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Ombitasvir/ABT-450/Ritonavir

Phase 3

Chronic Hepatitis C | Small molecule | Infectious Disease |AbbVie Inc.|Last Updated: Nov 9, 2017

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedCONTROLLEDBiomarker
Total Trials5
Total Enrollment274
FDA Designations
No designations recorded
Clinical Trials (5)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT02476617Ombitasvir/ABT-450 (Paritaprevir)/Ritonavir With Dasabuvir and Ribavirin (RBV) in Treatment Naive and Treatment Experienced Genotype 1a Hepatitis C Virus Infected AdultsPHASE3 COMPLETED 25Jun 1, 2015Dec 1, 2016Oct 3, 2017 -
NCT02442284A Study to Evaluate the Safety and Efficacy of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir With or Without Ribavirin in US Veterans With Genotype 1 Chronic Hepatitis C Virus InfectionPHASE3 COMPLETED 99May 13, 2015Oct 31, 2016Oct 16, 2017 -
NCT02219477A Study to Evaluate the Safety and Efficacy of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir With Ribavirin in Adults With Genotype 1 and Ombitasvir/Paritaprevir/Ritonavir With Ribavirin in Adults With Genotype 4 Chronic Hepatitis C Virus Infection and Decompensated CirrhosisPHASE3 COMPLETED 36Nov 24, 2014Mar 3, 2017Jul 11, 2017 -
NCT02207088Ombitasvir/ABT-450/Ritonavir and Dasabuvir With or Without Ribavirin in HCV Genotype 1-Infected Adults With Chronic Kidney DiseasePHASE3 COMPLETED 68Sep 23, 2014Dec 6, 2016Nov 9, 2017 -
NCT02493855Ombitasvir/ABT-450/Ritonavir and Dasabuvir Therapy With Low Dose Ribavirin (RBV), Full Dose RBV or RBV Add-On in Treatment Naive Genotype 1a Hepatitis C Virus Infected AdultsPHASE2 COMPLETED 46Jun 1, 2015Dec 1, 2016Oct 31, 2017 -
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Study Endpoints
Primary Endpoints
Change in Interferon (IFN)-Stimulated Genes (ISG) Expression in Peripheral Blood Mononucleated Cells (PBMCs) for Participants Achieving SVR12
Week 0 to Post-Treatment Week 12

The changes from week 0 to post-treatment (PT) week 12 in key ISG expression in PBMCs for participants achieving sustained virologic response 12 weeks PT (SVR12) where SVR12 was defined as 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. For each key ISG, fold change was defined as the ratio of the difference between PT Week 12 and baseline expressions over the baseline expression.

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 after backwards imputation were imputed as nonresponders.

Percentages of Participants With Sustained Virologic Response 12 Weeks Post-Treatment (SVR12) in Group 1 and in Group 2
12 weeks after the last actual dose of study drug

SVR12, defined as HCV RNA \< lower limit of quantification (LLOQ) in the SVR12 window (12 weeks after the last actual dose of study drug) without any confirmed quantifiable (≥ LLOQ) post-treatment value before or during that SVR window. Flanking imputation: for participants with missing HCV RNA at a visit who have an undetectable HCV RNA or unquantifiable HCV RNA at the preceding visit and the succeeding visit, the missing value was imputed as undetectable or unquantifiable. For SVR analyses, if there was no value in the window after the flanking imputation but there was an HCV RNA value after the window, then it was imputed into the SVR window. After above imputations were applied, if there was still no value in the window but there was an HCV RNA value from a local laboratory present, then it was imputed into the SVR window. Otherwise, participants with missing data were counted as failures. The 95% confidence interval was calculated using the Wilson score method.

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.

Slope of the Second Phase Decline in Plasma HCV Ribonucleic Acid (RNA) Levels During Treatment
From Week 0 to Week 2

HCV viral kinetics in plasma during therapy were modeled through non-linear mixed effect models, including a rapid first phase of initial decline and a slower second phase decline. The slope of the second phase decline was estimated for each treatment arm.

