Overview

F573 for Injection for the Treatment of Liver Injury/Failure

Status:
Not yet recruiting

Trial end date:
2026-03-31

Target enrollment:
0

Participant gender:
All

Summary

This study was a randomized, double-blind, placebo-controlled PhaseⅡ clinical trial . The main objective of this study was to confirm the efficacy and safety of F573 for injection in the treatment of liver injury/failure.

Phase:

Phase 2

Accepts Healthy Volunteers?

Details

Lead Sponsor:

Beijing Continent Pharmaceutical Co, Ltd.

Criteria

Inclusion Criteria:The first stage:

Subjects who meet all of the following criteria will be enrolled in the study:

1. Age is 18 and 60 years old, gender is unlimited;

2. Clinically diagnosed as hepatocyte injury type DILI patients or CHB patients infected
with HBV for more than 6 months, the subject population is defined as follows:

- Grade 1/2 DILI patients: refer to the "Guidelines for the Diagnosis and Treatment
of Drug-induced Liver Injury, 2015 edition", Drug-induced liver injury refers to
the liver injury induced by various kinds of prescribed or over-the-counter
chemical drugs, biological agents, traditional Chinese medicine, natural drugs,
health care products, dietary supplements and their metabolites and even
auxiliary materials; (1) The patient presented with elevated serum ALT, ALP, GGT,
and TBil; (2) Liver ultrasound has no obvious changes or only mild enlargement;
(3) After tracing the history of suspected drug application and other causes of
liver injury, necessarily, the patients take other measures such as liver biopsy
to confirm the diagnosis of DILI; (4) Clinical classification is hepatocyte
injury type (defined as ALT ≥3 ×ULN and R value ≥5, R value = [ALT / ULN]÷ [ALP /
ULN]); (5) Severity level is level 1 or level 2 (where level 1 is defined as:
TBil < 2.5 ×ULN and INR <1.5, Accompanied with or without accompanying clinical
symptoms; Level 2 is defined as: TBil ≥2.5×ULN, Or, although without elevated
TBil but with INR ≥1.5, Severe clinical symptoms).

- CHB patients: refer to the "Chronic hepatitis B Prevention Guidelines (2019
edition)", screening period can provide etiological evidence (HBsAg positive and
/ or HBV DNA positive) or clinical or pathological evidence (liver tissue biopsy
results) that hepatitis B virus infection for more than 6 months;

3. Subject serum ALT: 2~10 × upper limit of normal value (ULN), TBil: < 5×ULN;

4. DILI patients: the abnormal duration of liver biochemical indexes [ALT, AST, ALP, γ
-glutamyl-transpeptidase (GGT), TBil, albumin, and prothrombin time] is not more than
90 days;

5. Subjects (including their partners) are willing to voluntarily take effective
contraception within 6 months from the screening period until the last trial drug was
given;

6. Subjects can sign the informed consent and comply with the requirements of the
protocol; If the subject cannot sign the informed consent, it shall be signed by the
legal guardian or witness who required by regulations.

(2)The second stage:

Subjects who meet all of the following criteria will be enrolled in the study:

1. Age is 18 and 60 years old, and gender is unlimited;

2. Patients with a clinical diagnosis of hepatocellular injury-type DILI or patients with
HBV infection for more than 6 months, the subject population is defined as follows:

- Grade 2 / 3 DILI patients: refer to the Guidelines for the Diagnosis and
Treatment of Drug-induced Liver Injury (2015 edition). Drug-induced liver injury
refers to the liver injury induced by various kinds of prescribed or
over-the-counter chemical drugs, biological agents, traditional Chinese medicine,
natural drugs, health care products, dietary supplements and their metabolites
and even auxiliary materials; (1) The patient presented with elevated serum ALT,
ALP, GGT, and TBil; (2) Liver ultrasound has no obvious changes or only mild
enlargement; (3) After tracing the history of suspected drug application and
other causes of liver injury, necessarily, the patients take other measures such
as liver biopsy to confirm the diagnosis of DILI; (4) Clinical classification is
the hepatocyte injury type (defined as ALT ≥3×ULN with an R value ≥5.0, R value =
[ALT / ULN]÷ [ALP / ULN]); (5) The Severity level is Level 2 or Level 3 (where
Level 2 is defined as: TBil ≥2.5×ULN, Or, although without elevated TBil but with
INR ≥1.5, Clinical symptoms are aggravated; Level 3 is defined as a TBil ≥5×ULN,
With or without an INR ≥1.5, Clinical symptoms worsen to require
hospitalization).

