A Study of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir With or Without Sofosbuvir and Ribavirin in Direct-Acting Antiviral Agent Treatment-Experienced Adults With Chronic Hepatitis C Virus Infection

• Sponsor: AbbVie (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02356562
• Collaborator: (none)
• Enrollment: 29
• Arm: 1
• Actual Duration (Months): 29.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of ombitasvir/paritaprevir/ritonavir and dasabuvir with or without sofosbuvir (SOF) and ribavirin (RBV) in DAA treatment-experienced adults with Genotype 1 Chronic Hepatitis C Virus infection. This study will contain 2 parts.

Part 1: Approximately 20 participants and at least 10 of the 20 participants previously treated with the combination of ombitasvir/paritaprevir/ritonavir and dasabuvir, with or without RBV, and experienced treatment failure.

Part 2: Approximately 10 participants and all participants previously treated with SOF/ledipasvir and experienced treatment failure.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis C Infection	Drug: ombitasvir/paritaprevir/ritonavir and dasabuvir; Drug: Sofosbuvir; Drug: Ribavirin	Phase 2

Detailed Description

Efficacy, safety, and demographic analyses were performed separately for the 2 study parts using the intent-to-treat (ITT) population, which consists of all enrolled participants who received at least one dose of study drug.

Study Design

• Study Type: Interventional
• Actual Enrollment: 29 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, Efficacy, and Pharmacokinetics of Ombitasvir/ABT-450/Ritonavir (Ombitasvir/ABT-450/r) and Dasabuvir Co-administered With or Without Sofosbuvir (SOF) and Ribavirin (RBV) in Direct-Acting Antiviral Agent (DAA) Treatment-Experienced Adults With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection
• Actual Study Start Date: Feb 3, 2015
• Actual Primary Completion Date: Oct 28, 2016
• Actual Study Completion Date: Jul 7, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 3-DAA with or without SOF and RBV 3-DAA (ombitasvir/paritaprevir/ritonavir once daily [QD] and dasabuvir twice daily [BID]) with and without sofosbuvir (SOF) QD and with or without ribavirin (RBV) BID for 12 or 24 weeks	Drug: ombitasvir/paritaprevir/ritonavir and dasabuvir; tablet, ombitasvir coformulated with paritaprevir and ritonavir; tablet, dasabuvir; 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: Sofosbuvir; tablet; Other Names: Sovaldi ; Drug: Ribavirin; tablet; Other Names: RBV

Outcome Measures

Primary Outcome Measures

1. Percentage of Part 1 Participants With Sustained Virologic Response 12 (SVR12) Weeks Posttreatment [12 weeks after the last dose of active 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 Part 2 Participants With Sustained Virologic Response 12 (SVR12) Weeks Post-treatment [12 weeks after the last dose of active drug]

   SVR12 was defined as plasma HCV RNA level <LLOQ 12 weeks after the last dose of study drug

2. Percentage of Participants With On-treatment Virologic Failure [Up to week 24]

   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 post-baseline HCV RNA during treatment, or HCV RNA ≥ LLOQ persistently during treatment with at least 6 weeks of treatment.

3. Percentage of Participants With Post-Treatment Relapse [Within 12 weeks after the last actual dose of active 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:

• History of previous direct acting antiviral (DAA) therapy failure; Part 2 only: history of previous direct acting antiviral (DAA) therapy failure and received at least 8 weeks of SOF/ledipasvir; participant must be treatment naïve to all other anti-HCV therapies

• HCV genotype 1 infection

• Females must be post-menopausal, of non-child bearing potential or practicing specific forms of birth control

Exclusion Criteria:

• Positive screen for hepatitis B surface antigen or anti-human immunodeficiency virus antibody

• Discontinuation of the prior DAA treatment for reasons other than virologic failure

• Confirmed presence of hepatocellular carcinoma

• Abnormal lab tests

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: NCT02356562
• Other Study ID Numbers: M14-224
• First Posted: Feb 5, 2015
• Last Update Posted: Dec 20, 2017
• Last Verified: Oct 1, 2017

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by AbbVie: Hepatitis C; Interferon-Free; Treatment Experienced; Chronic Hepatitis C; Hepatitis C Virus
• Additional relevant MeSH terms: Infections; Communicable Diseases; Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic; Ritonavir; Ribavirin; Sofosbuvir

