Ombitasvir/ABT-450/Ritonavir and Dasabuvir With or Without Ribavirin in HCV Genotype 1-Infected Adults With Chronic Kidney Disease

• Sponsor: AbbVie (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02207088
• Collaborator: (none)
• Enrollment: 68
• Arm: 1
• Actual Duration (Months): 26.4

Study Details

Study Description

Brief Summary

This open-label study will evaluate safety, pharmacokinetics and efficacy of a 12 or 24-week regimen of ombitasvir/paritaprevir/ritonavir and dasabuvir with or without ribavirin in HCV-genotype 1-infected subjects with an Estimated Glomerular Filtration Rate (eGFR) <30, including those on hemodialysis or peritoneal dialysis.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis C; Hepatitis C Virus; Compensated Cirrhosis; Severe Renal Impairment; End-stage Renal Disease	Drug: ombitasvir/paritaprevir/ritonavir; Drug: dasabuvir; Drug: Ribavirin	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 68 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label Study to Evaluate the Safety and Efficacy of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir With or Without Ribavirin (RBV) in Adults With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection, With Severe Renal Impairment or End-Stage Renal Disease (RUBY-I)
• Actual Study Start Date: Sep 23, 2014
• Actual Primary Completion Date: Dec 6, 2016
• Actual Study Completion Date: Dec 6, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 3-DAA (Direct Acting Antivirals) with or without RBV 3-DAA (ombitasvir/paritaprevir/ritonavir 25 mg/150 mg/100 mg once daily [QD] and dasabuvir 250 mg twice daily [BID]) with or without ribavirin (RBV; dosed divided twice a day) for 12 or 24 weeks	Drug: ombitasvir/paritaprevir/ritonavir; tablet; Other Names: ABT-450/r/ABT-267 Viekira Pak paritaprevir also known as ABT-450 ombitasvir also known as ABT-267 dasabuvir also known as ABT-333 ; Drug: dasabuvir; tablet; Other Names: ABT-333 ; Drug: Ribavirin; tablet; Other Names: RBV

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Sustained Virologic Response 12 (SVR12) Weeks Post-treatment [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.

Secondary Outcome Measures

1. Percentage of Participants With On-treatment Virologic Failure [Up to 24 weeks]

   On-treatment virologic failure was defined as confirmed HCV RNA ≥ LLOQ after < LLOQ during treatment, confirmed increase of > 1 log (subscript)10(subscript) IU/mL above the lowest value post-baseline HCV RNA during treatment, or HCV RNA ≥ LLOQ persistently during treatment with at least 6 weeks of treatment.

2. Percentage of Participants With Post-Treatment Relapse [Within 12 weeks after the last dose of study drug]

   Post-treatment relapse was defined as confirmed HCV RNA ≥ LLOQ between end of treatment and 12 weeks after the last dose of study drug among participants completing treatment and with HCV RNA < LLOQ at the end of treatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Positive for anti-HCV Ab (Antibody) and HCV RNA >1,000 IU/mL at Screening.

2. Screening laboratory result indicating HCV genotype 1 infection.

3. Subject has never received antiviral treatment for hepatitis C infection (treatment-naive subject) or subject has received previous treatment with peginterferon with or without RBV with non-response (HCV RNA quantifiable at end of treatment or relapsed after end of treatment).

4. Estimated Glomerular Filtration Rate (eGFR) < 30 mL/min/1.73 m^2 as estimated by the Modification of Diet in Renal Disease (MDRD) method.

