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danoprevir

Phase 2

Hepatitis C, Chronic | Small molecule | Infectious Disease |Roche Holding AG|Last Updated: Nov 2, 2016

Success Probability

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Market & Valuation

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Trial Design

RandomizedPLACEBO_CONTROLLED
Total Trials2
Total Enrollment120

FDA Designations

No designations recorded

Clinical trial landscape

danoprevir · 16 trials · 2 indications

Phase 2 1Phase 1 15
NCT01749150A Study of Ritonavir-Boosted Danoprevir in Combination With Pegasys (Peginterferon Alfa-2a) and Copegus (Ribavirin) in Patients of Asian Origin With Chronic Hepatitis C Genotype 1 With or Without CirrhosisHepatitis C, Chronic
COMPLETED61 Analytics
PHASE2COMPLETED
A Study of Ritonavir-Boosted Danoprevir in Combination With Pegasys (Peginterferon Alfa-2a) and Copegus (Ribavirin) in Patients of Asian Origin With Chronic Hepatitis C Genotype 1 With or Without Cirrhosis
Hepatitis C, ChronicUnlock trial analytics

Study Endpoints

Primary Endpoints

Safety: Incidence of adverse events
approximately 1.5 years
Pharmacokinetics: Area under the concentration-time curve (AUC) for danoprevir/ritonavir
up to 14 days
Antiviral activity: Change in HCV RNA levels, measured using Roche COBAS TaqMan HCV Test v2.0 for High Pure System
from baseline to Week 36/48
Antiviral activity: Proportion of patients with unquantifiable/undetectable HCV RNA during the study
approximately 1.5 years
Pharmacokinetics: Maximum plasma concentration at steady-state (Css,max)
up to 16 days
Pharmacokinetics: Total area under the concentration-time curve form time 0 to 12 hours post-dose at steady-state (AUCss,0-12h)
up to 16 days
Pharmacokinetics: Plasma concentration at steady-state 12 hours post-dose (Css, 12h)
up to 16 days
Pharmacokinetics: Area under the concentration-time curve (AUC)
Pre-dose and up to 12 hours post-dose
Relative bioavailability of danoprevir: Area under the concentration-time curve (AUC)
Pre-dose and up to 24 hours post-dose Days 1, 8 and 15
Pharmacokinetics of ritonavir: Area under the concentration-time curve (AUC)
Pre-dose and up to 24 hours post-dose Days 1, 8 and 15
Pharmacokinetics of efavirenz, danoprevir and ritonavir in coadministration: Cmax
Pre-dose and up to 24 hours post-dose on Days 14 and 28
Pharmacokinetics of efavirenz, danoprevir and ritonavir in coadministration: Area under the concentration-time curve (AUC)
Pre-dose and up to 24 hours post-dose on Days 14 and 28
Effect of coadministration of darunavir (DRV), danoprevir (DNV) and ritonavir (RTV) on DRV/DNV/RTV pharmacokinetics: Area under the concentration-time curve (AUC)
approximately 2 months
Effect of steady-state ritonavir-boosted danoprevir on steady-state raltegravir pharmacokinetics: Area under the concentration-time curve (AUC)
approximately 2 months
Part 1: Danoprevir bioavailabilty (Tablet Formulation 1) in combination with ritonavir (reference formulation): Area under the concentration-time curve (AUC)
24 hours
Part 1: Danoprevir bioavailability (Tablet Formulation 2) in combination with ritonavir (reference formulation): Area under the concentration-time curve (AUC)
24 hours
Part 2: Ritonavir bioavailability (Test Formulation 1) in combination with danoprevir (refernce formulation): Area under the concentration-time curve (AUC)
24 hours
Part 2: Ritonavir bioavailability (Test Formulation 2) in combination with danoprevir (reference formulation): Area under the concentration-time curve (AUC)
24 hours
Effect of single dose of cyclosporine on pharmacokinetics of ritonavir-boosted danoprevir: maximum plasma concentration (Cmax)/area under the concentration-time curve (AUC)
16 time points up to 96 hours
Threshold pharmacological effect on cardiac repolarization as detected by changes in the QT/QTc interval following single dose
approximately 9 weeks
Change in area under the plasma concentration time curve (AUC) of escitalopram
Approximately 4 weeks
Effect of omeprazole on the area under the plasma concentration time curve of danoprevir when co-administered with ritonavir
1 day
Effect of ranitidine on the area under the plasma concentration time curve of danoprevir when co-administered with ritonavir
1 day
Food effect on area under the plasma concentration time curve of danoprevir when co-administered with ritonavir
1 day
Effect of danoprevir/ritonavir on steady state pharmacokinetics (area under the concentration - time curve (AUC)) of methadone
10 days
Pharmacokinetics (plasma concentration) of danoprevir in patients with hepatic impairment
From baseline to day 10
To investigate the interaction between RO5190591/ritonavir and ketoconazole
Day 40
Safety and tolerability: Adverse events, ECG, laboratory parameters
approximately 3 years
Pharmacokinetics: Cmax, AUC, Cmin, Tmax, Cl, T1/2
Days 3-9
Antiviral activity: HCV RNA (COBAS Taqman HCV Test)
from baseline to Day 28

Secondary Endpoints

Incidence of viral resistance to danoprevir
approximately 1.5 years
Rapid virological response (RVR): Proportion of patients with undetectable HCV RNA at Week 4
approximately 1.5 years
Complete early virological response (cEVR): Proportion of patients with undetectable HCV RNA at Week 12
approximately 1.5 years
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Study Design & Arms