Study Results

Participant Flow

Recruitment Details	Efficacy, safety, and demographic analyses were performed separately for the 2 study parts using the intent-to-treat (ITT) population, which consists of all enrolled participants who received at least one dose of study drug.
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	Part 1, 3-DAA With SOF With or Without RBV	Part 2, 3-DAA With 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]) and sofosbuvir (SOF) 400 mg QD with or without ribavirin (RBV; weight-based dosing 1000 or 1200 mg divided BID or renally adjusted for participants with creatinine clearance < 50 mL/min) for 12 or 24 weeks	3-DAA (ombitasvir/paritaprevir/ritonavir 25 mg/150 mg/100 mg QD and dasabuvir 250 mg BID) with RBV (weight-based dosing 1000 or 1200 mg divided BID or renally adjusted for participants with creatinine clearance < 50 mL/min) for 24 weeks
Period Title: Overall Study
STARTED	22	7
COMPLETED	20	6
NOT COMPLETED	2	1

Baseline Characteristics

Arm/Group Title	Part 1, 3-DAA With SOF With or Without RBV	Part 2, 3-DAA With RBV	Total
Arm/Group Description	3-DAA (ombitasvir/paritaprevir/ritonavir 25 mg/150 mg/100 mg once daily [QD] and dasabuvir 250 mg twice daily [BID]) and sofosbuvir (SOF) 400 mg QD with or without ribavirin (RBV; weight-based dosing 1000 or 1200 mg divided BID or renally adjusted for participants with creatinine clearance < 50 mL/min) for 12 or 24 weeks	3-DAA (ombitasvir/paritaprevir/ritonavir 25 mg/150 mg/100 mg QD and dasabuvir 250 mg BID) with RBV (weight-based dosing 1000 or 1200 mg divided BID or renally adjusted for participants with creatinine clearance < 50 mL/min) for 24 weeks	Total of all reporting groups
Overall Participants	22	7	29
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.0 (6.41)	65.3 (9.60)	NA (NA)
Sex: Female, Male (Count of Participants)
Female	7 31.8%	1 14.3%	8 27.6%
Male	15 68.2%	6 85.7%	21 72.4%

Outcome Measures

1. Primary Outcome

Title	Percentage of Part 1 Participants With Sustained Virologic Response 12 (SVR12) Weeks Posttreatment
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 dose of active drug

Outcome Measure Data

Analysis Population Description

All Part 1 participants who received at least 1 dose of study drug (ITT population). Per protocol, data from Parts 1 and 2 were not combined for analysis.

Arm/Group Title	Part 1, 3-DAA With SOF With or Without 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]) and sofosbuvir (SOF) 400 mg QD with or without ribavirin (RBV; weight-based dosing 1000 or 1200 mg divided BID or renally adjusted for participants with creatinine clearance < 50 mL/min) for 12 or 24 weeks
Measure Participants	22
Number (95% Confidence Interval) [percentage of participants]	95.5 434.1%

2. Secondary Outcome

Title	Percentage of Part 2 Participants With Sustained Virologic Response 12 (SVR12) Weeks Post-treatment
Description	SVR12 was defined as plasma HCV RNA level <LLOQ 12 weeks after the last dose of study drug
Time Frame	12 weeks after the last dose of active drug

Outcome Measure Data

Analysis Population Description

All Part 2 participants who received at least 1 dose of study drug (ITT population). Per protocol, data from Parts 1 and 2 were not combined for analysis.

Arm/Group Title	Part 2, 3-DAA With RBV
Arm/Group Description	3-DAA (ombitasvir/paritaprevir/ritonavir 25 mg/150 mg/100 mg QD and dasabuvir 250 mg BID) with RBV (weight-based dosing 1000 or 1200 mg divided BID or renally adjusted for participants with creatinine clearance < 50 mL/min) for 24 weeks
Measure Participants	7
Number (95% Confidence Interval) [percentage of participants]	85.7 389.5%

3. 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 post-baseline HCV RNA during treatment, or HCV RNA ≥ LLOQ persistently during treatment with at least 6 weeks of treatment.
Time Frame	Up to week 24

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug (ITT population). Per protocol, data from Parts 1 and 2 were not combined for analysis.

