search
Back to results

A Randomized,Double-blind, Placebo Controlled, Multicenter Study to Evaluate the Safety and Efficacy of MT2004 Capsule in DILI Subjects

Primary Purpose

Drug-Induced Liver Injury, Cholestatic Liver Injury, Mixed Liver Injury

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
MT2004 Capsule
MT2004 Capsule Placebo
Sponsored by
Xi'An Aolitai Pharmaceutical Technology Co Ltd
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Drug-Induced Liver Injury focused on measuring Drug-Induced Liver Injury

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 1. 18≤ age ≤ 75 years, male or female. 2. When diagnosis of acute DILI, the liver biochemical threshold of patients must meet one of the following criteria: :(1) ALT ≥5 ×ULN;(2) ALP ≥2× ULN;(3) ALT≥3× ULN and TBil ≥2×ULN. 3. ALP ≥2× ULN, and conform to the clinical classification of cholestatic type or mixed type DILI in the Chinese Guidelines for the Diagnosis and Treatment of Drug-induced Liver Injury (2023 edition) (cholestatic type: R value ≤2; Mixed type: 2<R value <5). 4. Excluded other common causes of acute liver injury, such as acute viral hepatitis A, B, C, E, autoimmune hepatitis, biliary tract disease, PBC, etc. (Exclusive diagnostic tests completed in our hospital or other hospitals after this suspected acute DILI event or within 2 months before screening were acceptable) 5. RUCAM causality scale score ≥6 points; If the RUCAM score is between the 3-5 it is necessary to evaluate the causal relationship by three experts according to the evaluation criteria of expert opinions in the Chinese Guidelines for the Diagnosis and Treatment of Drug-induced Liver Injury (2023 edition), and at least two experts determine that the liver injury of the patients are "likely", "very likely" or "definitely" caused by drugs. 6. The serious level of DILI is within level 1-2 based on the Chinese Guidelines for the Diagnosis and Treatment of Drug-induced Liver Injury (2023 edition). 7. The duration of this liver injury is less than 6 months. 8. The female with fertility must have had a negative pregnancy test results before being enrolled, or at least 1 year after pausimenia, or permanent sterilization ≥6 weeks(There should have a recording of hysterectomy, bilateral salpingo-oophorectomy). The female and their male partners with the fertility potential agree to utilize the effective contraceptive methods(the following two methods can be selected: 1. any of the condom, diaphragm, Sponge or Cervical Cap with with Spermicide ). 9. Fully understand the study process of the clinical trial, and provide the signed ICF of joinning the clinical trial. Exclusion Criteria: 1. Acute or chronic liver failure or liver decompensation 2. The history of liver decompensation or portal hypertension history 3. Moderate or above renal insufficiency, creatinine clearance (Ccr) < 60mL/min (according to the MDRD formula). 4. Patients with serious diabetes and had poor control of blood sugar (HbA1c>10%) 5. Serious sysmetic diseases of cardiovascular, respiratory, neurological, urinary, digestive, and for any reason which, in the opinion of the Investigator think the subject is not suitable for participating in the study. 6. The predict survival period < 6 months. 7. Utilization of Perursodeoxycholic acid within 14 days before the treatment. 8. Utilization of S-adenosylmethionine within 1 days before the treatment. 9. The patients must regularly utilize the known strong CYP3A4/3A5 inhibitors such as Clarithromycin, Itraconazole, ketoconazole, Ritonavir, rifampicin, phenytoin, carbamazepine within 1 week before the treatment or for the whole study period. 10. Allergies or intolerances to study drug ingredients 11. Patients are under the gestation, lactation, or patients have the pregnancy planning during the study period and 90 days after the end of the clinical trial 12. Patients are not willing to ban the alcohol during the study period. 13. Patients had joined the other clinical trials within 3 months before the administration. 14. Other conditions that the investigator think the subject is not suitable for participating in the study.

Sites / Locations

  • Shanghai Jiaotong University School of Medicine,Renji HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

MT2004 Capsule

MT2004 Capsule Placebo

Arm Description

The MT2004 Capsule will be orally used twice daily after meal for 12 weeks.

The MT2004 Capsule Placebo will be orally used twice daily after meal for 12 weeks.

Outcomes

Primary Outcome Measures

Primary efficacy endpoint
The efficacy of MT2004 will be evaluated based on the decreasing rate on serum ALP compared to baseline.

