UMIN-CTR Clinical Trial

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

chronic hepatitis C

Classification by specialty

Hepato-biliary-pancreatic medicine

Classification by malignancy

Others

Genomic information

NO

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

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

Study type

Observational

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

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

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

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

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

Institute

Yokohama City University Medical Center

Institute

Department

Personal name

Organization

Gilead Sciences K.K

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

United States of America

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

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）

Date of disclosure of the study information

2015

Year

12

Month

04

Day

URL releasing protocol

None

Publication of results

Published

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

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 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.

Registered date

2015

Year

12

Month

03

Day

Last modified on

2021

Year

11

Month

01

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000023156