Arm/Group Title	Part 1, 3-DAA With SOF With or Without RBV	Part 2, 3-DAA With 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]) and sofosbuvir (SOF) 400 mg QD with or without ribavirin (RBV; weight-based dosing 1000 or 1200 mg divided BID or renally adjusted for participants with creatinine clearance < 50 mL/min) for 12 or 24 weeks	3-DAA (ombitasvir/paritaprevir/ritonavir 25 mg/150 mg/100 mg QD and dasabuvir 250 mg BID) with RBV (weight-based dosing 1000 or 1200 mg divided BID or renally adjusted for participants with creatinine clearance < 50 mL/min) for 24 weeks
Measure Participants	22	7
Number (95% Confidence Interval) [percentage of participants]	0.0 0%	14.3 204.3%

4. 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 actual dose of active study drug

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug (ITT population) with HCV RNA < LLOQ at the end of treatment and completed treatment. Per protocol, data from Parts 1 and 2 were not combined for analysis.

Arm/Group Title	Part 1, 3-DAA With SOF With or Without RBV	Part 2, 3-DAA With 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]) and sofosbuvir (SOF) 400 mg QD with or without ribavirin (RBV; weight-based dosing 1000 or 1200 mg divided BID or renally adjusted for participants with creatinine clearance < 50 mL/min) for 12 or 24 weeks	3-DAA (ombitasvir/paritaprevir/ritonavir 25 mg/150 mg/100 mg QD and dasabuvir 250 mg BID) with RBV (weight-based dosing 1000 or 1200 mg divided BID or renally adjusted for participants with creatinine clearance < 50 mL/min) for 24 weeks
Measure Participants	21	6
Number (95% Confidence Interval) [percentage of participants]	4.8 21.8%	0.0 0%

