UMIN-CTR Clinical Trial

Public title

Investigation of the efficacy and safety of ledipasvir and sofosbuvir therapy for Genotype 1 Hepatitis C Virus infection in patients with decompensated cirrhosis

Acronym

LDF/SOF for decompensated cirrhosis

Scientific Title

Investigation of the efficacy and safety of ledipasvir and sofosbuvir therapy for Genotype 1 Hepatitis C Virus infection in patients with decompensated cirrhosis

Scientific Title:Acronym

LDF/SOF for decompensated cirrhosis

Region

Japan

Condition

Decompensated cirrhosis by Genotype 1 Hepatitis C Virus infection

Classification by specialty

Hepato-biliary-pancreatic medicine

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

Investigation of the efficacy and safety of ledipasvir and sofosbuvir therapy for Genotype 1 Hepatitis C Virus infection in patients with decompensated cirrhosis

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

Serious adverse events occurrence rate

Key secondary outcomes

sustained virological response

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Ledipasvir(90mg)/sofosbuvir(400mg) for 12 weeks

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

Subjects must meet all of the following inclusion criteria to be eligible for participation in this study.
1)CPT class B or C cirrhosis with chronic infection of HCV genotype 1
2)Age > 20 years at screening
3)Performance status (ECOG) 0, 1 or 2
4)eGFR > 30 mL/min/1.73m2
5)Able to understand and sign the Informed Consent Document

Key exclusion criteria

1)
a)Clinically significant illness or currently under evaluation for a potentially clinically significant illness or any other major medical disorder that may interfere with subject treatment, assessment or compliance with the protocol.
b)Gastrointestinal disorder or postoperative condition that could interferer with the absorption of the study drugs
c)Difficulty with blood collection and/or poor venous access for the purposes of phlebotomy.
d)Significant pulmonary disease
e)Unstable cardiac disease or significant cardiac event within one year prior to Screening
f)Psychiatric hospitalization, suicide attempt, and/or a period of disability as a result of their psychiatric illness within the last 2 years prior to Screening
g)Significant drug allergy
h)Hepatopulmonary syndrome
i)Hepatorenal syndrome
2)Screening ECG with clinically significant abnormalities
3)Pregnant or nursing female or male with pregnant female partner
4)Women who wish to become pregnant or males with female partners who wish to become pregnant during study treatment or 30 days after the last dose LDV/SOF
5)Active spontaneous bacterial peritonitis at Screening
6)Evidence of fibrosing cholestatic hepatitis
7)Life threatening SAE during Screening
8)Active variceal bleeding within 6 months of Screening
9)Subjects with any of the following laboratory parameters at Screening:
a)Hemoglobin (Hb) < 10g/dL
b)Platelets < 50000/mm3
c)Neutrophils < 1000/mm3
d)ALT, AST, or alkaline phosphatase > 10 x ULN
e)Sodium < 125 mEq/L
f)Total bilirubin > 10 mg/dL
g)eGFR < 30 ml/min/1.73m2
10)Donation or loss of more than 400mL o blood within 2 months prior to Day 1
11)Any prohibited medications as described below
Carbamazepine, Phenytoin, Rifampicin, St John Wort
12)Known hypersensitivity to ledipasvir, sofosbuvir, or the metabolities or formulation excipients
13)Others judged as being inappropriate for the subjects of the study by investigators.

