A Study to Evaluate Long-term Outcomes Following Treatment With ABT-450/Ritonavir/ABT-267 (ABT-450/r/ABT-267) and ABT-333 With or Without Ribavirin (RBV) in Adults With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection

NCT02167945 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: M14-222
• Study Type: interventional
• Target: 615
• Locations: 1 country
• Sites: 48

Brief Summary

The purpose of this study was to evaluate the effect of treatment with ABT-450 co-formulated with ritonavir and ABT-267 (ABT-450/r/ABT-267) and ABT-333; 3-DAA regimen, with or without ribavirin (RBV) in adults with chronic hepatitis C virus genotype 1 (HCV GT1) infection.

Conditions

Chronic Hepatitis C Virus (HCV) Infection Genotype 1

Keywords

Hepatitis C Genotype 1; Compensated Cirrhosis; Cirrhosis; Naïve; Hepatitis C; Hepatitis C Virus; Treatment-Experienced; Relapser; Null responder; Non responder

Outcome Measures

Primary Outcomes (6)

• All-Cause Death: Time to Event

  Time to all-cause death was defined as the number of days from the first day of study drug dosing for the participant to the date of death. All deaths were to be included, regardless of whether the death occurred while the participant was still taking study drug or had previously discontinued study drug. If the participant did not die, their data was to be censored at the date of their last available assessment of clinical outcomes. For participants with no post-baseline assessment, the participant's data was to be censored on the first day of study drug dosing. The event-free survival rates were estimated using Kaplan-Meier methodology and incidence estimates are presented with 95% confidence intervals. The pre-specified analysis of all-cause death included pooled data from TOPAZ-II (this study) and the companion study TOPAZ-I (M14-423; NCT02219490).

  At Post-Treatment Weeks 52, 104, 156, 208, and 260

• Liver-Related Death: Time to Event

  Time to liver-related death was defined as number of days from the 1st day of study drug dosing for the participant to date of liver-related death. All liver-related deaths were to be included, regardless of whether the death occurred while the participant was still taking study drug or had previously discontinued study drug. If the participant didn't experience the event of interest nor had died (all-cause death), their data was to be censored at the date of their last available assessment of clinical outcomes. For participants with no post-baseline assessment, their data was to be censored on the 1st day of study drug dosing. All-cause death was a censoring event for liver-related death. The event-free survival rates were estimated using Kaplan-Meier methodology and incidence estimates are presented with 95% confidence intervals. The pre-specified analysis of liver-related death included pooled data from TOPAZ-II (this study) and the companion study TOPAZ-I (M14-423; NCT02219490).

  At Post-Treatment Weeks 52, 104, 156, 208, and 260

• Liver Decompensation: Time to Event

  Time to liver decompensation was defined as number of days from the 1st day of study drug dosing for the participant to the date of liver decompensation. All liver decompensation was to be included, regardless of whether it occurred while the participant was still taking study drug or had previously discontinued study drug. If the participant didn't experience the event of interest nor had died (all-cause death), their data was to be censored at the date of their last available assessment of clinical outcomes. For participants with no post-baseline assessment, their data was to be censored on the 1st day of study drug dosing. All-cause death was a censoring event for liver decompensation. The event-free survival rates were estimated using Kaplan-Meier methodology and incidence estimates are presented with 95% confidence intervals. The pre-specified analysis of liver decompensation included pooled data from TOPAZ-II (this study) and the companion study TOPAZ-I (M14-423; NCT02219490).

