Clinical Trial Results:
HepNet pilot trial: Multicenter trial for the treatment of chronic hepatitis E with sofosbuvir (SofE)
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Summary
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EudraCT number |
2017-000403-24 |
Trial protocol |
DE |
Global end of trial date |
18 Feb 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
23 Sep 2022
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First version publication date |
23 Sep 2022
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Other versions |
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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 |
HepNet-SofE
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03282474 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Hannover Medical School
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Sponsor organisation address |
Carl-Neuberg-Str. 1, Hannover, Germany, 30625
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Public contact |
Stabsstelle Qualitätsmanagement in der Klinischen Forschung, Hannover Medical School, EudraCT@mh-hannover.de
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Scientific contact |
Stabsstelle Qualitätsmanagement in der Klinischen Forschung, Hannover Medical School, EudraCT@mh-hannover.de
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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 |
08 Apr 2019
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
18 Feb 2019
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Global end of trial reached? |
Yes
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Global end of trial date |
18 Feb 2019
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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 antiviral efficacy of sofosbuvir (SOF) against HEV as measured by the proportion of subjects who become HEV RNA negative (HEV RNA undetectable) after 24 weeks of therapy
• To evaluate the safety and tolerability of SOF-containing regimens administered for up to 24 weeks in patients with chronic HEV infection
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Protection of trial subjects |
Withdrawal possible when patient´s safety or wellbeing is compromised.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
07 Dec 2017
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Long term follow-up planned |
No
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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 |
Germany: 10
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Worldwide total number of subjects |
10
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EEA total number of subjects |
10
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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) |
10
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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 |
Recruitment between 12/2017 and 02/2019 at 3 sites in Germany (Hannover Medical School, Hannover and University Medical Center Hamburg-Eppendorf, Hamburg and Charité Campus Virchow-Klinikum, Berlin). | ||||||||||
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Pre-assignment
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Screening details |
- | ||||||||||
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Pre-assignment period milestones
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Number of subjects started |
12 [1] | ||||||||||
Number of subjects completed |
10 | ||||||||||
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Pre-assignment subject non-completion reasons
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Reason: Number of subjects |
Inclusion/ Exclusion criteria: 2 | ||||||||||
| Notes [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: 12 patients were screened for enrolment and 10 patients finally were enrolled in the study. 2 patients dit not met inclusion-/ exclusion criteria and thus must be excluded as screening failure. The number of patients in the baseline period reflects the number of patients who received at least one dose of study medication (ITT). |
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Period 1
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Period 1 title |
ITT Population (overall period)
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||
Blinding implementation details |
This was a prospective open-label, single-arm, multicenter, phase II pilot trial of SOF in subjects with chronic HEV infection.
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Arms
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Arm title
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Single Arm | ||||||||||
Arm description |
Single Arm Study - Sofosbuvir, 400 mg, film-coated tablets (Sovaldi® 400mg, study-specific labelled | ||||||||||
Arm type |
Active comparator | ||||||||||
Investigational medicinal product name |
Sofosbuvir
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Investigational medicinal product code |
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Other name |
Sovaldi
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Sofosbuvir, 400 mg, film-coated tablets (Sovaldi® 400mg, study-specific labelled) once per day
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Baseline characteristics reporting groups
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Reporting group title |
ITT Population
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Reporting group description |
The ITT population consisting of all patients who received at least on dose of the study medication. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
PP Population
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
One patient was a screening failure who received medication but retesting of screening sample showed negative HEV RNA. The patient stopped intake of study medication after 22 weeks.
One Patient died before completing the study and was excluded from the per protocol analysis.
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Subject analysis set title |
Efficacy Population
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Subject analysis set type |
Sub-group analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
One patient 01-02 was a screening failure who received medication but retesting of screening sample showed negative HEV RNA. The patient stopped intake of study medication after 22 weeks. Therefore this patient was excluded from the efficacy analyses as the primary endpoint was the proportion of HEV RNA negative patients after 24 weeks of therapy. Including this patient in the efficacy analyses would promote the primary objective of the trial because the patient was not HEV RNA positive at the beginning of treatment, and, in consequence, no clearing of the virus was possible.
