efficacy and Safety of ABT-493/ABT-530 in Subjects With Genotype 1 Infection

• ClinicalTrials.gov Identifier: NCT02604017
• Recruitment Status: Completed
• First Posted: November 13, 2015
• Results First Posted: September 14, 2017
• Last Update Posted: July 13, 2021
• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

Tracking Information

• First Submitted Date: November 11, 2015
• First Posted Date: November 13, 2015
• Results First Submitted Date: August 17, 2017
• Results First Posted Date: September 14, 2017
• Last Update Posted Date: July 13, 2021
• Study Start Date: October 2015
• Actual Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 17, 2017)

• Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) in Mono-infected Hepatitis C Virus Genotype 1 (HCV GT1), Direct-acting Antiviral Agent (DAA) Naïve Participants in the 12-Week Treatment Arm [ Time Frame: 12 weeks after the last actual dose of study drug ]
  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. The primary efficacy endpoint was noninferiority of the percentage of participants who achieved SVR12 in the 12-week treatment group compared with the historical control rate for HCV GT1 subjects who are treatment-naïve or treated with pegylated-interferon alfa-2a or alfa-2b and ribavirin (pegIFN/RBV).
• Percentage of Participants With SVR12: Noninferiority of 8-Week Arm to 12-Week Arm in Mono-infected HCV GT1, DAA-Naïve Participants, Excluding Those Who Discontinued/Experienced Virologic Failure by Week 8 or Had No HCV RNA Value at Week 12 or Later [ Time Frame: 12 weeks after last actual dose of study drug ]
  SVR12 was defined as plasma HCV RNA level <LLOQ 12 weeks after the last dose of study drug. The primary efficacy endpoint was noninferiority of the percentage of mono-infected HCV GT1, DAA-naïve participants (excluding those who discontinued/experienced virologic failure by Week 8 or had no HCV RNA value at Week 12 or later) who achieved SVR12 in the 8-week treatment arm compared with the 12-week treatment arm.
• Percentage of Participants With SVR12: Noninferiority of 8-Week Treatment Arm to 12-Week Treatment Arm in Mono-infected HCV GT1, DAA-Naïve Participants [ Time Frame: 12 weeks after the last actual dose of study drug ]
  SVR12 was defined as plasma HCV RNA level <LLOQ 12 weeks after the last dose of study drug. The primary efficacy endpoint was noninferiority of the percentage of mono-infected HCV GT1, DAA-naïve participants who achieved SVR12 in the 8-week treatment arm compared with the 12-week treatment arm.

Original Primary Outcome Measures (submitted: November 11, 2015)

• Percentage of participants achieving a 12-week sustained virologic response (SVR12) Post-treatment [ Time Frame: 12 weeks after last dose of study drug ]
  HCV RNA level less than the lower limit of quantification.
• Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment in the 8-week Arm compared to the 12-week Arm in the per protocol (PP) population. [ Time Frame: 12 weeks after last dose of study drug ]
  HCV RNA level less than the lower limit of quantification.
• Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment in the 8-week Arm compared to the 12-week Arm in the intent-to-treat (ITT) population. [ Time Frame: 12 weeks after last dose of study drug ]
  HCV RNA level less than the lower limit of quantification.

Current Secondary Outcome Measures (submitted: August 17, 2017)

