Turquoise-IV: A Study to Evaluate Chronic Hepatitis C Virus (HCV) Infection in Cirrhotic Adults With Genotype 1b (GT1b) Infection

• Sponsor: AbbVie (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02216422
• Collaborator: (none)
• Enrollment: 36
• Arm: 1
• Duration (Months): 15

Study Details

Study Description

Brief Summary

This was a multicenter study evaluating the efficacy and safety of ombitasvir/paritaprevir/ritonavir and dasabuvir co-administered with ribavirin (RBV) for 12 weeks in treatment naïve and pegylated-interferon alfa-2a or alfa-2b (pegIFN)/RBV treatment-experienced, cirrhotic HCV genotype 1b-infected adults.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis C Virus (HCV) Infection	Drug: Ombitasvir/Paritaprevir/Ritonavir; Drug: Dasabuvir; Drug: Ribavirin (RBV)	Phase 3

Detailed Description

The primary objective of this study was to assess the safety and efficacy (the percentage of participants achieving a 12-week sustained virologic response (SVR12), [HCV ribonucleic acid (RNA) < lower limit of quantification (LLOQ) 12 weeks following treatment]) of co-formulated ombitasvir, paritaprevir, and ritonavir (ombitasvir/paritaprevir/r) and dasabuvir co-administered with RBV for 12 weeks in HCV genotype 1b-infected adult participants with compensated cirrhosis. The secondary objectives of this study were to assess the number and percentage of participants with virologic failure during treatment and the percentage of participants with relapse post-treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Single-Arm Study to Evaluate the Safety and Efficacy of ABT-450/Ritonavir/ABT-267 (ABT-450/r/ABT-267) and ABT-333 Co-administered With Ribavirin (RBV) in Adults With Genotype 1b Chronic Hepatitis C Virus (HCV) Infection and Cirrhosis (Turquoise-IV)
• Study Start Date: Sep 1, 2014
• Actual Primary Completion Date: Dec 1, 2015
• Actual Study Completion Date: Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ombitasvir/Paritaprevir/Ritonavir plus Dasabuvir with RBV Ombitasvir/Paritaprevir/Ritonavir (25/150/100 mg once daily) and Dasabuvir (250 mg twice daily) co-administered with weight-based Ribavirin (RBV; twice daily) for 12 weeks	Drug: Ombitasvir/Paritaprevir/Ritonavir; Tablet; paritaprevir co-formulated with ritonavir and ombitasvir; Other Names: ABT-267 also known as ombitasvir ABT-450 also known as paritaprevir Ritonavir also known as norvir ; Drug: Dasabuvir; Tablet; Other Names: ABT-333 ; Drug: Ribavirin (RBV); Tablet

Outcome Measures

Primary Outcome Measures

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

   Sustained Virologic Response 12 (SVR12) is defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) less than the lower limit of quantification (< LLOQ; < 25 IU/mL) 12 weeks after the last dose of study drug. Participants with missing data were imputed as failures.

Secondary Outcome Measures

1. Percentage of Participants With On-Treatment Virologic Failure [Day 1 through Week 12]

   On-Treatment Virologic Failure is defined as confirmed HCV RNA >= LLOQ after HCV RNA < LLOQ during treatment, or confirmed increase from nadir (local minimum value) in HCV RNA [2 consecutive HCV RNA measurements > 1 log10 IU/mL above nadir] at any time point during treatment, or failure to suppress during treatment [all on-treatment values of HCV RNA >= LLOQ] with at least 6 weeks [defined as active study drug duration ≥ 36 days] of treatment.

2. Percentage of Participants With Post-Treatment Relapse [Post-treatment Day 1 to Post-treatment Week 12]

   Post- Treatment Relapse is defined as confirmed HCV RNA >= LLOQ between end of treatment and 12 weeks after last actual dose of active study drug [up to and including the SVR12 assessment time point] for a participant with HCV RNA < LLOQ at Final Treatment Visit who completes treatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Chronic hepatitis C, genotype 1b-infection (HCV RNA level greater than 1,000 IU/mL at Screening)

• Evidence of liver cirrhosis as confirmed by liver biopsy or Fibroscan with Child-Pugh score less than or equal to 6 at Screening

• Participant had never received antiviral treatment (including pegIFN/RBV) for hepatitis C infection (treatment-naïve participant) or had documentation of meeting one of the defined categories of a treatment-experienced participants

• Absence of hepatocellular carcinoma (HCC) as indicated by a negative ultrasound, computed tomography (CT) scan, or magnetic resonance imaging (MRI) performed within 3 months prior to screening or a negative ultrasound at screening.