MaskingNONE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
with cirrhosisEXPERIMENTAL -
without cirrhosisEXPERIMENTAL -
A: setrobuvirEXPERIMENTAL -
B: setrobuvir + DNV/rEXPERIMENTAL -
Part 1: iv danoprevirEXPERIMENTAL -
Part 1: placeboPLACEBO_COMPARATOR -
Part 2 A: iv danoprevirEXPERIMENTAL -
Part 2 B: oral danoprevirACTIVE_COMPARATOR -
Part 2 C: ritonavirACTIVE_COMPARATOR -
Part 3 D: iv danoprevirEXPERIMENTAL -
Part 3 E: iv danoprevir + cyclosporineEXPERIMENTAL -
DNV + r referenceACTIVE_COMPARATOR -
DNV/r fixed dose combinationEXPERIMENTAL -
A danoprevir+ritonavirACTIVE_COMPARATOR -
B efavirenzACTIVE_COMPARATOR -
C combinationEXPERIMENTAL -
A danoprevirACTIVE_COMPARATOR -
B darunavirPLACEBO_COMPARATOR -
C danoprevir/darunavirEXPERIMENTAL -
Period 1 ControlACTIVE_COMPARATOR -
Period 2 danoprevir/ritonavirEXPERIMENTAL -
Part 1 AACTIVE_COMPARATOR -
Part 1 BEXPERIMENTAL -
Part 1 CEXPERIMENTAL -
Part 2 DACTIVE_COMPARATOR -
Part 2 EEXPERIMENTAL -
Part 2 FEXPERIMENTAL -
DNV/r+cyclosporineEXPERIMENTAL -
cyclosporineACTIVE_COMPARATOR -
danoprevir+ritonavirACTIVE_COMPARATOR -
AEXPERIMENTAL -
BEXPERIMENTAL -
CACTIVE_COMPARATOR -
DPLACEBO_COMPARATOR -
Single armEXPERIMENTAL -
1EXPERIMENTAL -
2EXPERIMENTAL -

Interventions

NameTypeDescription
danoprevir + ritonavirDRUG125 mg danoprevir + 100 mg ritonvir fixed-dose combination tablet, orally b.i.d., 12 weeks
peginterferon alfa-2a [Pegasys]DRUG180 mcg sc weekly, 12 weeks
ribavirin [Copegus]DRUG1000-1200 mg orally daily in divided doses, 12 weeks
danoprevirDRUG100 mg orally every 12 hours
ritonavirDRUG100 mg orally every 12 hours
setrobuvirDRUG200 mg orally every 12 hours
placeboDRUGsingle iv infusion
efavirenzDRUGmultiple oral doses
darunavirDRUG600 mg q12h
raltegravirDRUG400 mg q12h Days 1-4 and 18-21
cyclosporineDRUGSingle oral dose
danoprevir placeboDRUGsingle oral dose
moxifloxacinDRUG400 mg single dose orally
moxifloxacin placeboDRUGsingle oral dose
ritonavir placeboDRUGsingle oral dose
escitalopramDRUGoral doses of escitalopram
omeprazoleDRUGoral doses of omeprazole
ranitidineDRUGoral dose of ranitidine
methadoneDRUGstable maintenance therapy: 20-120 mg daily single oral morning dose
ketoconazoleDRUGRepeated daily doses
ribavirinDRUG1000-1200mg/day po
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites13

Inclusion Criteria: * Adult patients of East Asian or Southeast Asian origin, \>/= 18 years of age * Presence of chronic genotype 1 hepatitis C infection * Treatment-naïve Exclusion Criteria: * History or presence of decompensated liver disease * Presence or history of non-hepatitis C chronic liv...

Countries:South KoreaTaiwanThailandHungaryPolandNetherlandsNew ZealandUnited StatesFranceCzechiaSlovakia
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Frequently asked questions about danoprevir

What is danoprevir used for?

Danoprevir is an investigational small molecule being studied for the treatment of chronic Hepatitis C, specifically in patients with genotype 1 infection. It has also been evaluated in healthy volunteer studies to assess its pharmacokinetics and potential drug interactions. The drug is still in clinical development and has not been approved by regulatory authorities.

Who makes danoprevir?

Danoprevir is being developed by Roche Holding AG, which trades under the ticker RHHBY. The company has sponsored multiple clinical trials evaluating the drug for chronic Hepatitis C and in healthy volunteer studies. Roche is responsible for the drug's development program, including its combination studies with other antiviral agents.

What phase is danoprevir in?

Danoprevir is in Phase 1 clinical development. While some completed trials have explored its use in Hepatitis C patients, the overall development program is at an early stage. The drug remains investigational and is not approved for any use. All 14 trials associated with danoprevir have been completed, with no active trials currently ongoing.

What clinical trials is danoprevir in?

Danoprevir has been studied in several completed clinical trials, including NCT01185860, which evaluated ritonavir-boosted danoprevir with Pegasys and ribavirin in chronic Hepatitis C genotype 1 patients. Other trials include NCT01483729, a bioavailability study in healthy volunteers, and NCT01519336, a drug interaction study with darunavir. All trials are completed.

Is danoprevir the same as RO5190591?

Yes, danoprevir is also known as RO5190591. This alternative name appears in clinical trial records, such as NCT01185860, which refers to ritonavir-boosted danoprevir (RO5190591) in combination with Pegasys and ribavirin. Researchers and investors may encounter either name when reviewing the drug's development history.

How does danoprevir work?

Danoprevir is a small molecule that targets the hepatitis C virus protease enzyme, which is essential for viral replication. By inhibiting this protease, the drug aims to block the virus from multiplying in infected cells. It is often administered with ritonavir, a booster that increases danoprevir's exposure in the body.