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 on or after the date of 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	Part 1, 3-DAA With SOF With or Without RBV		Part 2, 3-DAA With 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]) and sofosbuvir (SOF) 400 mg QD with or without ribavirin (RBV; weight-based dosing 1000 or 1200 mg divided BID or renally adjusted for participants with creatinine clearance < 50 mL/min) for 12 or 24 weeks.		3-DAA (ombitasvir/paritaprevir/ritonavir [25 mg/150 mg/100 mg QD and dasabuvir [250 mg BID) with RBV (weight-based dosing 1000 or 1200 mg divided BID or renally adjusted for participants with creatinine clearance < 50 mL/min) for 24 weeks.
All Cause Mortality
	Part 1, 3-DAA With SOF With or Without RBV		Part 2, 3-DAA With RBV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Part 1, 3-DAA With SOF With or Without RBV		Part 2, 3-DAA With RBV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/22 (9.1%)		0/7 (0%)
Infections and infestations
CELLULITIS	1/22 (4.5%)		0/7 (0%)
PNEUMONIA	1/22 (4.5%)		0/7 (0%)
Other (Not Including Serious) Adverse Events
	Part 1, 3-DAA With SOF With or Without RBV		Part 2, 3-DAA With RBV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/22 (90.9%)		6/7 (85.7%)
Blood and lymphatic system disorders
ANAEMIA	0/22 (0%)		1/7 (14.3%)
HAEMOLYTIC ANAEMIA	1/22 (4.5%)		0/7 (0%)
Cardiac disorders
VENTRICULAR EXTRASYSTOLES	1/22 (4.5%)		0/7 (0%)
Ear and labyrinth disorders
VERTIGO	1/22 (4.5%)		0/7 (0%)
VERTIGO POSITIONAL	1/22 (4.5%)		0/7 (0%)
Endocrine disorders
CUSHING'S SYNDROME	1/22 (4.5%)		0/7 (0%)
Gastrointestinal disorders
ABDOMINAL PAIN	1/22 (4.5%)		0/7 (0%)
DENTAL CARIES	1/22 (4.5%)		0/7 (0%)
DIARRHOEA	4/22 (18.2%)		1/7 (14.3%)
DRY MOUTH	1/22 (4.5%)		0/7 (0%)
GASTROOESOPHAGEAL REFLUX DISEASE	1/22 (4.5%)		1/7 (14.3%)
IMPAIRED GASTRIC EMPTYING	0/22 (0%)		1/7 (14.3%)
MOUTH ULCERATION	1/22 (4.5%)		0/7 (0%)
NAUSEA	3/22 (13.6%)		0/7 (0%)
ORAL PAIN	1/22 (4.5%)		0/7 (0%)
VOMITING	1/22 (4.5%)		0/7 (0%)
General disorders
ASTHENIA	2/22 (9.1%)		0/7 (0%)
CYST	1/22 (4.5%)		0/7 (0%)
ENERGY INCREASED	1/22 (4.5%)		0/7 (0%)
FATIGUE	7/22 (31.8%)		3/7 (42.9%)
FEELING COLD	1/22 (4.5%)		0/7 (0%)
MALAISE	0/22 (0%)		1/7 (14.3%)
OEDEMA PERIPHERAL	1/22 (4.5%)		0/7 (0%)
PYREXIA	2/22 (9.1%)		0/7 (0%)
Infections and infestations
CONJUNCTIVITIS BACTERIAL	0/22 (0%)		1/7 (14.3%)
EAR INFECTION	1/22 (4.5%)		0/7 (0%)
GASTROENTERITIS	2/22 (9.1%)		0/7 (0%)
INFLUENZA	1/22 (4.5%)		0/7 (0%)
SINUSITIS	1/22 (4.5%)		0/7 (0%)
STAPHYLOCOCCAL SKIN INFECTION	1/22 (4.5%)		0/7 (0%)
URINARY TRACT INFECTION	2/22 (9.1%)		0/7 (0%)
VIRAL UPPER RESPIRATORY TRACT INFECTION	1/22 (4.5%)		0/7 (0%)
Injury, poisoning and procedural complications
MUSCLE STRAIN	1/22 (4.5%)		1/7 (14.3%)
Investigations
ALANINE AMINOTRANSFERASE INCREASED	1/22 (4.5%)		1/7 (14.3%)
ASPARTATE AMINOTRANSFERASE INCREASED	0/22 (0%)		1/7 (14.3%)
CREATININE RENAL CLEARANCE DECREASED	1/22 (4.5%)		1/7 (14.3%)
Metabolism and nutrition disorders
GLUCOSE TOLERANCE IMPAIRED	0/22 (0%)		1/7 (14.3%)
HYPOKALAEMIA	1/22 (4.5%)		0/7 (0%)
INCREASED APPETITE	1/22 (4.5%)		0/7 (0%)
Musculoskeletal and connective tissue disorders
MUSCLE SPASMS	1/22 (4.5%)		0/7 (0%)
MUSCULOSKELETAL CHEST PAIN	0/22 (0%)		1/7 (14.3%)
OSTEOPENIA	1/22 (4.5%)		0/7 (0%)
Nervous system disorders
DIZZINESS	3/22 (13.6%)		0/7 (0%)
HEADACHE	8/22 (36.4%)		1/7 (14.3%)
NEUROPATHY PERIPHERAL	1/22 (4.5%)		0/7 (0%)
SYNCOPE	1/22 (4.5%)		0/7 (0%)
Psychiatric disorders
AGITATION	1/22 (4.5%)		0/7 (0%)
EUPHORIC MOOD	1/22 (4.5%)		0/7 (0%)
INSOMNIA	4/22 (18.2%)		0/7 (0%)
IRRITABILITY	2/22 (9.1%)		0/7 (0%)
Renal and urinary disorders
HYPERTONIC BLADDER	1/22 (4.5%)		0/7 (0%)
Reproductive system and breast disorders
MENOPAUSAL SYMPTOMS	1/22 (4.5%)		0/7 (0%)
PROSTATITIS	1/22 (4.5%)		0/7 (0%)
Respiratory, thoracic and mediastinal disorders
COUGH	2/22 (9.1%)		0/7 (0%)
DYSPNOEA EXERTIONAL	2/22 (9.1%)		0/7 (0%)
SINUS CONGESTION	1/22 (4.5%)		0/7 (0%)
Skin and subcutaneous tissue disorders
ECZEMA	0/22 (0%)		1/7 (14.3%)
ERYTHEMA	1/22 (4.5%)		0/7 (0%)
NIGHT SWEATS	1/22 (4.5%)		0/7 (0%)
PRURITUS	1/22 (4.5%)		0/7 (0%)
RASH	2/22 (9.1%)		0/7 (0%)
SKIN LESION	0/22 (0%)		1/7 (14.3%)
Vascular disorders
DEEP VEIN THROMBOSIS	1/22 (4.5%)		0/7 (0%)
FLUSHING	1/22 (4.5%)		0/7 (0%)

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.