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

• Males must have been surgically sterile, or agreed to practice 2 effective methods of birth control throughout the course of the study.

Exclusion Criteria:

• Positive screen for hepatitis B Surface antigen or anti-Human Immunodeficiency virus antibody

• Evidence of current or past Child-Pugh B or C classification

• Confirmed presence of hepatocellular carcinoma

• Abnormal laboratory tests

• Participant who self-reported on average drinking more than 2 drinks per day for current drinkers

• Previous treatment with a direct acting antiviral agent (DAA) containing regimen

• History of solid organ transplant.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• AbbVie

Investigators

• Study Director: Rolando M Viani, MD, AbbVie

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT02216422
• Other Study ID Numbers: M14-252
• First Posted: Aug 15, 2014
• Last Update Posted: Jun 29, 2016
• Last Verified: May 1, 2016

• Keywords provided by AbbVie: Chronic Hepatitis C; Hepatitis C; Hepatitis C Virus; Hepatitis C Genotype 1b; Interferon-Free
• Additional relevant MeSH terms: Infections; Communicable Diseases; Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic; Ritonavir; Ribavirin

Study Results

Participant Flow

Recruitment Details	A total of 36 participants were enrolled and all the participants completed the study. All 36 participants were analyzed for both efficacy (included all participants who received at least 1 dose of study drug (ITT)) and safety.

Arm/Group Title	Ombitasvir/Paritaprevir/Ritonavir Plus Dasabuvir With RBV
Arm/Group Description	Ombitasvir/Paritaprevir/Ritonavir (25/150/100 mg once daily) and Dasabuvir (250 mg twice daily) co-administered with weight-based Ribavirin (RBV; twice daily) for 12 weeks.
Period Title: Overall Study
STARTED	36
COMPLETED	36
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Ombitasvir/Paritaprevir/Ritonavir Plus Dasabuvir With RBV
Arm/Group Description	Ombitasvir/Paritaprevir/Ritonavir (25/150/100 mg once daily) and Dasabuvir (250 mg twice daily) co-administered with weight-based Ribavirin (RBV; twice daily) for 12 weeks.
Overall Participants	36
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.6 (7.91)
Sex: Female, Male (Count of Participants)
Female	13 36.1%
Male	23 63.9%
Interleukin 28B (IL28B) (participants) [Number]
CC	4 11.1%
CT	25 69.4%
TT	7 19.4%
Missing	0 0%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Sustained Virologic Response 12 Weeks (SVR12) Post-treatment
Description	Sustained Virologic Response 12 (SVR12) is defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) less than the lower limit of quantification (< LLOQ; < 25 IU/mL) 12 weeks after the last dose of study drug. Participants with missing data were imputed as failures.
Time Frame	Post-treatment Day 1 to Post-treatment Week 12

Outcome Measure Data

Analysis Population Description

Efficacy analyses included all participants who received at least 1 dose of study drug (ITT).

Arm/Group Title	Ombitasvir/Paritaprevir/Ritonavir Plus Dasabuvir With RBV
Arm/Group Description	Ombitasvir/Paritaprevir/Ritonavir (25/150/100 mg once daily) and Dasabuvir (250 mg twice daily) co-administered with weight-based Ribavirin (RBV; twice daily) for 12 weeks.
Measure Participants	36
Number (95% Confidence Interval) [percentage of participants]	100 277.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ombitasvir/Paritaprevir/Ritonavir Plus Dasabuvir With RBV
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of Participants
	Estimated Value	100
	Confidence Interval	(2-Sided) 95%; 90.4 to 100.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% confidence interval (CI) was calculated using Wilson score method.

