Ombitasvir/Paritaprevir/Ritonavir With or Without Dasabuvir in Adults With Genotype 1a or Genotype 4 Chronic Hepatitis C Virus (HCV) Infection, With Severe Kidney Impairment or End Stage Kidney Disease

• ClinicalTrials.gov Identifier: NCT02487199
• Recruitment Status: Completed
• First Posted: July 1, 2015
• Results First Posted: December 4, 2017
• Last Update Posted: December 4, 2017
• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

Study Description

Brief Summary:

This study evaluates the efficacy and safety of ombitasvir/paritaprevir/ritonavir with or without dasabuvir in adults with hepatitis C virus (HCV) genotype 1a (GT1a) or genotype 4 (GT4) infection and with severe kidney impairment or end-stage kidney disease.

Condition or disease	Intervention/treatment	Phase
Hepatitis C Virus (HCV)	Drug: ombitasvir/paritaprevir/ritonavir and dasabuvir; Drug: ombitasvir/paritaprevir/ritonavir	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 18 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label Study to Evaluate the Safety and Efficacy of Ombitasvir/Paritaprevir/Ritonavir With or Without Dasabuvir in Adults With Genotype 1a or Genotype 4 Chronic Hepatitis C Virus (HCV) Infection, With Severe Renal Impairment or End-Stage Renal Disease (RUBY-II)
• Actual Study Start Date: September 30, 2015
• Actual Primary Completion Date: December 5, 2016
• Actual Study Completion Date: December 5, 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: HCV GT1a (3-DAA); Participants with hepatitis C virus (HCV) genotype 1a (GT1a) infection received 3-direct-acting antiviral agent (3-DAA: ombitasvir/paritaprevir/ritonavir [25 mg/150 mg/100 mg once daily] and dasabuvir [250 mg twice daily]) for 12 weeks.	Drug: ombitasvir/paritaprevir/ritonavir and dasabuvir; Tablet; ombitasvir coformulated with paritaprevir and ritonavir, dasabuvir tablet; Other Name: Viekira Pak, paritaprevir also known as ABT-450, ombitasvir also known as ABT-267, dasabuvir also known as ABT-333
Experimental: HCV GT4 (2-DAA); Participants with hepatitis C virus (HCV) genotype 4 (GT4) infection received 2-direct-acting antiviral agent (2-DAA: ombitasvir/paritaprevir/ritonavir [25 mg/150 mg/100 mg once daily]) for 12 weeks.	Drug: ombitasvir/paritaprevir/ritonavir; Tablet; ombitasvir coformulated with paritaprevir and ritonavir; Other Name: Technivie, paritaprevir also known as ABT-450, ombitasvir also known as ABT-267

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) [ 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. Participants with missing data after backward imputation were imputed as nonresponders.
2. Number of Participants With Adverse Events [ Time Frame: Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 16 weeks) ]
   An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each event to the use of study drug as either reasonable possibility or no reasonable possibility. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the subject and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent events (TEAEs/TESAEs) are defined as any event that began or worsened in severity from first dose of study drug until 30 days after the last dose. For more details on AEs please see the Adverse Event section.

Secondary Outcome Measures :

1. Percentage of Participants With On-treatment Virologic Failure [ Time Frame: 12 weeks ]
   On-treatment virologic failure was defined as confirmed HCV RNA ≥ LLOQ after HCV RNA < LLOQ during treatment or confirmed increase of > 1 log(subscript)10(subscript) IU/mL above the lowest value post-baseline in HCV RNA during treatment with at least 6 weeks of treatment.
2. 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Chronic hepatitis C virus (HCV) genotype 1a (GT1a) infection or genotype 4 (GT4) infection (HCV RNA level greater than 1,000 IU/mL at Screening).
• Females must be post-menopausal, of non-child bearing potential or practicing specific forms of birth control.
• Chronic kidney disease stage 4 or stage 5.

Exclusion Criteria:

• Females who are pregnant or breastfeeding
• Positive test result for Hepatitis B surface antigen (HBsAg) or anti-human immunodeficiency virus antibody (HIV Ab)
• HCV genotype performed during screening unable to genotype or co-infection with any other HCV genotype, no mixed genotypes.
• Abnormal laboratory tests
• Current enrollment in another investigational study
• Prior treatment with a direct acting antiviral agent (DAA) containing regimen with the exception of interferon or pegylated interferon with or without ribavirin
• Current treatment with a direct acting antiviral agent (DAA) containing regimen
• Any evidence of liver cirrhosis or liver cancer

Contacts and Locations

Sponsors and Collaborators

AbbVie

Investigators

• Study Director: AbbVie Inc; AbbVie

More Information

Additional Information:

Related Info 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Shuster DL, Menon RM, Ding B, Khatri A, Li H, Cohen E, Jewett M, Cohen DE, Zha J. Effects of chronic kidney disease stage 4, end-stage renal disease, or dialysis on the plasma concentrations of ombitasvir, paritaprevir, ritonavir, and dasabuvir in patients with chronic HCV infection: pharmacokinetic analysis of the phase 3 RUBY-I and RUBY-II trials. Eur J Clin Pharmacol. 2019 Feb;75(2):207-216. doi: 10.1007/s00228-018-2566-6. Epub 2018 Oct 5.

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT02487199
• Other Study ID Numbers: M15-461; 2015-002012-33 ( EudraCT Number )
• First Posted: July 1, 2015
• Results First Posted: December 4, 2017
• Last Update Posted: December 4, 2017
• Last Verified: October 2017

Keywords provided by AbbVie:

hepatitis C infection; hepatitis C; severe kidney disease; chronic kidney disease; Genotype 1a; Genotype 4; treatment experienced; interferon; IFN; pegIFN

Additional relevant MeSH terms:

Infection; Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Kidney Diseases; Liver Diseases; Digestive System Diseases; Hepatitis, Viral, Human; Virus Diseases; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Flaviviridae Infections; Urologic Diseases; Hepatitis, Chronic; Ritonavir; HIV Protease Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-HIV Agents; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors