Real World Evidence of the Effectiveness of Paritaprevir/r - Ombitasvir, ± Dasabuvir, ± Ribavirin in Participants With Chronic Hepatitis C

• Sponsor: AbbVie (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02725866
• Collaborator: (none)
• Enrollment: 216
• Duration (Months): 18.9

Study Details

Study Description

Brief Summary

The interferon-free combination regimen of paritaprevir/ritonavir/ombitasvir with or without dasabuvir (ABBVIE REGIMEN) ± ribavirin (RBV) for the treatment of chronic hepatitis C (CHC) has been shown to be safe and effective in randomized controlled clinical trials with strict inclusion and exclusion criteria under well-controlled conditions.

This observational study is the first effectiveness research examining the ABBVIE REGIMEN ± RBV, used according to the local label, under real-world conditions in Greece in a clinical practice patient population.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis C	Drug: Paritaprevir/ritonavir/ombitasvir; Drug: Dasabuvir; Drug: Ribavirin

Detailed Description

This was a prospective, multi-center observational study in participants receiving the interferon-free ABBVIE REGIMEN ± RBV. The prescription of a treatment regimen was at the discretion of the physician in accordance with local clinical practice and label, was made independently from this observational study and preceded the decision to offer the participant the opportunity to participate in this study. Adults chronically infected with hepatitis C virus (HCV), receiving the interferon-free ABBVIE REGIMEN, were offered the opportunity to participate in this study during a routine clinical visit at the participating sites. Follow-up visits, treatment, procedures, and diagnostic methods followed physicians' routine clinical practice. Data were collected at the following time windows: baseline, early on-treatment visit, mid-treatment visit (for participants with treatment duration of 24 weeks), end of treatment (EoT), early post-treatment and 12 and 24 weeks after the end of treatment (representing sustained virologic response 12 weeks after the end of treatment [SVR12] and sustained virologic response 24 weeks after the end of treatment [SVR24]).

Study Design

• Study Type: Observational
• Actual Enrollment: 216 participants
• Observational Model: Case-Only
• Time Perspective: Prospective
• Official Title: Real World Evidence of the Effectiveness of Paritaprevir/r - Ombitasvir, ± Dasabuvir, ± Ribavirin in Participants With Chronic Hepatitis C - An Observational Study in Greece
• Study Start Date: Apr 5, 2016
• Actual Primary Completion Date: Oct 31, 2017
• Actual Study Completion Date: Oct 31, 2017

Arms and Interventions

Arm	Intervention/Treatment
Participants with HCV genotype 1 or 4 Ombitasvir/paritaprevir/ritonavir (two 12.5 mg/75 mg/50 mg co-formulated tablets once daily); ± dasabuvir (tablet; 250 mg twice daily); ± weight-based ribavirin (tablet; 1000 or 1200 mg divided twice a day) up to 24 weeks	Drug: Paritaprevir/ritonavir/ombitasvir; Co-formulated tablet; Other Names: Paritaprevir also known as ABT-450 Ombitasvir also known as ABT-267 ; Drug: Dasabuvir; Tablet; Other Names: ABT-333 ; Drug: Ribavirin; Tablet

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Achieving 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 50 IU/mL 12 weeks after the last actual dose of study drug. The core population (CP) consisted of participants who met all inclusion criteria and were adequately treated according to the standard of care and within local label recommendations for their specific disease characteristics (cirrhotic status, genotype). The core population with sufficient follow-up data 12 weeks after the last actual dose of study drug (CPSFU12) was defined as all CP participants who fulfilled one of the following criteria: evaluable HCV RNA data ≥70 days after the last actual dose of the ABBVIE REGIMEN an HCV RNA value ≥50 IU/mL at the last measurement post-baseline HCV RNA <50 IU/mL at the last measurement post-baseline, but no HCV RNA measurement ≥70 days after the last actual dose of the ABBVIE REGIMEN due to reasons related to safety (e.g. dropped out due to AE) or virologic failure

Secondary Outcome Measures

1. Percentage of Participants With Virologic Response at End of Treatment (EoT) [Up to 24 weeks]

   Virologic response was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than 50 IU/mL at the end of treatment.

