UMIN-CTR Clinical Trial

Basic information
Public title	Effect of Sofosbuvir or Ledipasvir/Sofosbuvir Therapy on Liver Fibrosis in Japanese Patients with Hepatitis C Virus Infection
Acronym	sofosbuvir
Scientific Title	Effect of Sofosbuvir or Ledipasvir/Sofosbuvir Therapy on Liver Fibrosis in Japanese Patients with Hepatitis C Virus Infection
Scientific Title:Acronym	sofosbuvir
Region	Japan

Condition
Condition	chronic hepatitis C
Classification by specialty	Hepato-biliary-pancreatic medicine
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	This study was designed to evaluate the effect of sofosbuvir or sofosbuvir/ledipasvir therapy on liver fibrosis based on FastLec-Hepa (M2BPGi) as well as analysis of other fibrosis markers, in patients with HCV infection who achieved sustained virologic response (SVR) with the therapy.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2	Pragmatic
Developmental phase	Not applicable

Assessment
Primary outcomes	To evaluate the regression of liver fibrosis in patients with HCV infection who have achieved SVR with sofosbuvir or ledipasvir/sofosbuvir at Week 48 after treatment initiation. Liver fibrosis was measured using multiple tests, including FastLec-Hepa and analysis of other fibrosis markers (platelet count, hyaluronic acid, the FIB-4 index, type IV collagen, Fibroscan, SWE).
Key secondary outcomes	1.To evaluate the regression of liver fibrosis in patients HCV infection who have achieved SVR with sofosbuvir or ledipasvir/sofosbuvir at Week 4, 8, 12, 24, and 36 after treatment initiation (FastLec-Hepa (M2BPGi), platelet count, hyaluronic acid, the FIB-4 index, type IV collagen, Fibroscan, SWE). 2.Safety 3.SVR12 rate, SVR24 rate 4.HCC incidence rate

Base
Study type	Observational

Study design
Basic design
Randomization
Randomization unit
Blinding
Control
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms
Purpose of intervention
Type of intervention
Interventions/Control_1
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	20 years-old <=
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	1.Subjects chronically infected with HCV genotype 1 or 2 2.At least 20-years-old at the time of providing consent 3. No documented or suspected HCC by US, CT, or MRI within 6 months prior to the screening 4.Subjects who were fully informed of and understood the objectives, procedures, and risks of the study, and who provided written voluntary consent to participate in the study
Key exclusion criteria	1.Co-infection with hepatitis B virus or human immunodeficiency virus, other chronic liver disease 2.Evidence of hepatic decompensation (Child-Pugh classification B or C). 3.Using interferon and ribavirin during this study
Target sample size	100

Research contact person
Name of lead principal investigator	1st name Middle name Last name Akito Nozaki
Organization	Yokohama City University Medical Center
Division name	Medicine, Gastroenterological Center
Zip code
Address	4-57 Urafune-cho, Minami-ku, Yokohama City, 232-0024, Japan
TEL	045-261-5656
Email	akino@yokohama-cu.ac.jp

Public contact
Name of contact person	1st name Middle name Last name Akito Nozaki
Organization	Yokohama City University Medical Center
Division name	Medicine, Gastroenterological Center
Zip code
Address	4-57 Urafune-cho, Minami-ku, Yokohama City, 232-0024, Japan
TEL	045-261-5656
Homepage URL
Email	akino@yokohama-cu.ac.jp

Sponsor
Institute	Yokohama City University Medical Center
Institute
Department

Funding Source
Organization	Gilead Sciences K.K
Organization
Division
Category of Funding Organization	Profit organization
Nationality of Funding Organization	United States of America

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization
Address
Tel
Email

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions	横浜市立大学附属市民総合医療センター（神奈川県） 横浜市立大学附属病院（神奈川県） 神奈川県立がんセンター（神奈川県） 横浜南共済病院（神奈川県） 済生会横浜市南部病院（神奈川県） 横浜保土ヶ谷中央病院（神奈川県） 藤沢市民病院（神奈川県） 神奈川県立足柄上病院（神奈川県） 横須賀市立市民病院（神奈川県） 秦野赤十字病院（神奈川県） 藤沢湘南台病院（神奈川県） 以上Yokohama Liver Study Group（YLSG）

Other administrative information
Date of disclosure of the study information	2015 Year 12 Month 04 Day

Related information
URL releasing protocol	None
Publication of results	Published

Result
URL related to results and publications	https://pubmed.ncbi.nlm.nih.gov/33761674/
Number of participants that the trial has enrolled	119
Results	A total of 98.1% of (n=101/103) patients in genotype 1 cohort and 100% (n=16/16) in the genotype 2 cohort achieved SVR12. Based on per-protocol analysis, M2BPGi levels showed a significant decrease (-2.2 cut-off index [COI], P<.0001) at week 48 after treatment initiation. Forty-three patients showed a significant decrease in Fib-4 index (-1.2, P<.0001), and 44 patients showed improvement in LSM (-5.9 kPa, P<.0001).Achievement of SVR after antiviral therapy was associated with fibrosis regression.
Results date posted	2021 Year 03 Month 26 Day
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics	patients with genotype 1 and genotype 2 were given standard treatment of ledipasvir 90 mg/sofosbuvir 400 mg and sofosbuvir 400 mg + 200-1000 mg/day ribavirin, respectively, for 12 weeks
Participant flow	Liver fibrosis was assessed using Mac-2-binding protein glycosylation isomer (M2BPGi) and other fibrosis markers (platelet count, Fib-4 index, liver stiffness measurement [LSM]) in patients who achieved SVR.
Adverse events	"Overall, AEs were observed during the treatment period 46.2% (55/119) in all patients, 43.7% (45/103) in SOF/LDV group, 62.5% (10/16) in SOF/RBV group: anemia, 17 (14.2%); eruption, 11 (9.2%); fatigue, 8 (6.7%); headache, 8 (6.7%); ALT elevation, 5 (4.2%); AST elevation, 3 (2.5%); nasopharyngitis, 3 (2.5%) total bilirubin elevation, 2 (1.7%); and diarrhea, 1 (0.8%) (Table 3). Anemia, an AE of RBV, was frequently seen in the SOF/RBV group. AEs leading to death or treatment discontinuation were not found."
Outcome measures	A total of 98.1% of (n = 101/103) patients in genotype 1 cohort and 100% (n = 16/16) in the genotype 2 cohort achieved SVR12. Based on per-protocol analysis, M2BPGi levels showed a significant decrease (-2.2 cut-off index [COI], P < .0001) at week 48 after treatment initiation. Forty-three patients showed a significant decrease in Fib-4 index (-1.2, P < .0001), and 44 patients showed improvement in LSM (-5.9 kPa, P < .0001).
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Completed
Date of protocol fixation	2015 Year 11 Month 16 Day
Date of IRB	2015 Year 12 Month 02 Day
Anticipated trial start date	2015 Year 12 Month 07 Day
Last follow-up date	2018 Year 05 Month 07 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other

Other related information

Study design: Cohort study Subject recruitment method: Patients who visited Yokohama Liver Study Group (YLSG )-affiliated facilities from December 2015 to November 2016, fulfilled the selection criteria, and provided consent were enrolled in this study. Measurement items: The M2BPGi level, hyaluronic acid level, type IV collagen level, platelet count, FIB-4 index, FibroScan value, and shear wave elastography (SWE) value were assessed.

Management information
Registered date	2015 Year 12 Month 03 Day
Last modified on	2021 Year 11 Month 01 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000023156