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
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Triple Combination Therapy Participants who demonstrated genotype 1 chronic hepatitis C infection and had a history of unsuccessful treatment with pegylated interferon (peginterferon) alfa + ribavirin, and who were subjected to receive a triple combination therapy with simeprevir or boceprevir plus peginterferon alfa-2a and ribavirin were observed. |
Drug: Boceprevir
Boceprevir administered according to corresponding summary of product characteristics (SmPC).
Other Names:
Drug: Simeprevir
Simeprevir administered according to corresponding summary of product characteristics (SmPC).
Other Names:
Drug: Pegylated Interferon (Peginterferon) Alfa-2a
Pegylated interferon (peginterferon) alfa-2a according to corresponding summary of product characteristics (SmPC).
Other Names:
Drug: Ribavirin
Ribavirin according to corresponding summary of product characteristics (SmPC).
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
- 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.
- 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.
- 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.
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Budapest | Hungary | 1097 | ||
| 2 | Budapest | Hungary | 1125 | ||
| 3 | Békéscsaba | Hungary | 5600 | ||
| 4 | Debrecen | Hungary | 4032 | ||
| 5 | Eger | Hungary | 3300 | ||
| 6 | Kaposvár | Hungary | 7400 | ||
| 7 | Szombathely | Hungary | 8800 |
Sponsors and Collaborators
- Hoffmann-La Roche
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ML29278
Study Results
Participant Flow
| Recruitment Details | A total of 19 participants were enrolled in 8 study centers. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Triple Combination Therapy |
|---|---|
| Arm/Group Description | 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. |
| Period Title: Overall Study | |
| STARTED | 19 |
| COMPLETED | 3 |
| NOT COMPLETED | 16 |
Baseline Characteristics
| Arm/Group Title | Triple Combination Therapy |
|---|---|
| Arm/Group Description | 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. |
| Overall Participants | 19 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
52.73
(10.85)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
10
52.6%
|
| Male |
9
47.4%
|
Outcome Measures
| Title | Sustained Virological Response 24 (SVR24) Rate |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Triple Combination Therapy |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 1 |
| Number [percentage of participants] |
0
0%
|
| Title | Percentage of Participants With Virological Response |
|---|---|
| Description | Virological response is defined as HCV RNA <15 IU/mL. |
| Time Frame | Weeks 4, 8, 12, and 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat (ITT) population included all enrolled participants. Here, 'n' indicated number of participants with virological response data at evaluated time points. |
| Arm/Group Title | Triple Combination Therapy |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 19 |
| Week 4 (n=3) |
0.0
0%
|
| Week 8 (n=18) |
73.7
387.9%
|
| Week 12 (n=17) |
73.7
387.9%
|
| Week 24 (n=16) |
78.9
415.3%
|
| Title | Number of Participants With Virological Breakthrough |
|---|---|
| Description | 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. |
| Time Frame | Up to Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all enrolled participants. |
| Arm/Group Title | Triple Combination Therapy |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 19 |
| Number [participants] |
1
5.3%
|
| Title | Number of Participants With Virological Relapse |
|---|---|
| Description | 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. |
| Time Frame | Week 49 up to Week 72 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all enrolled participants. |
| Arm/Group Title | Triple Combination Therapy |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 19 |
| Number [participants] |
1
5.3%
|
| Title | Number of Participants With Treatment Discontinuation Due to Futility |
|---|---|
| Description | 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. |
| Time Frame | Up to Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all enrolled participants. |
| Arm/Group Title | Triple Combination Therapy |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 19 |
| Number [participants] |
2
10.5%
|
| Title | Number of Participants With Treatment Discontinuation |
|---|---|
| Description | 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. |
| Time Frame | Up to Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all enrolled participants. |
| Arm/Group Title | Triple Combination Therapy |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 19 |
| Sponsor's decision |
7
36.8%
|
| Adverse event |