2. Percentage of Participants With Relapse [Up to 24 weeks]

   Relapse was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than 50 IU/mL at the end of treatment followed by HCV RNA level greater than or equal to 50 IU/mL.

3. Percentage of Participants With Viral Breakthrough [Up to 24 weeks]

   Viral breakthrough was defined as at least 1 documented plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than 50 IU/mL followed by HCV RNA level greater than or equal to 50 IU/mL during treatment.

4. Percentage of Participants With On-treatment Virologic Failure [12 weeks after the last actual dose of study drug]

   On-treatment virologic failure was defined as breakthrough (at least 1 documented plasma hepatitis C virus ribonucleic acid (HCV RNA) less than 50 IU/mL followed by HCV RNA greater than or equal to 50 IU/mL during treatment) or failure to suppress (each measured on-treatment HCV RNA value greater than or equal to 50 IU/mL).

5. Percentage of Participants Meeting Relapse Criteria [12 weeks after the last actual dose of study drug]

   Relapse was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) less than 50 IU/mL at end of treatment or at the last on-treatment HCV RNA measurement followed by HCV RNA greater than or equal to 50 IU/mL post-treatment.

6. Percentage of Participants Meeting Premature Study Drug Discontinuation Criteria [12 weeks after the last actual dose of study drug]

   Premature study drug discontinuation was defined as participants who prematurely discontinued study drug with no on-treatment virologic failure.

7. Percentage of Participants With Missing Sustained Virologic Response 12 Weeks Post-Treatment (SVR12) Data and/or Nonresponders Who Did Not Meet Specific SVR12 Nonresponder Criteria [12 weeks after the last actual dose of study drug]

   The number of participants with missing SVR12 data or SVR12 nonresponder participants who did not meet criteria for on-treatment virologic failure, relapse, premature treatment discontinuation, and who did not have an Insufficient virological response was documented.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Treatment-naïve or -experienced adult male or female participants with confirmed chronic hepatitis C (CHC), genotype 1 or 4, receiving combination therapy with the interferon-free ABBVIE REGIMEN ± ribavirin (RBV) according to standard of care and in line with the current local label

• If RBV was co-administered with the ABBVIE REGIMEN, it had to be prescribed in line with the current local label (with special attention to contraception requirements and contraindication during pregnancy)

• Participants had to voluntarily sign and date an informed consent form prior to inclusion into the study

• Participant must not have participated or intended to participate in a concurrent interventional therapeutic trial

Exclusion Criteria:

• None

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• AbbVie

Investigators

• Study Chair: Georgios Mitas, MS, AbbVie Pharmaceuticals S.A. (Greece)

Study Documents (Full-Text)

• Study Protocol - Jan 18, 2016
• Statistical Analysis Plan - Jul 28, 2017

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT02725866
• Other Study ID Numbers: P15-842
• First Posted: Apr 1, 2016
• Last Update Posted: Mar 15, 2019
• Last Verified: Oct 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by AbbVie: Observational Study; Sustained Virological Response; Chronic Hepatitis C genotype 1; Chronic Hepatitis C; Ombitasvir/paritaprevir/ritonavir ± dasabuvir; Chronic Hepatitis C genotype 4
• Additional relevant MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic; Ritonavir; Ribavirin

Study Results

Participant Flow

Pre-assignment Detail	Safety population: all enrolled participants who received at least one dose of the ABBVIE REGIMEN. The prescribed ABBVIE REGIMEN needed to be known.