Target sample size

15

Name of lead principal investigator

1st name	Tetsuo
Middle name
Last name	Takehara

Organization

Osaka University Graduate School of Medicine

Division name

Department of Gastroenterology and Hepatology

Zip code

5650871

Address

2-2 Yamadaoka, Suita, Osaka, Japan

TEL

06-6879-3621

Email

takehara@gh.med.osaka-u.ac.jp

Name of contact person

1st name	Ryotaro
Middle name
Last name	Sakamori

Organization

Osaka University Graduate School of Medicine

Division name

Department of Gastroenterology and Hepatology

Zip code

5650871

Address

2-2 Yamadaoka, Suita, Osaka, Japan

TEL

06-6879-3621

Homepage URL

Email

sakamori@gh.med.osaka-u.ac.jp

Institute

Osaka University Graduate School of Medicine

Institute

Department

Personal name

Organization

Osaka University Graduate School of Medicine
Funding from patient

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Osaka University Clinical Research Review Committee

Address

2-2 Yamadaoka, Suita, Osaka, Japan

Tel

06-6210-8296

Email

rinri@hp-crc.med.osaka-u.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2018

Year

05

Month

01

Day

URL releasing protocol

https://jrct.niph.go.jp/latest-detail/jRCTs051180003

Publication of results

Published

URL related to results and publications

https://jrct.niph.go.jp/latest-detail/jRCTs051180003

Number of participants that the trial has enrolled

1

Results

One patient was enrolled, and protocol treatment was completed in one case. Therefore, the number of cases subject to the primary efficacy endpoint (all treatments) and the secondary endpoint (all eligible cases) was one.

Results date posted

2020

Year

08

Month

12

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

2021

Year

03

Month

01

Day

Baseline Characteristics

Decompensated cirrhosis by Genotype 1 Hepatitis C Virus infection
(one patient enrolled, 76 years old female)

Participant flow

The elimination rate of hepatitis C virus at 12 weeks after the end of treatment (Day 169), which is the primary endpoint of efficacy, was 100% (1 of 1 case), and the primary endpoint of efficacy was achieved. Hepatitis C virus elimination was obtained 12 weeks after the end of treatment (Day 169), and viral elimination was continuously obtained 24 weeks after the end of treatment. Regarding the secondary efficacy endpoint, the Child-Pugh score improved from B (7 points) to A (6 points), improving the liver function indicated by Child-Pugh score, while no significant change of MELD score was observed until 12 weeks after completion. An increase in MELD score was observed 24 weeks after the end of treatment, but this was accompanied by a temporary increase in creatinine, and it was judged that hepatic function was not deteriorated. Based on the above, it is judged comprehensively that liver function has improved. The carcinogenic inhibitory effect was not judged because it was a single case, but in this case, no liver carcinogenesis was observed within the observation period, and a decrease in PIVKA-II, a tumor marker for liver cancer, was observed. There was a possibility that liver fibrosis markers decreased at the time of subsequent observation compared with the start of treatment in all 4 factors, and the possibility of improvement in fibrosis was obtained. From the above, it is considered that the effectiveness was recognized although it was an evaluation in one example.

Adverse events

The primary safety endpoint, rate of serious adverse events caused by this study drug from the start of treatment to 12 weeks after the end of treatment was 0% (0 of 1 case).
Regarding adverse events, a secondary endpoint of safety, Shortness of breath (exertional dyspnea) was observed, but it was non-serious and considered not to have a direct causal relationship to the study drug. Other safety secondary endpoints: early death rate was 0% (0 cases), treatment-related death rate was 0% (0 cases), protocol treatment completion rate was 100% (1 of 1 case) and it was judged that safety of this study was shown although it was an evaluation in only 1 case.

Outcome measures

In this study, Epcrusa combination tablet (Sofosbuvir / Velpatasvir combination tablet) was approved for hepatitis C decompensated cirrhosis after the start of the study, so this study was discontinued in 1 patient enrolled. Although the protocol treatment was completed in one case, it was considered that efficacy and safety were confirmed by confirming the primary and secondary endpoints of efficacy and safety.

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2018

Year

02

Month

13

Day

Date of IRB

2018

Year

06

Month

06

Day

Anticipated trial start date

2018

Year

08

Month

07

Day

Last follow-up date

2019

Year

07

Month

20

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2018

Year

02

Month

09

Day

Last modified on

2021

Year

02

Month

11

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000035667