A Study to Evaluate the Efficacy and Safety of Three Experimental Drugs in Adults With Hepatitis C Virus Infection, Who Are Either Treatment-naive or Treatment-experienced in Brazil

• Sponsor: AbbVie (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02442271
• Collaborator: (none)
• Enrollment: 222
• Arm: 1
• Actual Duration (Months): 17

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the proportion of subjects achieving sustained virologic response 12 weeks post-treatment (SVR12) in adults with genotype 1 (GT1) chronic HCV infection, who received treatment with 3 direct-acting antiviral agents (3-DAAs; ombitasvir/paritaprevir/ritonavir and dasabuvir) with or without ribavirin.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis C Infection	Drug: ombitasvir/paritaprevir/ritonavir and dasabuvir; Drug: ribavirin	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 222 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Multicenter Study to Evaluate the Efficacy and Safety of Ombitasvir/ABT-450/Ritonavir and Dasabuvir With or Without Ribavirin (RBV) in Treatment-Naïve or Treatment-Experienced Adults in Brazil With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection (TOPAZ III)
• Actual Study Start Date: Apr 27, 2015
• Actual Primary Completion Date: Jul 4, 2016
• Actual Study Completion Date: Sep 26, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 3-DAA ± RBV 3-DAA (ombitasvir/paritaprevir/ritonavir [25 mg/150 mg/100 mg once daily] and dasabuvir [250 mg twice daily]) with or without weight-based ribavirin (± RBV; dosed 1,000 or 1,200 mg daily divided twice a day) for 12 or 24 weeks.	Drug: ombitasvir/paritaprevir/ritonavir and dasabuvir; Tablet; ombitasvir coformulated with paritaprevir and ritonavir, dasabuvir tablet; Other Names: Viekira Pak paritaprevir also known as ABT-450 ombitasvir also known as ABT-267 dasabuvir also known as ABT-333 ; Drug: ribavirin; Tablet

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

1. Percentage of Participants With SVR12 by Fibrosis Stage [12 weeks after the last actual dose of study drug]

   SVR12 was defined as plasma HCV RNA level <LLOQ]12 weeks after the last dose of study drug. The percentage of participants achieving SVR12 by fibrosis stage (F3 and F4) are presented. Participants with missing data were counted as failures.

2. Percentage of Participants With SVR12 by Participant Prior HCV Treatment Experience [12 weeks after the last actual dose of study drug]

   SVR12 was defined as HCV RNA level <LLOQ 12 weeks after the last dose of study drug. Data are presented by prior HCV treatment experience. Data are provided by participants' prior HCV treatment experience at screening. Participants with missing data were counted as failures.

3. Percentage of Participants With SVR12 by Participant Eligibility for Treatment With Interferon (IFN) at Screening [12 weeks after the last actual dose of study drug]

   SVR12 was defined as HCV RNA level <LLOQ 12 weeks after the last dose of study drug. Data are presented by prior HCV treatment experience. Data are provided by participants' eligibility for treatment with IFN at screening. Participants with missing data were counted as failures.

4. Hepatitis C Virus Patient-Reported Outcomes Instrument (HCV-PRO) Total Score: Change From Baseline to 12 Weeks After the Last Dose of Study Drug [Day 1 (Baseline), 12 weeks after the last actual dose of the study drug]

   The HCV-PRO has been developed to capture the function and well-being impact of HCV conditions and treatment and contains 16 items important to HCV-infected patients; items were totaled to a summary score. Scores range from 0 to 100. A higher HCV-PRO score indicates a better state of health and a decrease from baseline represents worsening. If a participant answered at least 12 of the 16 items, the missing items were imputed with the mean score of the answered items; if a participant did not answer at least 12 of the items, the total score was considered missing.

