A Study Comparing Efficacy and Safety of ABT-493/ABT-530 to Sofosbuvir Dosed With Daclatasvir in Adults With HCV Genotype 3 Infection

NCT02640157 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: M13-5942015-002272-24
• Study Type: interventional
• Target: 506
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study was to compare the safety and efficacy of ABT-493/ABT-530 to the combination of sofosbuvir (SOF) and daclatasvir (DCV) in adults with genotype 3 (GT3) chronic hepatitis C virus (HCV) infection.

Conditions

Chronic Hepatitis C; Hepatitis C Virus; Genotype 3 Hepatitis C Virus

Keywords

interferon free; Hepatitis C; daclatasvir; Sovaldi; HCV; Hepatitis C Virus; Hepatitis C Genotype 3; Hep C; sofosbuvir; Chronic Hepatitis C; Daklinza

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12): Noninferiority of Arm A to Arm B

  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 in the percentage of participants achieving SVR12 of the 12-week regimen (Arm A) to the standard of care (Arm B: 12 weeks of treatment with sofosbuvir \[SOF\] + daclatasvir \[DCV\]), defined as: a) the lower bound of the 95% confidence interval (CI) for the difference was above the non-inferiority margin of -6% and the lower bound of the 95% CI for the SVR12 rate within Arm A was greater than 92%; OR b) the lower bound of the 95% CI for the difference was below the non-inferiority margin of -6% and the lower bound of the 97.5% CI for the SVR12 rate within Arm A was greater than 92%; OR c) the lower bound of the 97.5% CI for the difference was above the non-inferiority margin of -6% and the lower bound of the 95% CI for the SVR12 rate within Arm A was below 92%.

  12 weeks after the last actual dose of study drug

• Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12): Noninferiority of Arm C to Arm A

  SVR12 was defined as plasma HCV RNA level \<LLOQ 12 weeks after the last dose of study drug. If the first primary efficacy objective (noninferiority of Arm A to Arm B) was achieved, then the second primary efficacy objective, noninferiority in the percentage of participants achieving SVR12 of the 8-week regimen (Arm C) to the 12-week regimen (Arm A) was to be tested. Noninferiority was defined as: a) the lower bound of the 95% CI for the difference was above the noninferiority margin of -6% and the lower bound of the 95% CI for the SVR12 rate within Arm C was greater than 92%, OR b) the lower bound of the 95% CI for the difference was below the noninferiority margin of -6% and the lower bound of the 97.5% CI for the SVR12 rate within Arm C was greater than 92%, OR c) the lower bound of the 97.5% CI for the difference was above the noninferiority margin of -6% and the lower bound of the 95% CI for the SVR12 rate within Arm C was below 92%.

  12 weeks after the last actual dose of study drug

Secondary Outcomes (3)

• Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12): Superiority of Arm A to Arm B

  12 weeks after the last actual dose of study drug

• Percentage of Participants With On-treatment Virologic Failure

  Treatment weeks 1, 2, 4, 8 (end of treatment for Arm C), and 12 (end of treatment for Arms A and B) 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 (3)

Arm A

EXPERIMENTAL

ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks.

Drug: ABT-493/ABT-530

Arm B

ACTIVE COMPARATOR

Sofosbuvir 400 mg once daily (QD) co-administered with daclatasvir 60 mg QD for 12 weeks.

Drug: Sofosbuvir; Drug: Daclatasvir

Arm C

EXPERIMENTAL

ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 8 weeks.

Drug: ABT-493/ABT-530

Interventions

ABT-493/ABT-530 DRUG

Tablet; ABT-493 coformulated with ABT-530

Also known as: ABT-493 also known as glecaprevir, ABT-530 also known as pibrentasvir, MAVYRET

Arm A; Arm C

Sofosbuvir DRUG

Tablet

Also known as: Sovaldi

Arm B

Daclatasvir DRUG

Tablet

Also known as: Daklinza

Arm B

Eligibility Criteria

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

You may qualify if:

• Male or female (of nonchildbearing potential, practicing total abstinence, sexually active with female partners only, or using allowed contraceptive methods) at least 18 years of age at time of screening.
• Screening laboratory result indicating HCV GT3 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; or
• A liver biopsy consistent with chronic HCV infection; or
• Abnormal alanine aminotransferase (ALT) levels for at least 6 months before screening.
• Hepatitis C virus treatment-naïve (i.e., participant had never received any anti-HCV treatment).
• Documented as noncirrhotic.

You may not qualify if:

• 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 have precluded 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 Ab (HIV Ab).
• Hepatitis C virus genotyping performed during screening indicated co-infection with more than one HCV genotype.
• Any cause of liver disease other than chronic HCV infection.
• Consideration by the investigator, for any reason, that the participant was an unsuitable candidate to receive ABT-493/ABT-530, SOF, or DCV.
• History of severe, life-threatening, or other significant sensitivity to any excipients of the study drug.
• Previous use of any anti-HCV treatment.

Sponsors & Collaborators

• AbbVie: lead

Related Publications (6)

• Zeuzem S, Foster GR, Wang S, Asatryan A, Gane E, Feld JJ, Asselah T, Bourliere 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.

  PMID: 29365309 BACKGROUND

• Brown A, Welzel TM, Conway B, Negro F, Brau 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.

  PMID: 31568620 DERIVED

• 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

• 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.

  PMID: 30529905 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

Related Links

• Related info

MeSH Terms

Conditions

Hepatitis C, Chronic; Hepatitis C

Interventions

glecaprevir; pibrentasvir; glecaprevir and pibrentasvir; Sofosbuvir; daclatasvir

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

Intervention Hierarchy (Ancestors)

Uridine Monophosphate; Uracil Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides

Results Point of Contact

• Title: Global Medical Services
• Organization: AbbVie

800-633-9110

Study Officials

• AbbVie Inc

  AbbVie

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2015
• First Posted: December 28, 2015
• Study Start: December 1, 2015
• Primary Completion: October 1, 2016
• Study Completion: February 1, 2017
• Last Updated: July 30, 2021
• Results First Posted: September 15, 2017

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share