Arm/Group Title	Participants With HCV Genotype 1 or 4
Arm/Group Description	Ombitasvir/paritaprevir/ritonavir (two 12.5 mg/75 mg/50 mg co-formulated tablets once daily); ± dasabuvir (tablet; 250 mg twice daily); ± weight-based ribavirin (tablet; 1000 or 1200 mg divided twice a day) up to 24 weeks
Period Title: Overall Study
STARTED	216
COMPLETED	202
NOT COMPLETED	14

Baseline Characteristics

Arm/Group Title	Participants With HCV Genotype 1 or 4
Arm/Group Description	Ombitasvir/paritaprevir/ritonavir (two 12.5 mg/75 mg/50 mg co-formulated tablets once daily); ± dasabuvir (tablet; 250 mg twice daily); ± weight-based ribavirin (tablet; 1000 or 1200 mg divided twice a day) up to 24 weeks
Overall Participants	216
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56 (13)
Sex: Female, Male (Count of Participants)
Female	101 46.8%
Male	115 53.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 0.5%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 0.9%
White	211 97.7%
More than one race	0 0%
Unknown or Not Reported	2 0.9%
Hepatitis C genotype (Count of Participants)
Genotype 1	151 69.9%
Genotype 4	65 30.1%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Achieving Sustained Virologic Response 12 Weeks Post-treatment (SVR12)
Description	SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than 50 IU/mL 12 weeks after the last actual dose of study drug. The core population (CP) consisted of participants who met all inclusion criteria and were adequately treated according to the standard of care and within local label recommendations for their specific disease characteristics (cirrhotic status, genotype). The core population with sufficient follow-up data 12 weeks after the last actual dose of study drug (CPSFU12) was defined as all CP participants who fulfilled one of the following criteria: evaluable HCV RNA data ≥70 days after the last actual dose of the ABBVIE REGIMEN an HCV RNA value ≥50 IU/mL at the last measurement post-baseline HCV RNA <50 IU/mL at the last measurement post-baseline, but no HCV RNA measurement ≥70 days after the last actual dose of the ABBVIE REGIMEN due to reasons related to safety (e.g. dropped out due to AE) or virologic failure
Time Frame	12 weeks after the last actual dose of study drug

Outcome Measure Data

Analysis Population Description

Core population (CP) and core population with sufficient follow-up data 12 weeks after the last actual dose of study drug (CPSFU12) are defined in the outcome measure description.

Arm/Group Title	Participants With HCV Genotype 1 or 4
Arm/Group Description	Ombitasvir/paritaprevir/ritonavir (two 12.5 mg/75 mg/50 mg co-formulated tablets once daily); ± dasabuvir (tablet; 250 mg twice daily); ± weight-based ribavirin (tablet; 1000 or 1200 mg divided twice a day) up to 24 weeks
Measure Participants	213
Core population (CP)	91.1 42.2%
CPSFU12	95.6 44.3%

2. Secondary Outcome

Title	Percentage of Participants With Virologic Response at End of Treatment (EoT)
Description	Virologic response was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than 50 IU/mL at the end of treatment.
Time Frame	Up to 24 weeks

Outcome Measure Data

Analysis Population Description

Core population: Participants meeting all inclusion criteria and who were adequately treated according to the standard of care and within local label recommendations for their specific disease characteristics (cirrhotic status, genotype).

Arm/Group Title	Participants With HCV Genotype 1 or 4
Arm/Group Description	Ombitasvir/paritaprevir/ritonavir (two 12.5 mg/75 mg/50 mg co-formulated tablets once daily); ± dasabuvir (tablet; 250 mg twice daily); ± weight-based ribavirin (tablet; 1000 or 1200 mg divided twice a day) up to 24 weeks
Measure Participants	213
Number (95% Confidence Interval) [percentage of participants]	93.9 43.5%

3. Secondary Outcome

Title	Percentage of Participants With Relapse
Description	Relapse was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than 50 IU/mL at the end of treatment followed by HCV RNA level greater than or equal to 50 IU/mL.
Time Frame	Up to 24 weeks

Outcome Measure Data

Analysis Population Description

Core population: Participants meeting all inclusion criteria and who were adequately treated according to the standard of care and within local label recommendations for their specific disease characteristics (cirrhotic status, genotype).