5. Short-Form 36 Version 2 Health Survey (SF-36v2) Physical Component Summary (PCS) Scores: Change From Baseline to 12 Weeks After the Last Dose of Study Drug [Day 1 (Baseline), 12 weeks after the last actual dose of the study drug]

   The SF-36v2 is a non-disease specific Health Related Quality of Life (HRQoL) instrument. The SF-36v2 comprises 36 total items (questions) targeting a subject's functional health and well-being in 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health) with a recall period of four weeks. Domain scores are aggregated into a Physical Component Summary (PCS) score and a Mental Component Summary (MCS) score. SF-36v2 scores range from 1-100: higher scores indicate a better state of health and a decrease from baseline represents worsening. If a participant answered at least 50% of the items in a multi-item scale of the SF-36v2, the missing items were imputed with the average score of the answered items in the same domain. In cases where the participant did not answer at least 50% of the items, the score for that domain was considered missing. The SF-36v2 MCS and PCS scores were not computed if any domain

6. (SF-36v2) Mental Component Summary (MCS) Scores: Change From Baseline to 12 Weeks After the Last Dose of Study Drug [Day 1 (Baseline), 12 weeks after the last actual dose of the study drug]

   The SF-36v2 is a non-disease specific Health Related Quality of Life (HRQoL) instrument. The SF-36v2 comprises 36 total items (questions) targeting a subject's functional health and well-being in 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health) with a recall period of four weeks. Domain scores are aggregated into a PCS score and a MCS score. Scores SF-36v2 scores range from 1-100: higher scores indicate a better state of health and a decrease from baseline represents worsening. If a participant answered at least 50% of the items in a multi-item scale of the SF-36v2, the missing items were imputed with the average score of the answered items in the same domain. In cases where the participant did not answer at least 50% of the items, the score for that domain was considered missing. The SF-36v2 MCS and PCS scores were not computed if any domain was missing.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Females must be post-menopausal for more than 2 years or surgically sterile or practicing acceptable forms of birth control

• Males must be surgically sterile or agree to practice acceptable forms of birth control

• Chronic hepatitis C virus (HCV) infection at screening

• Fibrosis stage F3 or greater, documented by acceptable tests

• Participants with cirrhosis: Absence of hepatocellular carcinoma (HCC) as indicated by acceptable methods

Exclusion Criteria:

• Women who are pregnant or breastfeeding

• Positive test result for Hepatitis B surface antigen (HbsAg) or anti-HIV antibody positive (HIV Ab)

• Use of contraindicated medications within 2 weeks of dosing

• Clinically significant abnormalities or co-morbidities

• History of solid organ transplant

• Abnormal laboratory tests

• Current or past clinical evidence of Child-Pugh B or C classification or clinical history of liver decompensation

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• AbbVie

Investigators

• Study Director: AbbVie Inc, AbbVie

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT02442271
• Other Study ID Numbers: M14-225
• First Posted: May 13, 2015
• Last Update Posted: Aug 1, 2017
• Last Verified: Jul 1, 2017

• Keywords provided by AbbVie: Chronic Hepatitis C; Hepatitis C Treatment Naive; Hepatitis C Genotype 1; Hepatitis C Treatment Experienced; Hepatitis C Virus
• Additional relevant MeSH terms: Infections; Communicable Diseases; Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic; Ritonavir; Ribavirin

Study Results

Participant Flow

Pre-assignment Detail	Treatment regimen was assigned according to HCV genotype/subtype and cirrhosis status.

Arm/Group Title	3-DAA ± RBV
Arm/Group Description	3-DAA (ombitasvir/paritaprevir/ritonavir [25 mg/150 mg/100 once daily] and dasabuvir [250 mg twice daily]) with or without weight-based ribavirin (± RBV; dosed 1,000 or 1,200 mg daily divided twice a day) for 12 or 24 weeks.
Period Title: Overall Study
STARTED	222
COMPLETED	218
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	3-DAA ± RBV
Arm/Group Description	3-DAA (ombitasvir/paritaprevir/ritonavir [25 mg/150 mg/100 once daily] and dasabuvir [250 mg twice daily]) with or without weight-based ribavirin (± RBV; dosed 1,000 or 1,200 mg daily divided twice a day) for 12 or 24 weeks.
Overall Participants	222
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.6 (10.34)
Sex: Female, Male (Count of Participants)
Female	99 44.6%
Male	123 55.4%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12)
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. Participants with missing data were counted as failures.
Time Frame	12 weeks after the last actual dose of study drug