2. Secondary Outcome

Title	Percentage of Participants With On-Treatment Virologic Failure
Description	On-Treatment Virologic Failure is defined as confirmed HCV RNA >= LLOQ after HCV RNA < LLOQ during treatment, or confirmed increase from nadir (local minimum value) in HCV RNA [2 consecutive HCV RNA measurements > 1 log10 IU/mL above nadir] at any time point during treatment, or failure to suppress during treatment [all on-treatment values of HCV RNA >= LLOQ] with at least 6 weeks [defined as active study drug duration ≥ 36 days] of treatment.
Time Frame	Day 1 through Week 12

Outcome Measure Data

Analysis Population Description

Efficacy analyses included all participants who received at least 1 dose of study drug (ITT).

Arm/Group Title	Ombitasvir/Paritaprevir/Ritonavir Plus Dasabuvir With RBV
Arm/Group Description	Ombitasvir/Paritaprevir/Ritonavir (25/150/100 mg once daily) and Dasabuvir (250 mg twice daily) co-administered with weight-based Ribavirin (RBV; twice daily) for 12 weeks.
Measure Participants	36
Number (95% Confidence Interval) [percentage of participants]	0 0%

3. Secondary Outcome

Title	Percentage of Participants With Post-Treatment Relapse
Description	Post- Treatment Relapse is defined as confirmed HCV RNA >= LLOQ between end of treatment and 12 weeks after last actual dose of active study drug [up to and including the SVR12 assessment time point] for a participant with HCV RNA < LLOQ at Final Treatment Visit who completes treatment.
Time Frame	Post-treatment Day 1 to Post-treatment Week 12

Outcome Measure Data

Analysis Population Description

Efficacy analyses included all participants who received at least 1 dose of study drug (ITT).

Arm/Group Title	Ombitasvir/Paritaprevir/Ritonavir Plus Dasabuvir With RBV
Arm/Group Description	Ombitasvir/Paritaprevir/Ritonavir (25/150/100 mg once daily) and Dasabuvir (250 mg twice daily) co-administered with weight-based Ribavirin (RBV; twice daily) for 12 weeks.
Measure Participants	36
Number (95% Confidence Interval) [percentage of participants]	0 0%

Adverse Events

Time Frame	AEs and SAEs were collected from the time of study drug administration to 30 days after last dose of study drug (12 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (up to 36 weeks).
Arm/Group Title	Ombitasvir/Paritaprevir/Ritonavir Plus
Arm/Group Description	Ombitasvir/Paritaprevir/Ritonavir (25/150/100 mg once daily) and Dasabuvir (250 mg twice daily) co-administered with weight-based Ribavirin (RBV; twice daily) for 12 weeks.
All Cause Mortality
	Ombitasvir/Paritaprevir/Ritonavir Plus
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Ombitasvir/Paritaprevir/Ritonavir Plus
	Affected / at Risk (%)	# Events
Total	0/36 (0%)
Other (Not Including Serious) Adverse Events
	Ombitasvir/Paritaprevir/Ritonavir Plus
	Affected / at Risk (%)	# Events
Total	21/36 (58.3%)
Blood and lymphatic system disorders
ANAEMIA	8/36 (22.2%)
LEUKOPENIA	2/36 (5.6%)
Gastrointestinal disorders
ABDOMINAL PAIN UPPER	2/36 (5.6%)
NAUSEA	2/36 (5.6%)
General disorders
ASTHENIA	8/36 (22.2%)
FATIGUE	2/36 (5.6%)
Hepatobiliary disorders
HYPERBILIRUBINAEMIA	3/36 (8.3%)
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION	2/36 (5.6%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA	2/36 (5.6%)
Nervous system disorders
HEADACHE	4/36 (11.1%)
Psychiatric disorders
INSOMNIA	2/36 (5.6%)
Respiratory, thoracic and mediastinal disorders
COUGH	5/36 (13.9%)
DYSPNOEA EXERTIONAL	2/36 (5.6%)
Skin and subcutaneous tissue disorders
PRURITUS	2/36 (5.6%)

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.