  At Post-Treatment Weeks 52, 104, 156, 208, and 260

• Liver Transplantation: Time to Event

  Time to liver transplantation was defined as number of days from the 1st day of study drug dosing for the participant to date of liver transplantation. All liver transplantation was to be included, regardless of whether it occurred while the participant was still taking study drug or had previously discontinued study drug. If the participant didn't experience the event of interest nor had died (all-cause death), their data was to be censored at the date of their last available assessment of clinical outcomes. For participants with no post-baseline assessment, their data was to be censored on the 1st day of study drug dosing. All-cause death was a censoring event for liver transplantation. The event-free survival rates were estimated using Kaplan-Meier methodology and incidence estimates are presented with 95% confidence intervals. The pre-specified analysis of liver transplantation included pooled data from TOPAZ-II (this study) and the companion study TOPAZ-I (M14-423; NCT02219490).

  At Post-Treatment Weeks 52, 104, 156, 208, and 260

• Hepatocellular Carcinoma: Time to Event

  Time to hepatocellular carcinoma was defined as number of days from the 1st day of study drug dosing for the participant to date of hepatocellular carcinoma. All hepatocellular carcinoma was to be included, whether it occurred while the participant was still taking study drug or had previously discontinued study drug. If the participant didn't experience the event of interest nor had died (all-cause death), their data was to be censored at the date of their last available assessment of clinical outcomes. For those with no post-baseline assessment, their data was to be censored on the 1st day of study drug dosing. All-cause death was a censoring event for hepatocellular carcinoma. The event-free survival rates were estimated using Kaplan-Meier methodology and incidence estimates are presented with 95% confidence intervals. The pre-specified analysis of hepatocellular carcinoma included pooled data from TOPAZ-II (this study) and the companion study TOPAZ-I (M14-423; NCT02219490).

  At Post-Treatment Weeks 52, 104, 156, 208, and 260

• All-Cause Death, Liver-Related Death, Liver Decompensation, Liver Transplantation, Hepatocellular Carcinoma: Time to Event

  Time to the composite of clinical outcomes is the time to the first occurrence of all-cause death, liver-related death, liver decompensation, liver transplantation, or hepatocellular carcinoma. All first occurrences were to be included, regardless of whether it occurred while the participant was still taking study drug or had previously discontinued study drug. If the participant did not experience any of these events, their data was to be censored at the date of their last available assessment of clinical outcomes. For participants with no post-baseline assessment, the participant's data was to be censored on the first day of study drug dosing. The event-free survival rates were estimated using Kaplan-Meier methodology and incidence estimates are presented with 95% confidence intervals. Pre-specified analysis included pooled data from this study and from TOPAZ-I; NCT02219490.

  At Post-Treatment Weeks 52, 104, 156, 208, and 260

Secondary Outcomes (5)

• Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12)

  12 weeks after the last actual dose of study drug

• Mean Change From Baseline in Short Form 36 Version 2.0 (SF-36 V2) Physical Component Summary (PCS) Score at Post-Treatment Week 12 and Post-Treatment Week 24

  From Baseline to Post-Treatment Week 12 and Post-Treatment Week 24

• Mean Change From Baseline in Short Form 36 Version 2.0 (SF-36 V2) Mental Component Summary (MCS) Score at Post-Treatment Week 12 and Post-Treatment Week 24

  From Baseline to Post-Treatment Week 12 and Post-Treatment Week 24

• Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Total Score at Post-Treatment Week 12 and Post-Treatment Week 24

  From Baseline to Post-Treatment Week 12 and Post-Treatment Week 24

• Treatment Compliance: Percentage of Tablets Taken Relative to the Total Tablets

  Up to Treatment Week 24

Study Arms (1)

ABT-450/r/ABT-267 plus ABT-333 with or without ribavirin (RBV)

EXPERIMENTAL

Participants with HCV GT1b without cirrhosis received the 3-DAA (ABT-450/ritonavir/ABT-267 and ABT-333) regimen: two 75 mg ABT-450/50 mg ritonavir/12.5 mg ABT-267 tablets taken orally every morning (QD) and one ABT-333 250 mg tablet taken orally twice a day (BID) for 12 weeks. Participants with HCV GT1a without cirrhosis and those with HCV GT1b with cirrhosis received the 3-DAA regimen and weight-based ribavirin (RBV; 1000 to 1200 mg divided twice daily per local label) for 12 weeks. Participants with HCV GT1a with cirrhosis received the 3-DAA regimen and weight-based RBV per local label for 24 weeks.