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: all 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 once daily] and dasabuvir [250 mg twice daily]) with or without weight-based ribavirin (± RBV; dosed 1,000 or 1,200 mg daily divided twice a day) for 12 or 24 weeks.
Measure Participants	222
Number (95% Confidence Interval) [percentage of participants]	96.4 43.4%

2. Secondary Outcome

Title	Percentage of Participants With SVR12 by Fibrosis Stage
Description	SVR12 was defined as plasma HCV RNA level <LLOQ]12 weeks after the last dose of study drug. The percentage of participants achieving SVR12 by fibrosis stage (F3 and F4) are presented. Participants with missing data were counted as failures.
Time Frame	12 weeks after the last actual dose of study drug

Outcome Measure Data

Analysis Population Description

All participants in the ITT population.

Arm/Group Title	Fibrosis Stage F3	Fibrosis Stage F4
Arm/Group Description	Participants with baseline fibrosis stage F3 (without cirrhosis).	Participants with baseline fibrosis stage F4 (with compensated cirrhosis).
Measure Participants	89	133
Number (95% Confidence Interval) [percentage of participants]	96.6 43.5%	96.2 NaN

3. Secondary Outcome

Title	Percentage of Participants With SVR12 by Participant Prior HCV Treatment Experience
Description	SVR12 was defined as HCV RNA level <LLOQ 12 weeks after the last dose of study drug. Data are presented by prior HCV treatment experience. Data are provided by participants' prior HCV treatment experience at screening. Participants with missing data were counted as failures.
Time Frame	12 weeks after the last actual dose of study drug

Outcome Measure Data

Analysis Population Description

All participants in the ITT population.

Arm/Group Title	Treatment-Naive	Pegylated Interferon (PegIFN)/RBV Null Responders	Pegylated Interferon (PegIFN)//RBV Partial Responders	Pegylated Interferon (PegIFN)/RBV Non-Responders	Pegylated Interferon (PegIFN)/RBV Relapser	Pegylated Interferon (PegIFN)/RBV Breakthrough	IFN Interolerant	Other
Arm/Group Description	Participants who had never received any antiviral treatment for HCV infection.	Participants who had received prior treatment with pegIFN-based therapy for HCV infection and failed to achieve a 1 log10 IU/mL reduction in HCV RNA by Week 4 or a 2 log10 IU/mL reduction in HCV RNA by Week 12 during a prior IFN/RBV or pegIFN/RBV treatment course	Participants who had received prior treatment with pegIFN-based therapy for HCV infection and achieved at least a 2 log10 IU/mL reduction in HCV RNA by Week 12 during a prior IFN/RBV or pegIFN/RBV treatment course but failed to achieve HCV RNA undetectable at the end of treatment	Participants who had received prior treatment with pegIFN-based therapy for HCV infection and failed to achieve a 1 log10 IU/mL reduction in HCV RNA by Week 4 or a 2 log10 IU/mL reduction in HCV RNA by Week 12 during a prior IFN/RBV or pegIFN/RBV treatment course.	Participants who had received prior treatment with pegIFN-based therapy for HCV infection who achieved HCV undetectable at end of a prior IFN/RBV or pegIFN/RBV treatment course but HCV RNA was detectable following cessation of therapy	Participants who had received prior treatment with pegIFN-based therapy for HCV infection and achieved at least one documented result of HCV RNA undetectable during a prior IFN/RBV or pegIFN/RBV treatment course	Participants who did not meet any of the other definitions of treatment failure and discontinued IFN/RBV or pegIFN/RBV therapy due to IFN intolerability	Participants who received IFN treatment, including IFN or pegIFN monotherapy, IFN/RBV, or pegIFN/RBV experienced subjects. Includes subjects who do not have adequate documentation of response.
Measure Participants	102	22	7	26	34	12	7	12
Number (95% Confidence Interval) [percentage of participants]	96.1 43.3%	95.5 NaN	100 NaN	100 NaN	97.1 NaN	100 NaN	85.7 NaN	91.7 NaN