Arm/Group Title	Participants With HCV Genotype 1 or 4
Arm/Group Description	Ombitasvir/paritaprevir/ritonavir (two 12.5 mg/75 mg/50 mg co-formulated tablets once daily); ± dasabuvir (tablet; 250 mg twice daily); ± weight-based ribavirin (tablet; 1000 or 1200 mg divided twice a day) up to 24 weeks
Measure Participants	213
Number [percentage of participants]	0.9 0.4%

4. Secondary Outcome

Title	Percentage of Participants With Viral Breakthrough
Description	Viral breakthrough was defined as at least 1 documented plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than 50 IU/mL followed by HCV RNA level greater than or equal to 50 IU/mL during treatment.
Time Frame	Up to 24 weeks

Outcome Measure Data

Analysis Population Description

Core population (those meeting inclusion criteria and treated according to the standard of care and w/in local label guidelines for specific disease characteristics [cirrhotic status, genotype]) who had at least 1 undetectable or unquantifiable, on-treatment HCV RNA measurement and at least 1 on-treatment or end of treatment measurement thereafter.

Arm/Group Title	Participants With HCV Genotype 1 or 4
Arm/Group Description	Ombitasvir/paritaprevir/ritonavir (two 12.5 mg/75 mg/50 mg co-formulated tablets once daily); ± dasabuvir (tablet; 250 mg twice daily); ± weight-based ribavirin (tablet; 1000 or 1200 mg divided twice a day) up to 24 weeks
Measure Participants	213
Number (95% Confidence Interval) [percentage of participants]	0.0 0%

5. Secondary Outcome

Title	Percentage of Participants With On-treatment Virologic Failure
Description	On-treatment virologic failure was defined as breakthrough (at least 1 documented plasma hepatitis C virus ribonucleic acid (HCV RNA) less than 50 IU/mL followed by HCV RNA greater than or equal to 50 IU/mL during treatment) or failure to suppress (each measured on-treatment HCV RNA value greater than or equal to 50 IU/mL).
Time Frame	12 weeks after the last actual dose of study drug

Outcome Measure Data

Analysis Population Description

Core population: Participants meeting all inclusion criteria and who were adequately treated according to the standard of care and within local label recommendations for their specific disease characteristics (cirrhotic status, genotype).

Arm/Group Title	Participants With HCV Genotype 1 or 4
Arm/Group Description	Ombitasvir/paritaprevir/ritonavir (two 12.5 mg/75 mg/50 mg co-formulated tablets once daily); ± dasabuvir (tablet; 250 mg twice daily); ± weight-based ribavirin (tablet; 1000 or 1200 mg divided twice a day) up to 24 weeks
Measure Participants	213
Number [percentage of participants]	0.5 0.2%

6. Secondary Outcome

Title	Percentage of Participants Meeting Relapse Criteria
Description	Relapse was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) less than 50 IU/mL at end of treatment or at the last on-treatment HCV RNA measurement followed by HCV RNA greater than or equal to 50 IU/mL post-treatment.
Time Frame	12 weeks after the last actual dose of study drug

Outcome Measure Data

Analysis Population Description

Core population: Participants meeting all inclusion criteria and who were adequately treated according to the standard of care and within local label recommendations for their specific disease characteristics (cirrhotic status, genotype).

Arm/Group Title	Participants With HCV Genotype 1 or 4
Arm/Group Description	Ombitasvir/paritaprevir/ritonavir (two 12.5 mg/75 mg/50 mg co-formulated tablets once daily); ± dasabuvir (tablet; 250 mg twice daily); ± weight-based ribavirin (tablet; 1000 or 1200 mg divided twice a day) up to 24 weeks
Measure Participants	213
Number [percentage of participants]	0.9 0.4%

7. Secondary Outcome

Title	Percentage of Participants Meeting Premature Study Drug Discontinuation Criteria
Description	Premature study drug discontinuation was defined as participants who prematurely discontinued study drug with no on-treatment virologic failure.
Time Frame	12 weeks after the last actual dose of study drug

Outcome Measure Data

Analysis Population Description

Core population: Participants meeting all inclusion criteria and who were adequately treated according to the standard of care and within local label recommendations for their specific disease characteristics (cirrhotic status, genotype).