• Percentage of Participants With SVR12 in Mono-infected HCV GT1 Participants [ Time Frame: 12 weeks after last actual dose of study drug ]
  SVR12 was defined as plasma HCV RNA level <LLOQ 12 weeks after the last dose of study drug.
• Percentage of Participants With SVR12 [ Time Frame: 12 weeks after last actual dose of study drug ]
  SVR12 was defined as plasma HCV RNA level <LLOQ 12 weeks after the last dose of study drug.
• Percentage of Participants With SVR12 in Co-infected HCV GT1/Human Immunodeficiency Virus Type 1 (HIV-1) Participants [ Time Frame: 12 weeks after last actual dose of study drug ]
  SVR12 was defined as plasma HCV RNA level <LLOQ 12 weeks after the last dose of study drug.
• Percentage of Participants With SVR12 in HCV GT1-infected, Prior Sofosbuvir (SOF) Treatment-Experienced Participants [ Time Frame: 12 weeks after last actual dose of study drug ]
  SVR12 was defined as plasma HCV RNA level <LLOQ 12 weeks after the last dose of study drug.
• Percentage of Participants With On-treatment Virologic Failure [ Time Frame: Treatment Weeks 1, 2, 4, 8 (end of treatment for 8-week treatment arm), and 12 (end of treatment for 12-week treatment arm) or premature discontinuation from treatment ]
  On-treatment virologic failure was defined as confirmed increase of >1 log(subscript)10(subscript) IU/mL above the lowest value post-baseline HCV RNA during treatment; confirmed HCV RNA ≥100 IU/mL after HCV RNA <LLOQ during treatment, or HCV RNA ≥LLOQ at end of treatment with at least 6 weeks of treatment.
• Percentage of Participants With On-treatment Virologic Failure in Mono-infected HCV GT1, DAA-Naïve Participants [ Time Frame: Treatment Weeks 1, 2, 4, 8 (end of treatment for 8-week treatment arm), and 12 (end of treatment for 12-week treatment arm) or premature discontinuation from treatment ]
  On-treatment virologic failure was defined as confirmed increase of >1 log(subscript)10(subscript) IU/mL above the lowest value post-baseline HCV RNA during treatment; confirmed HCV RNA ≥100 IU/mL after HCV RNA <LLOQ during treatment, or HCV RNA ≥LLOQ at end of treatment with at least 6 weeks of treatment.
• Percentage of Participants With Post-treatment Relapse [ Time Frame: From the end of treatment through 12 weeks after the last dose of study drug ]
  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.
• Percentage of Participants With Post-treatment Relapse in Mono-infected HCV GT1, DAA-Naïve Participants [ Time Frame: From the end of treatment through 12 weeks after the last dose of study drug ]
  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.

Original Secondary Outcome Measures (submitted: November 11, 2015)

• Percentage of participants with on-treatment virologic failure [ Time Frame: Up to 8 or 12 weeks while on treatment ]
  The percentage of participants with confirmed 1 log10 IU/mL increase from nadir in HCV RNA at any time point during treatment or; with confirmed, quantifiable HCV RNA among subjects with previous unquantifiable HCV RNA during treatment; or failure to suppress during treatment with at least 6 weeks of treatment.
• Percentage of participants with Post-Treatment relapse [ Time Frame: Up to 12 weeks after the last dose of study drug ]
  Percentage of participants with confirmed quantifiable HCV RNA after completion of treatment among participants with unquantifiable HCV RNA at the end of treatment.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate the Efficacy and Safety of ABT-493/ABT-530 in Subjects With Genotype 1 Infection
• Official Title: A Randomized, Open-Label, Multicenter Study to Evaluate the Efficacy and Safety of ABT-493/ABT-530 in Adults With Chronic Hepatitis C Virus Genotype 1 Infection (ENDURANCE-1)
• Brief Summary: This study seeks to evaluate the efficacy and safety of ABT-493/ABT-530 in participants with Genotype 1 hepatitis C virus infection without cirrhosis
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Chronic Hepatitis C
• Hepatitis C Virus
• HCV

Intervention

Drug: ABT-493/ABT-530

Tablet; ABT-493 coformulated with ABT-530

Other Names:

• ABT-493 also known as glecaprevir
• ABT-530 also known as pibrentasvir
• MAVYRET

Study Arms

• Experimental: ABT-493/ABT-530 for 12 weeks
  ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks.
  Intervention: Drug: ABT-493/ABT-530
• Experimental: ABT-493/ABT-530 for 8 weeks
  ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 8 weeks.
  Intervention: Drug: ABT-493/ABT-530

