Clinical Trial Results:
Multicenter trial for the treatment of acute Hepatitis C for 8 weeks with Sofosbuvir/Velpatasvir fix dose combination - The HepNet Acute HCV-V study
|
Summary
|
|
EudraCT number |
2018-003474-27 |
Trial protocol |
DE |
Global end of trial date |
08 Jun 2021
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
23 Sep 2022
|
First version publication date |
23 Sep 2022
|
Other versions |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
HepNet-aHCV-V
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT03818308 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
Hannover Medical School
|
||
Sponsor organisation address |
Carl-Neuberg-Str. 1, Hannover, Germany, 30625
|
||
Public contact |
Stabsstelle Qualitätsmanagement in der Klinischen Forschung, Hannover Medical School, EudraCT@mh-hannover.de
|
||
Scientific contact |
Stabsstelle Qualitätsmanagement in der Klinischen Forschung, Hannover Medical School, EudraCT@mh-hannover.de
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
08 Sep 2021
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
08 Jun 2021
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
08 Jun 2021
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
• To evaluate the efficacy of treatment with sofosbuvir/velpatasvir (SOF/VEL) Fixed-Dose Combination (FDC) for 8 weeks in patients with acute HCV infection as measured by the proportion of subjects with sustained viral response (undetectable HCV RNA) 12 weeks after stop of therapy (SVR 12)
|
||
Protection of trial subjects |
Before study enrolment all subjects got detailed information about study procedures, potential risks and benefits as well as alternative treatment options. The study was approved by regulatory authorities and independent monitoring was conducted to ensure subjects safety. The IMP is an approved drug with extensive data from clinical trials and favorable risk-benefit profile.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
26 Jun 2019
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Germany: 31
|
||
Worldwide total number of subjects |
31
|
||
EEA total number of subjects |
31
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
31
|
||
From 65 to 84 years |
0
|
||
85 years and over |
0
|
||
|
|||||||||||||
|
Recruitment
|
|||||||||||||
Recruitment details |
Patints were screened in 14 study centers in Germany. Overall 31 patients were screened for elegibility and signed informed consent. 11 of these screened patients had to be excluded due to inclusion/exclusion criteria (Screening failures). Recruitment period was between 06/2019 and 01/2020. | ||||||||||||
|
Pre-assignment
|
|||||||||||||
Screening details |
Adults (≥18 years) with acute HCV monoinfection. Leading inclusion criteria were HCV RNA > 10³ IU/ml and proven antibody or RNA seroconversion or ALT > 10 ULN with known exposure within 4 month. Leading exclusion criteria were HIV co-infection, clinically significant illness (other than HCV) and contraindications against SOF/VEL. | ||||||||||||
|
Pre-assignment period milestones
|
|||||||||||||
Number of subjects started |
31 | ||||||||||||
Number of subjects completed |
20 | ||||||||||||
|
Pre-assignment subject non-completion reasons
|
|||||||||||||
Reason: Number of subjects |
Screening Failure: 11 | ||||||||||||
|
Period 1
|
|||||||||||||
Period 1 title |
ITT Population (overall period)
|
||||||||||||
Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Not applicable
|
||||||||||||
Blinding used |
Not blinded | ||||||||||||
|
Arms
|
|||||||||||||
|
Arm title
|
single-arm | ||||||||||||
Arm description |
single-arm study | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Epclusa®
|
||||||||||||
Investigational medicinal product code |
|||||||||||||
Other name |
sofosbuvir/ velpatasvir
|
||||||||||||
Pharmaceutical forms |
Film-coated tablet
|
||||||||||||
Routes of administration |
Oral use
|
||||||||||||
Dosage and administration details |
Sofosbuvir/ velpatasvir (SOF/VEL, Epclusa®), film-coated, fixed-dose combination tablet, consisting of 400 mg SOF and 100 mg VEL for oral administration
|
||||||||||||
|
|||||||||||||
| Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: 31 patients were screened for enrolment and 20 patients finally were enrolled in the study. 11 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). |
|||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
ITT Population
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
The overall population is an ITT population and consists of all patients who received at least one dose of the study medication. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Subject analysis sets
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
PP Population
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The PP population comprises of all patients that were complying with the studyprotocol until the end of the observational period, particularly all patients that attended all study visits and have fully observed data for the primary endpoint.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
single-arm
|
||
Reporting group description |
single-arm study | ||
Subject analysis set title |
PP Population
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
The PP population comprises of all patients that were complying with the studyprotocol until the end of the observational period, particularly all patients that attended all study visits and have fully observed data for the primary endpoint.
|
||
|
|||||||||||||
End point title |
Proportion of subjects with sustained virological response (SVR 12) 12 weeks after discontinuation of therapy | ||||||||||||
End point description |
Proportion of subjects with sustained virological response (undetectable HCV RNA) 12 weeks after discontinuation of therapy (SVR 12)
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Follow up visit 12
|
||||||||||||
|
|||||||||||||
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 12 weeks after discontinuation of therapy (SVR 12). Since it is assumed that all patients will be HCV RNA negative, it is expected that the corresponding 95%-Wilson-confidence interval will be above 83% and it can be concluded that the treatment has an efficacy of at least 83% 12 weeks after a treatment period of 8 weeks. H0: pSVR12 < 0.83 and H1: pSVR12 ≥ 0.83.
|
||||||||||||
Comparison groups |
single-arm v PP Population
|
||||||||||||
Number of subjects included in analysis |
38
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other [1] | ||||||||||||
P-value |
< 0.83 [2] | ||||||||||||
Method |
95%Wilson-confidence interval | ||||||||||||
Confidence interval |
|||||||||||||
| Notes [1] - Patients with missing values for the primary endpoint SVR 12 will be counted as treatment failures for the ITT analysis. These patients are hence counted as patients, which did not show a sustained viral response. [2] - H0: pSVR12 < 0.83 and H1: pSVR12 ≥ 0.83. |
|||||||||||||
|
|||||||
End point title |
Proportion of subjects who reached ALT normalization after End of therapy | ||||||
End point description |
Proportion of subjects who reached ALT normalization (ALT <ULN) after 8 weeks of therapy (EOT)
|
||||||
End point type |
Secondary
|
||||||
End point timeframe |
Week 8
|
||||||
|
|||||||
| No statistical analyses for this end point | |||||||
|
|||||||
End point title |
Proportion of subjects who reached ALT normalization 12 weeks after discontinuation of therapy (FU12) | ||||||
End point description |
Proportion of subjects who reached ALT normalization (ALT <ULN) after 12 weeks after discontinuation of therapy (FU12)
|
||||||
End point type |
Secondary
|
||||||
End point timeframe |
Follow Up Visit 12
|
||||||
|
|||||||
| No statistical analyses for this end point | |||||||
|
|||||||||
End point title |
Mean HCV RNA at week 2 | ||||||||
End point description |
|||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Week 2 after baseline
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Mean HCV RNA at week 4 | ||||||||
End point description |
|||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Week 4 after baseline
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Mean HCV RNA at week 8 | ||||||||
End point description |
|||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Week 8 after baseline
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Mean HCV RNA 12 weeks after end of treatment | ||||||||
End point description |
|||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
12 weeks after end of treatment
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
The adverse event documentation period for this trial begins with informed consent and ends with the 12 weeks post-treatment visit.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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).
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20.1
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
SOF/VEL
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