4. Secondary Outcome

Title	Percentage of Participants With SVR12 by Participant Eligibility for Treatment With Interferon (IFN) at Screening
Description	SVR12 was defined as HCV RNA level <LLOQ 12 weeks after the last dose of study drug. Data are presented by prior HCV treatment experience. Data are provided by participants' eligibility for treatment with IFN at screening. Participants with missing data were counted as failures.
Time Frame	12 weeks after the last actual dose of study drug

Outcome Measure Data

Analysis Population Description

All participants in the ITT population.

Arm/Group Title	Interferon (IFN)-Ineligible, Treatment-Naive	Interferon (IFN)-Eligible, Treatment-Naive	Interferon (IFN)-Ineligible, Treatment-Experienced	Interferon (IFN)-Eligible, Treatment-Experienced
Arm/Group Description	Participants who had never received any antiviral treatment for HCV infection and were ineligible for treatment with IFN at screening.	Participants who had never received any antiviral treatment for HCV infection and were eligible for treatment with IFN at screening.	Participants who had received prior antiviral treatment for HCV infection and were ineligible for treatment with IFN at screening.	Participants who had received prior antiviral treatment for HCV infection and were eligible for treatment with IFN at screening.
Measure Participants	10	92	7	113
Number (95% Confidence Interval) [percentage of participants]	90.0 40.5%	96.7 NaN	85.7 NaN	97.3 NaN

5. Secondary Outcome

Title	Hepatitis C Virus Patient-Reported Outcomes Instrument (HCV-PRO) Total Score: Change From Baseline to 12 Weeks After the Last Dose of Study Drug
Description	The HCV-PRO has been developed to capture the function and well-being impact of HCV conditions and treatment and contains 16 items important to HCV-infected patients; items were totaled to a summary score. Scores range from 0 to 100. A higher HCV-PRO score indicates a better state of health and a decrease from baseline represents worsening. If a participant answered at least 12 of the 16 items, the missing items were imputed with the mean score of the answered items; if a participant did not answer at least 12 of the items, the total score was considered missing.
Time Frame	Day 1 (Baseline), 12 weeks after the last actual dose of the study drug

Outcome Measure Data

Analysis Population Description

All participants in the ITT population with evaluable data.

Arm/Group Title	Fibrosis Stage F3	Fibrosis Stage F4
Arm/Group Description	Participants with baseline fibrosis stage F3 (without cirrhosis).	Participants with baseline fibrosis stage F4 (with compensated cirrhosis).
Measure Participants	88	130
SVR12 Not Achieved	0.5 (10.97)	0.8 (10.64)
SVR12 Achieved	3.8 (13.25)	4.2 (15.72)

6. Secondary Outcome

Title	Short-Form 36 Version 2 Health Survey (SF-36v2) Physical Component Summary (PCS) Scores: Change From Baseline to 12 Weeks After the Last Dose of Study Drug
Description	The SF-36v2 is a non-disease specific Health Related Quality of Life (HRQoL) instrument. The SF-36v2 comprises 36 total items (questions) targeting a subject's functional health and well-being in 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health) with a recall period of four weeks. Domain scores are aggregated into a Physical Component Summary (PCS) score and a Mental Component Summary (MCS) score. SF-36v2 scores range from 1-100: higher scores indicate a better state of health and a decrease from baseline represents worsening. If a participant answered at least 50% of the items in a multi-item scale of the SF-36v2, the missing items were imputed with the average score of the answered items in the same domain. In cases where the participant did not answer at least 50% of the items, the score for that domain was considered missing. The SF-36v2 MCS and PCS scores were not computed if any domain
Time Frame	Day 1 (Baseline), 12 weeks after the last actual dose of the study drug

Outcome Measure Data

Analysis Population Description

All participants in the ITT population with evaluable data.