Drug: ABT-450/r/ABT-267; Drug: ABT-333; Drug: Ribavirin (RBV)

Interventions

ABT-450/r/ABT-267 DRUG

Tablet for oral use

Also known as: ABT-450 also known as paritaprevir, ABT-267 also known as ombitasvir, Paritaprevir/ritonavir/ombitasvir also known as Viekirax

ABT-450/r/ABT-267 plus ABT-333 with or without ribavirin (RBV)

ABT-333 DRUG

Tablet for oral use

Also known as: ABT-333 also known as dasabuvir, ABT-333 also known as Exviera

ABT-450/r/ABT-267 plus ABT-333 with or without ribavirin (RBV)

Ribavirin (RBV) DRUG

Ribavirin was provided as 200 mg tablets, and dosed based on weight, 1000 to 1200 mg divided twice daily per local label. For example, for participants weighing \< 75 kg, RBV may have been taken orally as 2 tablets in the morning and 3 tablets in the evening which corresponds to a 1000 mg total daily dose. For participants weighing ≥ 75 kg, RBV may have been taken orally as 3 tablets in the morning and 3 tablets in the evening which corresponds to a 1200 mg total daily dose.

ABT-450/r/ABT-267 plus ABT-333 with or without ribavirin (RBV)

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Females must be post-menopausal for more than 2 years or surgically sterile or practicing specific forms of birth control
• Chronic hepatitis C, genotype 1-infection (HCV RNA level greater than 1,000 IU/mL at screening)
• HCV genotype 1 infection per screening laboratory result

You may not qualify if:

• Use of contraindicated medications within 2 weeks of dosing
• Abnormal laboratory tests
• Positive hepatitis B surface antigen and anti-Human Immunodeficiency Virus Antibody
• History of solid organ transplant, clinical evidence of Child-Pugh B or C classification or clinical history of liver decompensation
• Presence of hepatocellular carcinoma at screening

Sponsors & Collaborators

• AbbVie: lead

Study Sites (48)