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End points reporting groups
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Reporting group title |
Single Arm
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Reporting group description |
Single Arm Study - Sofosbuvir, 400 mg, film-coated tablets (Sovaldi® 400mg, study-specific labelled | ||
Subject analysis set title |
PP Population
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
One patient was a screening failure who received medication but retesting of screening sample showed negative HEV RNA. The patient stopped intake of study medication after 22 weeks.
One Patient died before completing the study and was excluded from the per protocol analysis.
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Subject analysis set title |
Efficacy Population
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
One patient 01-02 was a screening failure who received medication but retesting of screening sample showed negative HEV RNA. The patient stopped intake of study medication after 22 weeks. Therefore this patient was excluded from the efficacy analyses as the primary endpoint was the proportion of HEV RNA negative patients after 24 weeks of therapy. Including this patient in the efficacy analyses would promote the primary objective of the trial because the patient was not HEV RNA positive at the beginning of treatment, and, in consequence, no clearing of the virus was possible.
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End point title |
HEV RNA negativity after 24 weeks of therapy | |||||||||
End point description |
Proportion of subjects who become HEV RNA negative after 24 weeks of therapy
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End point type |
Primary
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End point timeframe |
24 weeks after therapy
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Statistical analysis title |
two-sided 95%-Wilson-confidence interval | |||||||||
Statistical analysis description |
The two-sided 95%-Wilson-confidence interval for the proportion of subjects with sustained viral response after 24 weeks of therapy with SOF will be evaluated. Since it is assumed that 5 out of 10 patients (ITT or PP) will be HEV-RNA negative by that time, the lower limit of the confidence interval is expected to be above 20%. Missing
values for the primary endpoint (HEV RNA negativity after 24 weeks of therapy) will be counted as Treatment failures.
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Comparison groups |
Efficacy Population v PP Population
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Number of subjects included in analysis |
17
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Analysis specification |
Pre-specified
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Analysis type |
other | |||||||||
P-value |
≤ 0.2 [1] | |||||||||
Method |
95%Wilson-confidence interval | |||||||||
Confidence interval |
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| Notes [1] - H0: The proportion of HEV RNA negative patients after 24 weeks of therapy with SOF is lower than or equal to 20%. H1: The proportion of HEV RNA negative patients after 24 weeks of therapy with SOF is higher than 20%. |
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End point title |
Proportion of subjects who are HEV RNA negative 12 weeks after discontinuation of therapy | ||||||
End point description |
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End point type |
Secondary
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End point timeframe |
12 weeks after discontinuation of therapy
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| No statistical analyses for this end point | |||||||
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End point title |
Additional efficacy evaluations include HEV RNA change from baseline during therapy | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
End of Treatment - week 24
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| No statistical analyses for this end point | |||||||||
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End point title |
Proportion of subject who reached ALT normalization after 12 weeks of therapy | ||||||
End point description |
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End point type |
Secondary
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End point timeframe |
12 weeks of therapy
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| No statistical analyses for this end point | |||||||
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End point title |
Proportion of subject who reached ALT normalization after 24 weeks of therapy | ||||||
End point description |
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End point type |
Secondary
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End point timeframe |
24 weeks
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| Notes [2] - Patient died before the end of the study |
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| No statistical analyses for this end point | |||||||
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End point title |
Proportion of subject who reached ALT normalization 12 weeks after discontinuation of therapy (FU12 visit) | ||||||
End point description |
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End point type |
Secondary
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End point timeframe |
12 after discontinuation of therapy
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| Notes [3] - Patient died before the end of the study |
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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 |
The AE documentation period for this trial begins with informed consent and ends with the 12 weeks post-treatment visit.
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Adverse event reporting additional description |
Numbers in the non-serious adverse events section reflect all adverse events occurring during the study (non-serious and serious).
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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 |
20.1
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Reporting groups
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Reporting group title |
Sofosbuvir
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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13 Dec 2017 |
No. 1.0 (resulting in study protocol version 2.0 of 13.12.2017) covered the following major changes:
• Change of coordinating investigator
• Addition of an examination during post-treatment visit
• Specification of statistical methods |
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20 Sep 2018 |
No. 1.1 (resulting in study protocol version 3.0 of 20.09.2018) covered the following major changes:
• Possibility of data collection of diagnosis relevant laboratory values of pre-screening examinations has been included
• Update of contact information |
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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 | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/32624195 |
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