Clinical Trial Results:
A Phase IIb, Open Label, Single Arm, Multicenter Study to Evaluate the Effect of 48-weeks Peginterferon alfa-2a (PEG-IFN) Administration on Serum HBsAg in Chronic Hepatitis B, HBeAg-Negative, Genotype D Patients on Treatment with Nucleos(t)ide Analogues (NAs), Showing Stable HBV DNA Suppression.
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Summary
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EudraCT number |
2012-000080-25 |
Trial protocol |
IT |
Global end of trial date |
28 Oct 2015
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Results information
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Results version number |
v2(current) |
This version publication date |
22 Oct 2016
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First version publication date |
10 Jul 2016
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Other versions |
v1 |
Version creation reason |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
ML28262
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01706575 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
F. Hoffmann-La Roche AG
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Sponsor organisation address |
Grenzacherstrasse 124, Basel, Switzerland, CH-4070
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Public contact |
F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
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Scientific contact |
F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
28 Oct 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
30 Sep 2013
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Global end of trial reached? |
Yes
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Global end of trial date |
28 Oct 2015
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the decline in serum Hepatitis B surface Antigen (HBsAg) at the end of combination treatment with Pegylated Interferon (Peginterferon) Alfa-2a (PEG-IFN) and nucleos(t)ide analogues (NA) (Study Week 48).
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Protection of trial subjects |
All study subjects were required to read and sign an informed consent form.
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Background therapy |
Subjects continued to nucleos(t)ide analogues (NA) therapy along with the study medication. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
24 Jan 2013
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety, Efficacy | ||
Long term follow-up duration |
11 Months | ||
Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Italy: 76
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Worldwide total number of subjects |
76
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EEA total number of subjects |
76
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
76
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||
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Pre-assignment
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Screening details |
A total of 76 subjects started the study and were included in lead-in period. Out of 76 subjects, 70 received study drug. Data is reported here for the interim analysis (up to 48 weeks). | ||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||
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Arms
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Arm title
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Pegylated Interferon (Peginterferon) Alfa-2a | ||||||||||||||||
Arm description |
Subjects receiving nucleos(t)ide analogues (NA) therapy with Hepatitis B surface Antigen (HBsAg) decline less than (<) 0.5 log 10 international unit/milliliter (IU/ml) at baseline received peginterferon alfa-2a 180 microgram (mcg), subcutaneously (SC) once weekly for 48 weeks along with their NA therapy. | ||||||||||||||||
Arm type |
Experimental | ||||||||||||||||
Investigational medicinal product name |
Pegylated Interferon (Peginterferon) Alfa-2a
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Peginterferon alfa-2a 180 mcg, subcutaneously (SC) once weekly for 48 weeks.
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Baseline characteristics reporting groups
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Reporting group title |
Pegylated Interferon (Peginterferon) Alfa-2a
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Reporting group description |
Subjects receiving nucleos(t)ide analogues (NA) therapy with Hepatitis B surface Antigen (HBsAg) decline less than (<) 0.5 log 10 international unit/milliliter (IU/ml) at baseline received peginterferon alfa-2a 180 microgram (mcg), subcutaneously (SC) once weekly for 48 weeks along with their NA therapy. | |||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Pegylated Interferon (Peginterferon) Alfa-2a
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Reporting group description |
Subjects receiving nucleos(t)ide analogues (NA) therapy with Hepatitis B surface Antigen (HBsAg) decline less than (<) 0.5 log 10 international unit/milliliter (IU/ml) at baseline received peginterferon alfa-2a 180 microgram (mcg), subcutaneously (SC) once weekly for 48 weeks along with their NA therapy. | ||
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End point title |
Efficacy: Percent Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Titer at End of the Combination Treatment (Week 48) [1] | ||||||||
End point description |
Per-Protocol Population (PP) included all subjects without severe protocol violations, including major inclusion or exclusion criteria violations.
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End point type |
Primary
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End point timeframe |
Baseline up to Week 48
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The statistical analysis was not planned to be reported for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Efficacy: Percentage of Subjects With Serum Hepatitis B Surface Antigen (HBsAg) Decrease >/= 50% From Baseline at End of the Combination Treatment (Week 48) [2] | ||||||||
End point description |
Subjects who stopped pegylated interferon (PEG-IFN) treatment during the add-on phase due to serum HBsAg loss and HBsAg seroconversion were considered as responders.PP included all subjects without severe protocol violations, including major inclusion or exclusion criteria violations and who were undergoing the Week 48 visit.
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End point type |
Primary
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End point timeframe |
Baseline and Week 48
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The statistical analysis was not planned to be reported for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Efficacy: Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Titer at Week 24, 72 and 96 | ||||||||||||||||
End point description |
Change is calculated by HBsAg titer at baseline - HBsAg titer at week of assessments. PP included all subjects without severe protocol violations, including major inclusion or exclusion criteria violations. Here, number of subjects analyzed signifies those subjects who were evaluable for the outcome measure and n signifies the number of subjects who were evaluated at specified time points.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 24, 72 and 96
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Efficacy: Percentage of Subjects With HBsAg Decrease >/=1 log10 IU/ml From Baseline to Week 48 | ||||||||
End point description |
PP included all subjects without severe protocol violations, including major inclusion or exclusion criteria violations and who were undergoing the Week 48 visit.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 48
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| No statistical analyses for this end point | |||||||||
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End point title |
Efficacy: Number of Subjects With Serum HBsAg Loss at Week 12 That Persisted up to Week 96 | ||||||||
End point description |
HBsAg loss is defined as HBsAg less than or equal to (</=) 0.05 IU/ml. PP included all subjects without severe protocol violations, including major inclusion or exclusion criteria violations.
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End point type |
Secondary
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End point timeframe |
Week 12 up to Week 96
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| No statistical analyses for this end point | |||||||||
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End point title |
Efficacy: HBsAg Levels According to Interleukin 28B (IL28B) Genotypes | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Baseline and Week 48
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| Notes [3] - Analysis was not performed for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Efficacy: HBsAg Levels According to Interferon-Inducible Protein 10 (IP-10) Serum Levels | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Baseline and Week 48
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| Notes [4] - Analysis was not performed for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Safety: Percentage of Subjects With Adverse Events (AE) | ||||||||
End point description |
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Safety population included all subjects who received least one dose of the study drug and had at least one post-dose safety assessment.
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End point type |
Secondary
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End point timeframe |
Baseline up to Week 48
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Baseline up to Week 48
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Adverse event reporting additional description |
Safety population included all subjects who received least one dose of the study drug and had at least one post-dose safety assessment.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.1
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Reporting groups
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Reporting group title |
Pegylated Interferon (Peginterferon) Alfa-2a
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Reporting group description |
Subjects receiving nucleos(t)ide analogues (NA) therapy with Hepatitis B surface Antigen (HBsAg)decline less than <0.5 log 10 international unit/milliliter (IU/ml) at baseline received peginterferon alfa-2a 180 microgram (mcg), subcutaneously (SC) once weekly for 48 weeks along with their NA therapy. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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29 May 2014 |
1. Amendment was released to recalculate the sample size.
2. This descriptive analysis of the reduction of HBsAg at week 48 was also introduced with the amendment.
3. The amendment also states that subjects with HBsAg loss and seroconversion according to 2012 European Association for the Study of the Liver (EASL) Hepatitis B Virus (HBV) Guidelines during the add-on period would stop both PEG-INF and NA treatments, enter the follow-up period and be considered as responders. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