St. Josephs Hospital and Med Center /ID# 127800

Phoenix, Arizona, 85013, United States

Location

Franco Felizarta, Md /Id# 126569

Bakersfield, California, 93301, United States

Location

Ruane Clinical Research Group /ID# 126577

Los Angeles, California, 90036, United States

Location

California Pacific Medical Center /ID# 128681

San Francisco, California, 94115, United States

Location

Univ of Colorado Cancer Center /ID# 126568

Aurora, Colorado, 80045, United States

Location

Medstar Health Research Institute /ID# 128683

Washington D.C., District of Columbia, 20010, United States

Location

Bach and Godofsky Infec Dis /ID# 128685

Bradenton, Florida, 34209, United States

Location

University of Florida - Archer /ID# 127787

Gainesville, Florida, 32610, United States

Location

Encore Borland-Groover Clinical Research /Id# 127781

Jacksonville, Florida, 32256, United States

Location

University of Miami /ID# 127622

Miami, Florida, 33136, United States

Location

South Florida Ctr Gastro, P.A. /ID# 126567

Wellington, Florida, 33414, United States

Location

Atlanta Gastro Assoc /ID# 126571

Atlanta, Georgia, 30342, United States

Location

Northwestern University Feinberg School of Medicine /ID# 128684

Chicago, Illinois, 60611-2927, United States

Location

The University of Chicago Medical Center /ID# 126576

Chicago, Illinois, 60637-1443, United States

Location

Duplicate_Indiana University Health /ID# 126573

Indianapolis, Indiana, 46202, United States

Location

Tulane University /ID# 127779

New Orleans, Louisiana, 70112-2699, United States

Location

Louisana Research Center, LLC /ID# 126561

Shreveport, Louisiana, 71105-6800, United States

Location

Johns Hopkins University /ID# 127791

Baltimore, Maryland, 21287, United States

Location

Digestive Disease Associates - Catonsville /ID# 127624

Catonsville, Maryland, 21228, United States

Location

Beth Israel Deaconess Medical Center /ID# 126560

Boston, Massachusetts, 02215-5400, United States

Location

Henry Ford Health System /ID# 127783

Detroit, Michigan, 48202, United States

Location

Minnesota Gastroenterology PA /ID# 126579

Plymouth, Minnesota, 55446, United States

Location

St. Louis University /ID# 126564

St Louis, Missouri, 63104, United States

Location

AGA Clinical Research Associates, LLC /ID# 126578

Egg Harbor, New Jersey, 08234, United States

Location

Rutgers New Jersey School of Medicine /ID# 128686

Newark, New Jersey, 07103, United States

Location

University of New Mexico /ID# 128859

Albuquerque, New Mexico, 87102-4517, United States

Location

Southwest Care Center /ID# 127784

Santa Fe, New Mexico, 87505, United States

Location

North Shore University Hospital /ID# 126565

New Hyde Park, New York, 11040, United States

Location

The Mount Sinai Hospital /ID# 128682

New York, New York, 10029, United States

Location

Columbia Univ Medical Center /ID# 126566

New York, New York, 10032-3725, United States

Location

Columbia Univ Medical Center /ID# 127621

New York, New York, 10032-3725, United States

Location

Premier Medical Group - GI Division /ID# 127793

Poughkeepsie, New York, 12601, United States

Location

Univ Rochester Med Ctr /ID# 127655

Rochester, New York, 14642, United States

Location

Atrium Health Carolinas Medical Center /ID# 127632

Charlotte, North Carolina, 28203, United States

Location

Carolinas Center For Liver Dis /ID# 127788

Statesville, North Carolina, 28677, United States

Location

University of Cincinnati Physicians Company, LLC /ID# 127790

Cincinnati, Ohio, 45267-2827, United States

Location

Options Health Research, LLC /ID# 127630

Tulsa, Oklahoma, 74104, United States

Location

University Gastroenterology /ID# 127789

Providence, Rhode Island, 02905, United States

Location

Gastro One /ID# 127792

Germantown, Tennessee, 38138, United States

Location

Inquest Clinical Research /ID# 126574

Baytown, Texas, 77521-2415, United States

Location

Cure C Consortium /ID# 126570

Houston, Texas, 77004, United States

Location

Liver Associates of Texas, P.A /ID# 126563

Houston, Texas, 77030-2783, United States

Location

Austin Institute for Clinical Research /ID# 126562

Pflugerville, Texas, 78660, United States

Location

TX Liver Inst, Americ Res Corp /ID# 127623

San Antonio, Texas, 78215, United States

Location

Clinical Research Ctrs America /ID# 127780

Murray, Utah, 84123, United States

Location

Virginia Mason - Seattle Orthapedics /ID# 130288

Seattle, Washington, 98101, United States

Location

University of Washington /ID# 127785

Seattle, Washington, 98109, United States

Location

Dean Clinic /ID# 126575

Madison, Wisconsin, 53715, United States

Location

MeSH Terms

Conditions

Hepatitis C, Chronic; Hepatitis C; Fibrosis

Interventions

paritaprevir; ombitasvir; dasabuvir; Ribavirin

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)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Global Medical Services
• Organization: AbbVie

abbvieclinicaltrials@abbvie.com

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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2014
• First Posted: June 19, 2014
• Study Start: June 12, 2014
• Primary Completion: May 13, 2021
• Study Completion: May 13, 2021
• Last Updated: July 19, 2022
• Results First Posted: April 6, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: For details on when studies are available for sharing, please refer to the link below.
• Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Use Agreement (DUA). For more information on the process, or to submit a request, visit the following link.

Locations

US (48)