Arm/Group Title	Participants With HCV Genotype 1 or 4
Arm/Group Description	Ombitasvir/paritaprevir/ritonavir (two 12.5 mg/75 mg/50 mg co-formulated tablets once daily); ± dasabuvir (tablet; 250 mg twice daily); ± weight-based ribavirin (tablet; 1000 or 1200 mg divided twice a day) up to 24 weeks
Measure Participants	213
Number [percentage of participants]	2.3 1.1%

8. Secondary Outcome

Title	Percentage of Participants With Missing Sustained Virologic Response 12 Weeks Post-Treatment (SVR12) Data and/or Nonresponders Who Did Not Meet Specific SVR12 Nonresponder Criteria
Description	The number of participants with missing SVR12 data or SVR12 nonresponder participants who did not meet criteria for on-treatment virologic failure, relapse, premature treatment discontinuation, and who did not have an Insufficient virological response was documented.
Time Frame	12 weeks after the last actual dose of study drug

Outcome Measure Data

Analysis Population Description

Core population: Participants meeting all inclusion criteria and who were adequately treated according to the standard of care and within local label recommendations for their specific disease characteristics (cirrhotic status, genotype).

Arm/Group Title	Participants With HCV Genotype 1 or 4
Arm/Group Description	Ombitasvir/paritaprevir/ritonavir (two 12.5 mg/75 mg/50 mg co-formulated tablets once daily); ± dasabuvir (tablet; 250 mg twice daily); ± weight-based ribavirin (tablet; 1000 or 1200 mg divided twice a day) up to 24 weeks
Measure Participants	213
Number [percentage of participants]	3.8 1.8%

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	Participants With HCV Genotype 1 or 4
Arm/Group Description	Ombitasvir/paritaprevir/ritonavir (two 12.5 mg/75 mg/50 mg co-formulated tablets once daily); ± dasabuvir (tablet; 250 mg twice daily); ± weight-based ribavirin (tablet; 1000 or 1200 mg divided twice a day) up to 24 weeks
All Cause Mortality
	Participants With HCV Genotype 1 or 4
	Affected / at Risk (%)	# Events
Total	0/216 (0%)
Serious Adverse Events
	Participants With HCV Genotype 1 or 4
	Affected / at Risk (%)	# Events
Total	7/216 (3.2%)
Blood and lymphatic system disorders
Anaemia	1/216 (0.5%)
Cardiac disorders
Acute myocardial infarction	1/216 (0.5%)
Investigations
Blood bilirubin increased	1/216 (0.5%)
Nervous system disorders
Hepatic encephalopathy	1/216 (0.5%)
Psychiatric disorders
Mental disorder	1/216 (0.5%)
Suicidal ideation	1/216 (0.5%)
Social circumstances
Substance use	1/216 (0.5%)
Other (Not Including Serious) Adverse Events
	Participants With HCV Genotype 1 or 4
	Affected / at Risk (%)	# Events
Total	21/216 (9.7%)
Blood and lymphatic system disorders
Anaemia	8/216 (3.7%)
Cardiac disorders
Acute myocardial infarction	1/216 (0.5%)
Gastrointestinal disorders
Vomiting	1/216 (0.5%)
Hepatobiliary disorders
Hyperbilirubinaemia	2/216 (0.9%)
Hepatic failure	1/216 (0.5%)
Infections and infestations
Helicobacter infection	1/216 (0.5%)
Investigations
Blood bilirubin increased	1/216 (0.5%)
Nervous system disorders
Hepatic encephalopathy	1/216 (0.5%)
Hypoaesthesia	1/216 (0.5%)
Psychiatric disorders
Mental disorder	1/216 (0.5%)
Suicidal ideation	1/216 (0.5%)
Skin and subcutaneous tissue disorders
Pruritus	3/216 (1.4%)
Rash pruritic	1/216 (0.5%)
Social circumstances
Substance use	1/216 (0.5%)

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.