An Observational Study Examining the Use of Triple Combination Therapy With Boceprevir, Peginterferon Alfa-2a and Ribavirin in the Re-Treatment of Chronic Hepatitis C Patients

Non-interventional Study to Observe Triple Combination Therapy With Boceprevir or Simeprevir Plus Peginterferon Alfa-2a Plus Ribavirin for Re-treatment of Chronic Hepatitis C in Hungary (IMPERIAL)

Status

Terminated

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT02118597

Enrollment

Registered

2014-04-21

Start date

2014-05-31

Completion date

2015-05-31

Last updated

2016-12-12

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Hepatitis C, Chronic

Brief summary

This prospective, national, multicenter, non-interventional study examined the use of triple combination therapy with boceprevir, pegylated interferon (peginterferon) alfa-2a and ribavirin in re-treating participants with genotype 1 chronic hepatitis C (CHC) infection. Dosing and treatment duration were at the discretion of the investigator in accordance with local clinical practice and local labeling. Participants were to be observed for the duration of their triple combination therapy and for up to 24 weeks thereafter.

Interventions

DRUGBoceprevir

Boceprevir administered according to corresponding summary of product characteristics (SmPC).

DRUGSimeprevir

Simeprevir administered according to corresponding summary of product characteristics (SmPC).

DRUGPegylated Interferon (Peginterferon) Alfa-2a

Pegylated interferon (peginterferon) alfa-2a according to corresponding summary of product characteristics (SmPC).

DRUGRibavirin

Ribavirin according to corresponding summary of product characteristics (SmPC).

Study design

Observational model

CASE_ONLY

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* 18 years of age or over * Genotype 1 CHC infection * Prior unsuccessful treatment with peginterferon alfa plus ribavirin (null-response, partial response and relapsed participants) * Receiving triple combination therapy with boceprevir, peginterferon alfa-2a and ribavirin according to standard of care and in line with local labeling * Enrollment in the study no later than 4 weeks after start of triple combination therapy (including peginterferon alfa-2a and ribavirin lead-in phase)

Exclusion criteria

* Naïve participants not responding to peginterferon alfa plus ribavirin at week 4 (HCV RNA drop \< 1 log10) or at week 12 (HCV RNA \>/= 15 international units/milliliter \[IU/mL\]) and switching to triple combination therapy with boceprevir

Design outcomes

Primary

Measure	Time frame	Description
Sustained Virological Response 24 (SVR24) Rate	24 weeks after end of treatment (EOT) at Week 72	The SVR 24 rate is defined as percentage of participants with Hepatitis C virus (HCV) Ribonucleic Acid (RNA) less than 15 international unit/milliliter (IU/mL) after the 24-weeks follow-up.

Secondary

Measure	Time frame	Description
Percentage of Participants With Virological Response	Weeks 4, 8, 12, and 24	Virological response is defined as HCV RNA \<15 IU/mL.
Number of Participants With Virological Breakthrough	Up to Week 48	Virological breakthrough is defined as either HCV RNA \>=15 IU/mL in participants with prior virological response or as an increase in HCV RNA \>/=1 log10 above nadir.
Number of Participants With Virological Relapse	Week 49 up to Week 72	Virological response is defined as HCV RNA \>/=15 IU/mL during the treatment free follow-up period in participants with virological response at the end of treatment.
Number of Participants With Treatment Discontinuation Due to Futility	Up to Week 48	Treatment discontinuation due to futility is defined as HCV RNA drop \<3 log10 at Week 8, HCV RNA \>/=100 IU/mL at Week 12, or HCV RNA \>/=15 IU/mL at Week 24.
Percentage of Participants With Positive Predictive Value of Previous Virological Response (Null-response, Partial Response, or Relapse)	Up to 72 weeks	Previous virological response was sub-categorized into the following categories: null-response, partial response, or relapse. Predictive value of these sub-categories for SVR rate were to be assessed.
Number of Participants With Adverse Events	Up to 72 weeks	An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Percentage of Participants With Positive Predictive Value of Participant Demographics for SVR Rate	Screening (before Week 1)	Demographic characteristics recorded were age and gender. Predictive value of these characteristics for SVR rate was to be assessed.
Percentage of Participants With Positive Predictive Value of Liver Fibrosis	Screening (before Week 1)	The following sub-categories of liver fibrosis were determined in this study: 1) no cirrhosis, 2) bridging fibrosis and 3) cirrhosis. Predictive value of these sub-categories of liver fibrosis for SVR rate was to be assessed.
Predictive Value of HCV Disease Characteristics	Screening (before Week 1)	HCV disease characteristics evaluated were HCV genotype (subtype), including HCV 1(a) and HCV 1(b). Predictive value of these disease characteristics for SVR rate were to be assessed.
Number of Participants With Treatment Discontinuation	Up to Week 48	Treatment discontinuation is reported by sub-categories of reasons for treatment discontinuation. Futility rule is defined as HCV RNA drop \<3 log10 at Week 8, HCV RNA \>/=100 IU/mL at Week 12, or HCV RNA \>/=15 IU/mL at Week 24.

Countries

Hungary

Participant flow

Recruitment details

A total of 19 participants were enrolled in 8 study centers.

Participants by arm

Arm	Count
Triple Combination Therapy Participants with genotype 1 chronic hepatitis C infection and a history of unsuccessful treatment with pegylated interferon (peginterferon) alfa plus ribavirin, who received a triple combination therapy with boceprevir plus peg-interferon alfa-2a plus ribavirin, were observed.	19
Total	19

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Investigator's decision	1
Overall Study	Serious Adverse Event	1
Overall Study	Sponsor terminated the study	14

Baseline characteristics

Characteristic	Triple Combination Therapy
Age, Continuous	52.73 years STANDARD_DEVIATION 10.85
Sex: Female, Male Female	10 Participants
Sex: Female, Male Male	9 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	14 / 19
serious Total, serious adverse events	5 / 19

Outcome results

Primary

Sustained Virological Response 24 (SVR24) Rate

The SVR 24 rate is defined as percentage of participants with Hepatitis C virus (HCV) Ribonucleic Acid (RNA) less than 15 international unit/milliliter (IU/mL) after the 24-weeks follow-up.

Time frame: 24 weeks after end of treatment (EOT) at Week 72

Population: Due to the early termination of the study follow-up of the vast majority of the participants was not possible and data were not collected. Therefore, results for this outcome measure are based on one participant.

Arm	Measure	Value (NUMBER)
Triple Combination Therapy	Sustained Virological Response 24 (SVR24) Rate	0 percentage of participants

Secondary

Number of Participants With Adverse Events

An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.

Time frame: Up to 72 weeks