Secondary Outcome Measures

Secondary efficacy endpoint
The efficacy of MT2004 will be evaluated based on the decreasing rate on ALP compared to baseline.
Secondary efficacy endpoint
The efficacy of MT2004 will be evaluated based on the percentage of patients whose ALP decreased by more than 15% from baseline.
Secondary efficacy endpoint
The efficacy of MT2004 will be evaluated based on the recovery rate of ALP.
Secondary efficacy endpoint
The efficacy of MT2004 will be evaluated based on the decreasing rate on GGT compared to baseline.
Secondary efficacy endpoint
The efficacy of MT2004 will be evaluated based on the recovery rate of GGT.
Secondary efficacy endpoint
The efficacy of MT2004 will be evaluated based on the decreasing rate on ALT compared to baseline.
Secondary efficacy endpoint
The efficacy of MT2004 will be evaluated based on the recovery rate of ALT.
Secondary efficacy endpoint
The efficacy of MT2004 will be evaluated based on the decreasing rate on AST compared to baseline.
Secondary efficacy endpoint
The efficacy of MT2004 will be evaluated based on the recovery rate of AST.
Secondary efficacy endpoint
The efficacy of MT2004 will be evaluated based on the decreasing rate on TBIL compared to baseline.
Secondary efficacy endpoint
The efficacy of MT2004 will be evaluated based on the decreasing rate on TBA compared to baseline.
Secondary efficacy endpoint
The efficacy of MT2004 will be evaluated based on the area of serum ALP decreasing rate-time curve.
Secondary efficacy endpoint
The efficacy of MT2004 will be evaluated based on the percentage of patients developed to DILI level 3-4 after the administration.

Full Information

First Posted
August 25, 2023
Last Updated
August 25, 2023
Sponsor
Xi'An Aolitai Pharmaceutical Technology Co Ltd
search

1. Study Identification

Unique Protocol Identification Number
NCT06019936
Brief Title
A Randomized,Double-blind, Placebo Controlled, Multicenter Study to Evaluate the Safety and Efficacy of MT2004 Capsule in DILI Subjects
Official Title
A Randomized,Double-blind, Placebo Controlled, Multicenter Study to Evaluate the Safety and Efficacy of MT2004 Capsule in Treatment of Cholestatic and Mixed Drug Induced Liver Injury (DILI)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 10, 2023 (Actual)
Primary Completion Date
August 10, 2025 (Anticipated)
Study Completion Date
October 10, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Xi'An Aolitai Pharmaceutical Technology Co Ltd

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The goal of this randomized, double-blind, placebo controlled, Multicenter Phase II clinical trial is to initially evaluate the Safety and Efficacy of MT2004 Capsule in Cholestatic and Mixed drug induced liver injury (DILI) subjects. The main questions it aims to answer are: The Efficacy of MT2004 Capsule in Cholestatic and Mixed DILI subjects The Safety and Pharmacokinetic characteristic of MT2004 Capsule in Cholestatic and Mixed DILI subjects The mechanism of using MT2004 Capsule on Cholestatic and Mixed DILI subjects
Detailed Description
Xi'An Aolitai Pharmaceutical Technology Co Ltd is developing MT2004, a novel investigational synthetic small molecule farnesoid X receptor (FXR) agonist targeted to the liver. The MT2004 was designed as the prodrug and the metabolites MT2004-met1 of MT2004 will act to the FXR receptor to regulate a series of genes expression. It also plays an important role in the metabolism of bile acids, lipids and sugars. The goal of this randomized, double-blind, placebo controlled, Multicenter Phase II clinical trial is to initially evaluate the Safety and Efficacy of MT2004 Capsule in Cholestatic and Mixed drug induced liver injury (DILI) subjects. The whole study will be divied to three stages including screening period (14 Days before the treatment), treatment period (the participants will be randomized to receive MT2004, or placebo orally (BID), for 12 weeks) and follow-up period. The study aims to recruit total of 80 subjects with Cholestatic and Mixed DILI, in which 12 of subjects will be firstly enrolled and allocated to the MT2004 group (Dose level: 25mg) as well as control group with the proportion of 2:1 by using the stratified randomization method. During the whole study, the adjustment of the subjects amount, the dose level as well as randomization proportion will based on the decesion of Independent Data Monitoring Board (IDMC). The highest dose will not exceed the 50mg BID. The placebo will be used in this study, and the researchers will compare the placebo and test article to see the safety and efficacy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Drug-Induced Liver Injury, Cholestatic Liver Injury, Mixed Liver Injury
Keywords
Drug-Induced Liver Injury