Exclusion Criteria:

1. Women who are pregnant or breastfeeding.

2. Positive test result for Hepatitis B surface antigen (HBsAg) or anti-Human Immunodeficiency Virus (HIV Ab).

3. Any current or past clinical evidence of Child-Pugh B or C classification or clinical history of liver decompensation such as ascites (noted on physical exam), variceal bleeding, or hepatic encephalopathy.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• AbbVie

Investigators

• Study Director: Eric Cohen, MD, AbbVie

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT02207088
• Other Study ID Numbers: M14-226; 2014-001527-77
• First Posted: Aug 1, 2014
• Last Update Posted: Nov 9, 2017
• Last Verified: Oct 1, 2017

• Keywords provided by AbbVie: Chronic Hepatitis C; Hepatitis C; End-stage renal disease; Hepatitis C Genotype 1; Severe Renal Impairment; renal disease; Compensated Cirrhosis; Renal impairment; dialysis; Hepatitis C Virus; cirrhosis
• Additional relevant MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic; Liver Cirrhosis; Kidney Diseases; Kidney Failure, Chronic; Renal Insufficiency; Fibrosis; Ritonavir; Ribavirin

Study Results

Participant Flow

Pre-assignment Detail	The intent-to-treat (ITT) population consisted of all enrolled participants who received at least 1 dose of study drug.

Arm/Group Title	3-DAA ± RBV
Arm/Group Description	3-DAA (ombitasvir/paritaprevir/ritonavir 25 mg/150 mg/100 mg once daily [QD] and dasabuvir 250 mg twice daily [BID]) with or without ribavirin (RBV; dosed divided twice a day) for 12 or 24 weeks
Period Title: Overall Study
STARTED	68
COMPLETED	66
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	3-DAA ± RBV
Arm/Group Description	3-DAA (ombitasvir/paritaprevir/ritonavir 25 mg/150 mg/100 mg once daily [QD] and dasabuvir 250 mg twice daily [BID]) with or ribavirin (RBV; dosed divided twice a day) for 12 or 24 weeks
Overall Participants	68
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.4 (7.00)
Sex: Female, Male (Count of Participants)
Female	11 16.2%
Male	57 83.8%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Sustained Virologic Response 12 (SVR12) Weeks Post-treatment
Description	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.
Time Frame	12 weeks after the last actual dose of study drug

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug (ITT population).

Arm/Group Title	3-DAA ± RBV
Arm/Group Description	3-DAA (ombitasvir/paritaprevir/ritonavir 25 mg/150 mg/100 mg once daily [QD] and dasabuvir 250 mg twice daily [BID]) with or without ribavirin (RBV; dosed divided twice a day) for 12 or 24 weeks
Measure Participants	68
Number (95% Confidence Interval) [percentage of participants]	94.1 138.4%

2. Secondary Outcome

Title	Percentage of Participants With On-treatment Virologic Failure
Description	On-treatment virologic failure was defined as confirmed HCV RNA ≥ LLOQ after < LLOQ during treatment, confirmed increase of > 1 log (subscript)10(subscript) IU/mL above the lowest value post-baseline HCV RNA during treatment, or HCV RNA ≥ LLOQ persistently during treatment with at least 6 weeks of treatment.
Time Frame	Up to 24 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug (ITT population).

Arm/Group Title	3-DAA ± RBV
Arm/Group Description	3-DAA (ombitasvir/paritaprevir/ritonavir 25 mg/150 mg/100 mg once daily [QD] and dasabuvir 250 mg twice daily [BID]) with or without ribavirin (RBV; dosed divided twice a day) for 12 or 24 weeks
Measure Participants	68
Number (95% Confidence Interval) [percentage of participants]	0 0%

3. Secondary Outcome

Title	Percentage of Participants With Post-Treatment Relapse
Description	Post-treatment relapse was defined as confirmed HCV RNA ≥ LLOQ between end of treatment and 12 weeks after the last dose of study drug among participants completing treatment and with HCV RNA < LLOQ at the end of treatment.
Time Frame	Within 12 weeks after the last dose of study drug

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug (ITT population) with HCV RNA < LLOQ at the end of treatment and completed treatment.