Publications *

• Zeuzem S, Foster GR, Wang S, Asatryan A, Gane E, Feld JJ, Asselah T, Bourlière M, Ruane PJ, Wedemeyer H, Pol S, Flisiak R, Poordad F, Chuang WL, Stedman CA, Flamm S, Kwo P, Dore GJ, Sepulveda-Arzola G, Roberts SK, Soto-Malave R, Kaita K, Puoti M, Vierling J, Tam E, Vargas HE, Bruck R, Fuster F, Paik SW, Felizarta F, Kort J, Fu B, Liu R, Ng TI, Pilot-Matias T, Lin CW, Trinh R, Mensa FJ. Glecaprevir-Pibrentasvir for 8 or 12 Weeks in HCV Genotype 1 or 3 Infection. N Engl J Med. 2018 Jan 25;378(4):354-369. doi: 10.1056/NEJMoa1702417.
• Brown A, Welzel TM, Conway B, Negro F, Bräu N, Grebely J, Puoti M, Aghemo A, Kleine H, Pugatch D, Mensa FJ, Chen YJ, Lei Y, Lawitz E, Asselah T. Adherence to pan-genotypic glecaprevir/pibrentasvir and efficacy in HCV-infected patients: A pooled analysis of clinical trials. Liver Int. 2020 Apr;40(4):778-786. doi: 10.1111/liv.14266. Epub 2019 Oct 18.
• 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.
• Gane E, Poordad F, Zadeikis N, Valdes J, Lin CW, Liu W, Asatryan A, Wang S, Stedman C, Greenbloom S, Nguyen T, Elkhashab M, Wörns 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.
• 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.
• Foster GR, Dore GJ, Wang S, Grebely J, Sherman KE, Baumgarten A, Conway B, Jackson D, Asselah T, Gschwantler M, Tomasiewicz K, Aguilar H, Asatryan A, Hu Y, Mensa FJ. Glecaprevir/pibrentasvir in patients with chronic HCV and recent drug use: An integrated analysis of 7 phase III studies. Drug Alcohol Depend. 2019 Jan 1;194:487-494. doi: 10.1016/j.drugalcdep.2018.11.007. Epub 2018 Nov 24.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 17, 2017): 703
• Original Estimated Enrollment (submitted: November 11, 2015): 600
• Actual Study Completion Date: January 2017
• Actual Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Male or female, at least 18 years of age at time of screening.
• Screening laboratory result indicating hepatitis C virus (HCV) genotype 1 (GT1) infection.
• Chronic HCV infection.
• Subject must be HCV treatment-naïve (i.e., patient has never received a single dose of any approved or investigational regimen) or treatment-experienced (has failed prior interferon [IFN] or pegylated IFN (pegIFN) with or without ribivarin (RBV), or sofosbuvir (SOF) plus RBV with or without pegIFN therapy).
• Subjects must be non-cirrhotic.

Additional Inclusion Criteria for HCV GT1/human immununovirus type 1 (HIV-1) co-infected patients:

• HIV-1 antiretroviral treatment (ART) naïve with CD4 ≥ 500 cells/mm3 (or CD4+ % ≥ 29%) at Screening and plasma HIV-1 RNA <1,000 copies/mL at Screening and at least once during the 12 months prior to Screening.

OR

• On a stable, qualifying HIV-1 ART regimen for at least 8 weeks prior to screening, with CD4 ≥ 200 cells/mm3 (or CD4+ % ≥14%) at Screening and plasma HIV-1 RNA < LLOQ at Screening and at least once during the 12 months prior to Screening.

Exclusion Criteria:

• History of severe, life-threatening or other significant sensitivity to any excipients of the study drugs.
• 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).
• HCV genotype performed during screening indicating co-infection with more than one HCV genotype.
• Chronic HIV type 2 (HIV-2) infection.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided
• Removed Location Countries: Australia, Austria, Belgium, Canada, Chile, France, Germany, Hungary, Israel, Italy, Korea, Republic of, Lithuania, Mexico, New Zealand, Poland, Portugal, Puerto Rico, Romania, Russian Federation, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT02604017
• Other Study ID Numbers: M13-590; 2015-002087-17 ( EudraCT Number )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: AbbVie
• Study Sponsor: AbbVie
• Collaborators: Not Provided

Investigators

• Study Director: AbbVie Inc.; AbbVie

• PRS Account: AbbVie
• Verification Date: July 2021