Secondary Endpoints
Percentage of Participants With Virologic Failure During Treatment
up to 12 weeks (for 12-week treatment group) or up to 24 weeks (for 24-week treatment group
Percentage of Participants With Post-treatment Relapse
From the end of treatment through 12 weeks after the last dose of study drug
Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) Among Participants With Ongoing Psychiatric Disorders
12 weeks after the last actual dose of study drug
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Study Design & Arms
AllocationNA
MaskingNONE
ModelSINGLE_GROUP
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
Ombitasvir/paritaprevir/ritonavir + dasabuvir + RBVEXPERIMENTALOmbitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg once daily \[QD\]) + dasabuvir (250 mg twice daily \[BID\]) + weight based Ribavirin (RBV; dosed 1,000 or 1,200 mg daily divided BID)
3-DAA ± RBV for 12 or 24 weeksEXPERIMENTAL3-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, dosed as per label based on genotype and presence of cirrhosis.
Group 1: GT1BEXPERIMENTALombitasvir/paritaprevir/ritonavir 25/150/100 mg once daily (QD) + dasabuvir 250 mg twice daily (BID) + ribavirin (RBV) for 12 weeks in hepatitis C virus (HCV) genotype (GT) 1b-infected participants
Group 2: GT1 Non-BEXPERIMENTALombitasvir/paritaprevir/ritonavir 25/150/100 mg QD + dasabuvir 250 mg BID + RBV for 24 weeks in HCV GT1non-b (including GT1a)-infected participants
Group 3: GT4EXPERIMENTALombitasvir/paritaprevir/ritonavir 25/150/100 mg QD + RBV for 24 weeks in HCV GT4-infected participants
3-DAA (Direct Acting Antivirals) with or without RBVEXPERIMENTAL3-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
Arm A: Ribavirin Full Dose for Last 10 WeeksEXPERIMENTALParticipants received ombitasvir/ABT-450/ritonavir 25 mg/150 mg/100 mg once daily (QD) + dasabuvir 250 mg twice daily (BID) for 12 weeks and weight-based ribavirin (1000 mg or 1200 mg split BID) for the last 10 weeks.
Arm B: Ribavirin Full Dose for 12 WeeksEXPERIMENTALParticipants received ombitasvir/ABT-450/ritonavir 25 mg/150 mg/100 mg once daily (QD) + dasabuvir 250 mg twice daily (BID) and weight-based ribavirin (1000 mg or 1200 mg split BID) for 12 weeks.
Arm C: Ribavirin Low-dose for 12 WeeksEXPERIMENTALParticipants received ombitasvir/ABT-450/ritonavir 25 mg/150 mg/100 mg once daily (QD) + dasabuvir 250 mg twice daily (BID) and 600 mg ribavirin once daily for 12 weeks.
Interventions
NameTypeDescription
ombitasvir/paritaprevir/ritonavirDRUGombitasvir/ABT-450/ritonavir tablets
dasabuvirDRUGdasabuvir tablets
ribavirinDRUGribavirin tablets
ombitasvir/paritaprevir/ritonavir and dasabuvirDRUGTablet; ombitasvir coformulated with paritaprevir and ritonavir, dasabuvir tablet
Ombitasvir/ABT-450/RitonavirDRUGOmbitasvir/ABT-450/ritonavir combination tablets
Ribavirin (RBV)DRUGRibavirin tablets
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Eligibility Criteria
Age Range18 Years — 100 Years
SexALL
Healthy VolunteersNo

Inclusion Criteria: 1. Screening laboratory result indicating hepatitis C viral (HCV) genotype (GT) 1a infection. 2. Chronic HCV infection. 3. Participants must be non-cirrhotic. 4. Participants must be treatment-naïve or have documentation that they were adherent to prior pegIFN/RBV combination th...

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