Arm/Group Title	3-DAA ± RBV
Arm/Group Description	3-DAA (ombitasvir/paritaprevir/ritonavir 25 mg/150 mg/100 mg once daily [QD] and dasabuvir 250 mg twice daily [BID]) with or without ribavirin (RBV; dosed divided twice a day) for 12 or 24 weeks
Measure Participants	65
Number (95% Confidence Interval) [percentage of participants]	1.5 2.2%

Adverse Events

Time Frame	Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 28 weeks).
Adverse Event Reporting Description	TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.
Arm/Group Title	3-DAA +/- RBV
Arm/Group Description	3-DAA (ombitasvir/paritaprevir/ritonavir 25 mg/150 mg/100 mg once daily [QD] and dasabuvir 250 mg twice daily [BID]) with or without ribavirin (RBV; dosed divided twice a day) for 12 or 24 weeks
All Cause Mortality
	3-DAA +/- RBV
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	3-DAA +/- RBV
	Affected / at Risk (%)	# Events
Total	17/68 (25%)
Blood and lymphatic system disorders
ANAEMIA	1/68 (1.5%)
LEUKOCYTOSIS	1/68 (1.5%)
Cardiac disorders
ANGINA PECTORIS	1/68 (1.5%)
CARDIAC ARREST	1/68 (1.5%)
CARDIAC TAMPONADE	1/68 (1.5%)
CARDIO-RESPIRATORY ARREST	1/68 (1.5%)
CORONARY ARTERY DISEASE	1/68 (1.5%)
LEFT VENTRICULAR DYSFUNCTION	1/68 (1.5%)
Gastrointestinal disorders
DIARRHOEA	1/68 (1.5%)
DYSPHAGIA	1/68 (1.5%)
SMALL INTESTINAL OBSTRUCTION	1/68 (1.5%)
VOLVULUS	1/68 (1.5%)
Hepatobiliary disorders
LIVER INJURY	1/68 (1.5%)
Infections and infestations
ARTERIOVENOUS GRAFT SITE INFECTION	1/68 (1.5%)
INTERVERTEBRAL DISCITIS	1/68 (1.5%)
PERITONITIS BACTERIAL	1/68 (1.5%)
PNEUMONIA	2/68 (2.9%)
STAPHYLOCOCCAL INFECTION	1/68 (1.5%)
Injury, poisoning and procedural complications
VASCULAR PSEUDOANEURYSM	1/68 (1.5%)
Metabolism and nutrition disorders
HYPERKALAEMIA	1/68 (1.5%)
HYPOGLYCAEMIA	1/68 (1.5%)
Nervous system disorders
LOSS OF CONSCIOUSNESS	1/68 (1.5%)
SYNCOPE	1/68 (1.5%)
Psychiatric disorders
MENTAL STATUS CHANGES	1/68 (1.5%)
Respiratory, thoracic and mediastinal disorders
ACUTE RESPIRATORY FAILURE	1/68 (1.5%)
PLEURAL EFFUSION	1/68 (1.5%)
RESPIRATORY FAILURE	1/68 (1.5%)
Vascular disorders
ACCELERATED HYPERTENSION	1/68 (1.5%)
HYPERTENSIVE CRISIS	1/68 (1.5%)
Other (Not Including Serious) Adverse Events
	3-DAA +/- RBV
	Affected / at Risk (%)	# Events
Total	51/68 (75%)
Blood and lymphatic system disorders
ANAEMIA	26/68 (38.2%)
Gastrointestinal disorders
DIARRHOEA	13/68 (19.1%)
NAUSEA	13/68 (19.1%)
VOMITING	10/68 (14.7%)
General disorders
FATIGUE	20/68 (29.4%)
OEDEMA PERIPHERAL	5/68 (7.4%)
Investigations
HAEMOGLOBIN DECREASED	9/68 (13.2%)
Metabolism and nutrition disorders
DECREASED APPETITE	6/68 (8.8%)
Nervous system disorders
DIZZINESS	6/68 (8.8%)
HEADACHE	8/68 (11.8%)
Skin and subcutaneous tissue disorders
PRURITUS	8/68 (11.8%)
Vascular disorders
HYPERTENSION	4/68 (5.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.