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Masking Description
The study will be double-blinded for MT2004/matching placebo. The subjects and the clinical personnel involved in the collection, monitoring, revision, or evaluation of AEs, or personnel who could have an impact on the outcome of the study will be blinded with respect to the subject's treatment assignment (MT2004 or placebo).Blinding will be maintained until at least the clinical phase of the study is completed.
Allocation
Randomized
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
MT2004 Capsule
Arm Type
Experimental
Arm Description
The MT2004 Capsule will be orally used twice daily after meal for 12 weeks.
Arm Title
MT2004 Capsule Placebo
Arm Type
Placebo Comparator
Arm Description
The MT2004 Capsule Placebo will be orally used twice daily after meal for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
MT2004 Capsule
Other Intervention Name(s)
MT2004
Intervention Description
The stratified randomization method will be used in this study. In treatment period, the participants will orally receive the MT2004 (BID) for 12 weeks with the dose level of 25mg. The adjustment of the dose level will base on the decesion of Independent Data Monitoring Board (IDMC). The highest dose will not exceed the 50mg BID.
Intervention Type
Drug
Intervention Name(s)
MT2004 Capsule Placebo
Intervention Description
The stratified randomization method will be used in this study. In treatment period, the participants will orally receive the MT2004 Capsule Placebo (BID) for 12 weeks with the dose level of 25mg. The adjustment of the dose level will base on the decesion of Independent Data Monitoring Board (IDMC). The highest dose will not exceed the 50mg BID.
Primary Outcome Measure Information:
Title
Primary efficacy endpoint
Description
The efficacy of MT2004 will be evaluated based on the decreasing rate on serum ALP compared to baseline.
Time Frame
On the week 4 after the administration
Secondary Outcome Measure Information:
Title
Secondary efficacy endpoint
Description
The efficacy of MT2004 will be evaluated based on the decreasing rate on ALP compared to baseline.
Time Frame
On the week 2,8,12 after the administration and the week 4 follow-up period
Title
Secondary efficacy endpoint
Description
The efficacy of MT2004 will be evaluated based on the percentage of patients whose ALP decreased by more than 15% from baseline.
Time Frame
On the week 2,4,8,12 after the administration and the week 4 follow-up period
Title
Secondary efficacy endpoint
Description
The efficacy of MT2004 will be evaluated based on the recovery rate of ALP.
Time Frame
On the week 2,4,8,12 after the administration and the week 4 follow-up period
Title
Secondary efficacy endpoint
Description
The efficacy of MT2004 will be evaluated based on the decreasing rate on GGT compared to baseline.
Time Frame
On the week 2,4,8,12 after the administration and the week 4 follow-up period
Title
Secondary efficacy endpoint
Description
The efficacy of MT2004 will be evaluated based on the recovery rate of GGT.
Time Frame
On the week 2,4,8,12 after the administration and the week 4 follow-up period
Title
Secondary efficacy endpoint
Description
The efficacy of MT2004 will be evaluated based on the decreasing rate on ALT compared to baseline.
Time Frame
On the week 2,4,8,12 after the administration and the week 4 follow-up period
Title
Secondary efficacy endpoint
Description
The efficacy of MT2004 will be evaluated based on the recovery rate of ALT.
Time Frame
On the week 2,4,8,12 after the administration and the week 4 follow-up period
Title
Secondary efficacy endpoint
Description
The efficacy of MT2004 will be evaluated based on the decreasing rate on AST compared to baseline.
Time Frame
On the week 2,4,8,12 after the administration and the week 4 follow-up period
Title
Secondary efficacy endpoint
Description
The efficacy of MT2004 will be evaluated based on the recovery rate of AST.
Time Frame
On the week 2,4,8,12 after the administration and the week 4 follow-up period
Title
Secondary efficacy endpoint
Description
The efficacy of MT2004 will be evaluated based on the decreasing rate on TBIL compared to baseline.
Time Frame
On the week 2,4,8,12 after the administration and the week 4 follow-up period
Title
Secondary efficacy endpoint
Description
The efficacy of MT2004 will be evaluated based on the decreasing rate on TBA compared to baseline.
Time Frame
On the week 2,4,8,12 after the administration and the week 4 follow-up period
Title
Secondary efficacy endpoint
Description
The efficacy of MT2004 will be evaluated based on the area of serum ALP decreasing rate-time curve.
Time Frame
On the week 2,4,8,12 after the administration
Title
Secondary efficacy endpoint
Description
The efficacy of MT2004 will be evaluated based on the percentage of patients developed to DILI level 3-4 after the administration.
Time Frame
On the week 2,4,8,12 after the administration and the week 4 follow-up period