Arm/Group Title	Fibrosis Stage F3	Fibrosis Stage F4
Arm/Group Description	Participants with baseline fibrosis stage F3 (without cirrhosis).	Participants with baseline fibrosis stage F4 (with compensated cirrhosis).
Measure Participants	87	131
SVR12 Not Achieved	-0.5 (9.22)	1.3 (8.59)
SVR12 Achieved	0.1 (6.42)	2.1 (7.60)

7. Secondary Outcome

Title	(SF-36v2) Mental Component Summary (MCS) Scores: Change From Baseline to 12 Weeks After the Last Dose of Study Drug
Description	The SF-36v2 is a non-disease specific Health Related Quality of Life (HRQoL) instrument. The SF-36v2 comprises 36 total items (questions) targeting a subject's functional health and well-being in 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health) with a recall period of four weeks. Domain scores are aggregated into a PCS score and a MCS score. Scores SF-36v2 scores range from 1-100: higher scores indicate a better state of health and a decrease from baseline represents worsening. If a participant answered at least 50% of the items in a multi-item scale of the SF-36v2, the missing items were imputed with the average score of the answered items in the same domain. In cases where the participant did not answer at least 50% of the items, the score for that domain was considered missing. The SF-36v2 MCS and PCS scores were not computed if any domain was missing.
Time Frame	Day 1 (Baseline), 12 weeks after the last actual dose of the study drug

Outcome Measure Data

Analysis Population Description

All participants in the ITT population with evaluable data.

Arm/Group Title	Fibrosis Stage F3	Fibrosis Stage F4
Arm/Group Description	Participants with baseline fibrosis stage F3 (without cirrhosis).	Participants with baseline fibrosis stage F4 (with compensated cirrhosis).
Measure Participants	87	131
SVR12 Not Achieved	2.4 (3.72)	-0.6 (8.47)
SVR12 Achieved	2.4 (11.39)	2.5 (9.15)

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 28 weeks).
Adverse Event Reporting Description	TEAEs and TESAEs are defined as any AE or SAE with onset or worsening after the first dose of study drug until 30 days after the last dose of study drug.
Arm/Group Title	3-DAA ± RBV
Arm/Group Description	3-DAA (ombitasvir/paritaprevir/ritonavir [25 mg/150 mg/100 once daily] and dasabuvir [250 mg twice daily]) with or without weight-based ribavirin (± RBV; dosed 1,000 or 1,200 mg daily 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	6/222 (2.7%)
Gastrointestinal disorders
DIARRHOEA	1/222 (0.5%)
OESOPHAGEAL VARICES HAEMORRHAGE	1/222 (0.5%)
Hepatobiliary disorders
HEPATIC FAILURE	1/222 (0.5%)
Infections and infestations
GASTROENTERITIS	1/222 (0.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
LUNG ADENOCARCINOMA METASTATIC	1/222 (0.5%)
Nervous system disorders
TRANSIENT ISCHAEMIC ATTACK	1/222 (0.5%)
Renal and urinary disorders
RENAL FAILURE	1/222 (0.5%)
Other (Not Including Serious) Adverse Events
	3-DAA ± RBV
	Affected / at Risk (%)	# Events
Total	139/222 (62.6%)
Blood and lymphatic system disorders
ANAEMIA	16/222 (7.2%)
Gastrointestinal disorders
DIARRHOEA	19/222 (8.6%)
DYSPEPSIA	15/222 (6.8%)
NAUSEA	34/222 (15.3%)
General disorders
ASTHENIA	20/222 (9%)
FATIGUE	41/222 (18.5%)
Nervous system disorders
HEADACHE	48/222 (21.6%)
Psychiatric disorders
INSOMNIA	12/222 (5.4%)
Respiratory, thoracic and mediastinal disorders
COUGH	14/222 (6.3%)
Skin and subcutaneous tissue disorders
PRURITUS	32/222 (14.4%)

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.