4
21.1%
|
| Futility rule |
2
10.5%
|
| Title | Number of Participants With Adverse Events |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all enrolled participants. |
| Arm/Group Title | Triple Combination Therapy |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 19 |
| Number [participants] |
17
89.5%
|
| Title | Percentage of Participants With Positive Predictive Value of Participant Demographics for SVR Rate |
|---|---|
| Description | Demographic characteristics recorded were age and gender. Predictive value of these characteristics for SVR rate was to be assessed. |
| Time Frame | Screening (before Week 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Predictive values of participant demographics could not be analyzed as the SVR24 rate was based on one participant. |
| Arm/Group Title | Triple Combination Therapy |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 0 |
| Title | Percentage of Participants With Positive Predictive Value of Liver Fibrosis |
|---|---|
| Description | 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. |
| Time Frame | Screening (before Week 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Predictive values of sub-categories of liver fibrosis could not be analyzed as the SVR24 rate was based on one participant. |
| Arm/Group Title | Triple Combination Therapy |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 0 |
| Title | Predictive Value of HCV Disease Characteristics |
|---|---|
| Description | 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. |
| Time Frame | Screening (before Week 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Predictive values of HCV disease characteristics could not be analyzed as the SVR24 rate was based on one participant. |
| Arm/Group Title | Triple Combination Therapy |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 0 |
| Title | Percentage of Participants With Positive Predictive Value of Previous Virological Response (Null-response, Partial Response, or Relapse) |
|---|---|
| Description | 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. |
| Time Frame | Up to 72 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Predictive values of previous virological response could not be analyzed as the SVR24 rate was based on one participant. |
| Arm/Group Title | Triple Combination Therapy |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 0 |
Adverse Events
| Time Frame | From signing of informed consent form up to the end of study (up to 72 weeks) | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Triple Combination Therapy | |
| Arm/Group Description | Participants who demonstrated genotype 1 chronic hepatitis C infection and had a history of unsuccessful treatment with pegylated interferon (Peg-interferon) alfa + ribavirin, and who were subjected to receive a triple combination therapy with simeprevir or boceprevir plus peg-interferon alfa-2a and ribavirin were observed. | |
All Cause Mortality |
||
| Triple Combination Therapy | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Triple Combination Therapy | ||
| Affected / at Risk (%) | # Events | |
| Total | 5/19 (26.3%) | |
| Blood and lymphatic system disorders | ||
| Anaemia | 3/19 (15.8%) | |
| Neutropenia | 1/19 (5.3%) | |
| Thrombocytopenia | 1/19 (5.3%) | |
| Gastrointestinal disorders | ||
| Ileus | 1/19 (5.3%) | |
| Infections and infestations | ||
| Administration site cellulitis | 1/19 (5.3%) | |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||
| Oesophageal carcinoma | 1/19 (5.3%) | |
Other (Not Including Serious) Adverse Events |
||
| Triple Combination Therapy | ||
| Affected / at Risk (%) | # Events | |
| Total | 14/19 (73.7%) | |
| Blood and lymphatic system disorders | ||
| Anemia | 8/19 (42.1%) | |
| Neutropenia | 1/19 (5.3%) | |
| Thrombocytopenia | 3/19 (15.8%) | |
| Endocrine disorders | ||
| Hypothyroidism | 1/19 (5.3%) | |
| Gastrointestinal disorders | ||
| Aphthous ulcer | 1/19 (5.3%) | |
| Gastrooesophageal reflux disease | 1/19 (5.3%) | |
| Vomiting | 1/19 (5.3%) | |
| Nausea | 1/19 (5.3%) | |
| Faeces soft | 1/19 (5.3%) | |
| General disorders | ||
| Influenza like illness | 1/19 (5.3%) | |
| Fatigue | 3/19 (15.8%) | |
| Oedema peripheral | 1/19 (5.3%) | |
| Nervous system disorders | ||
| Headache | 1/19 (5.3%) | |
| Dysgeusia | 4/19 (21.1%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| Cough | 1/19 (5.3%) | |
| Epistaxis | 1/19 (5.3%) | |
| Skin and subcutaneous tissue disorders | ||
| Rash | 2/19 (10.5%) | |
| Dermatitis | 1/19 (5.3%) | |
| Hyperhidrosis | 1/19 (5.3%) | |
| Pruritus | 2/19 (10.5%) | |
| Alopecia | 1/19 (5.3%) | |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
| Name/Title | Medical Communications |
|---|---|
| Organization | Hoffmann-La Roche |
| Phone | 800 821-8590 |
| genentech@druginfo.com |
- ML29278