Other Pre-specified Outcome Measures:
Title
Safety endpoint
Description
Adverse Events(AEs) will be recorded and evaluated for their seriousness, severity, and relationship to the study drug.
Time Frame
From the date of screening until the date of last follow-up visit or early termination and end of study, assessed up to 12 weeks.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 1. 18≤ age ≤ 75 years, male or female. 2. When diagnosis of acute DILI, the liver biochemical threshold of patients must meet one of the following criteria: :(1) ALT ≥5 ×ULN;(2) ALP ≥2× ULN;(3) ALT≥3× ULN and TBil ≥2×ULN. 3. ALP ≥2× ULN, and conform to the clinical classification of cholestatic type or mixed type DILI in the Chinese Guidelines for the Diagnosis and Treatment of Drug-induced Liver Injury (2023 edition) (cholestatic type: R value ≤2; Mixed type: 2<R value <5). 4. Excluded other common causes of acute liver injury, such as acute viral hepatitis A, B, C, E, autoimmune hepatitis, biliary tract disease, PBC, etc. (Exclusive diagnostic tests completed in our hospital or other hospitals after this suspected acute DILI event or within 2 months before screening were acceptable) 5. RUCAM causality scale score ≥6 points; If the RUCAM score is between the 3-5 it is necessary to evaluate the causal relationship by three experts according to the evaluation criteria of expert opinions in the Chinese Guidelines for the Diagnosis and Treatment of Drug-induced Liver Injury (2023 edition), and at least two experts determine that the liver injury of the patients are "likely", "very likely" or "definitely" caused by drugs. 6. The serious level of DILI is within level 1-2 based on the Chinese Guidelines for the Diagnosis and Treatment of Drug-induced Liver Injury (2023 edition). 7. The duration of this liver injury is less than 6 months. 8. The female with fertility must have had a negative pregnancy test results before being enrolled, or at least 1 year after pausimenia, or permanent sterilization ≥6 weeks(There should have a recording of hysterectomy, bilateral salpingo-oophorectomy). The female and their male partners with the fertility potential agree to utilize the effective contraceptive methods(the following two methods can be selected: 1. any of the condom, diaphragm, Sponge or Cervical Cap with with Spermicide ). 9. Fully understand the study process of the clinical trial, and provide the signed ICF of joinning the clinical trial. Exclusion Criteria: 1. Acute or chronic liver failure or liver decompensation 2. The history of liver decompensation or portal hypertension history 3. Moderate or above renal insufficiency, creatinine clearance (Ccr) < 60mL/min (according to the MDRD formula). 4. Patients with serious diabetes and had poor control of blood sugar (HbA1c>10%) 5. Serious sysmetic diseases of cardiovascular, respiratory, neurological, urinary, digestive, and for any reason which, in the opinion of the Investigator think the subject is not suitable for participating in the study. 6. The predict survival period < 6 months. 7. Utilization of Perursodeoxycholic acid within 14 days before the treatment. 8. Utilization of S-adenosylmethionine within 1 days before the treatment. 9. The patients must regularly utilize the known strong CYP3A4/3A5 inhibitors such as Clarithromycin, Itraconazole, ketoconazole, Ritonavir, rifampicin, phenytoin, carbamazepine within 1 week before the treatment or for the whole study period. 10. Allergies or intolerances to study drug ingredients 11. Patients are under the gestation, lactation, or patients have the pregnancy planning during the study period and 90 days after the end of the clinical trial 12. Patients are not willing to ban the alcohol during the study period. 13. Patients had joined the other clinical trials within 3 months before the administration. 14. Other conditions that the investigator think the subject is not suitable for participating in the study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
LanLan Song, Master
Phone
+8615929300901
Email
songlanlan@micot.cn
First Name & Middle Initial & Last Name or Official Title & Degree
DeChuang Yuan, Master
Email
yuandechuang@micot.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
YiMin Mao, Master
Organizational Affiliation
Shanghai Jiaotong University School of Medicine,Renji Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Shanghai Jiaotong University School of Medicine,Renji Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200001
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
YiMin Mao, Master
Phone
+8613003175438
Email
maoym@163.com
First Name & Middle Initial & Last Name & Degree
YiMin Mao, Master

12. IPD Sharing Statement

Learn more about this trial

A Randomized,Double-blind, Placebo Controlled, Multicenter Study to Evaluate the Safety and Efficacy of MT2004 Capsule in DILI Subjects

We'll reach out to this number within 24 hrs