- CHB patients: refer to the "Chronic hepatitis B Prevention Guidelines (2019
edition)", screening period can provide etiological evidence (HBsAg positive and
/ or HBV DNA positive) or clinical or pathological evidence (liver tissue biopsy
results) that hepatitis B virus infection for more than 6 months;

3. Subject serum ALT: 5~20 × upper limit of normal value (ULN), TBil: <10 × ULN;

4. DILI patients: the abnormal duration of liver biochemical indexes [ALT, AST, ALP, γ
-glutamyl-transpeptidase (GGT), TBil, albumin, and prothrombin time] is not more than
90 days;

5. Subjects (including their partners) are willing to voluntarily take effective
contraception within 6 months from the screening period until the last trial drug was
given;

6. Subjects can sign the informed consent and comply with the requirements of the
protocol; If the subject cannot sign the informed consent, it shall be signed by the
legal guardian or witness who required by regulations.

The third stage:

1. Age is 18 and 70 years old, gender is unlimited;

2. Referring to the "Guidelines for the Diagnosis and Treatment of Liver Failure (2018
edition)" for patients diagnosed with Acute on chronic Liver Failure , TBil ≥5×ULN, 4
weeks with hepatic encephalopathy (grade 1-2) or ascites (grade 1-2) before screening
period, and 5≤ AARC score≤10 (AARC rating of grade I-II);

3. Subjects (including their partners) were willing to voluntarily take effective
contraception within 6 months from the screening period until the last trial drug was
given.

4. Subjects can sign the informed consent and comply with the requirements of the
protocol; If the subject cannot sign the informed consent, it shall be signed by the
legal guardian or witness who required by regulations.

-

Exclusion Criteria:

The first stage:

Subjects meeting one of the following conditions will not be included in the trial:

1. For DILI and CHB population, mixed with other liver factors;

2. Previous diagnosis of cirrhosis or the liver hardness determination in the screening
time (LSM)≥9.0 kPa;

3. Severe severe or life-threatening heart, lung, brain, kidney, gastrointestinal and
systemic diseases, patients with malignant tumors;

4. The following laboratory inspection values or inspection values are abnormal:

1. Blood routine: Platelet (PLT) < 75×109/L , Hemoglobin (HGB) < 90 g / L;

2. Prothrombin activity was < 40%, and prothrombin time (PT) was prolonged for > 5s;

3. Left ventricular ejection fraction (LVEF) was <50%;

5. Allergic or intolerant to trial drugs, or allergic constitution;

6. Subjects were unable to express their own complaints, such as psychosis and severe
neurosis;

7. Poor compliance and they cannot collaborate;

8. Pregnant women, lactating women, or women of childbearing age preparing to conceive;

9. Participating in other clinical trials within 3 months;

10. Patients who have used ursodeoxycholic acid other than adenosine methionine within 3
days before randomization;

11. The investigator considered any circumstances unsuitable for inclusion.

The second stage:

Subjects meeting one of the following conditions will not be included in the trial:

1. For DILI and CHB population, mixed with other liver factors;

2. Previous diagnosis of cirrhosis or the liver hardness determination in the screening
time (LSM)≥9.0 kPa;

3. Severe severe or life-threatening heart, lung, brain, kidney, gastrointestinal and
systemic diseases, patients with malignant tumors;

4. The following laboratory inspection values or inspection values are abnormal:

1. Blood routine: Platelet (PLT) < 75×109/L , Hemoglobin (HGB) < 90 g / L;

2. Prothrombin activity was < 40%, and prothrombin time (PT) was prolonged for > 5s;

3. Left ventricular ejection fraction (LVEF) was < 50%;

5. Allergic or intolerant to trial drugs, or allergic constitution;

6. Subjects were unable to express their own complaints, such as psychosis and severe
neurosis;

7. Poor compliance and they cannot collaborate;

8. Pregnant women, lactating women, or women of childbearing age preparing to conceive;

9. Participating in other clinical trials within 3 months;

10. Patients who have used ursodeoxycholic acid other than adenosine methionine within 3
days before randomization;

11. The investigator considered any circumstances unsuitable for inclusion.

The third stage:

Subjects meeting one of the following conditions will not be included in the trial:

1. Those who have completed the liver transplantation, or plan to do it within 1 month;

2. Severe grade 3 ascites or refractory ascites;

3. Patients with associated grade 3 hepatic encephalopathy;

4. Those who had received artificial liver treatment within 1 week prior to screening
period;

5. Patients with serious basic diseases, such as respiratory system, digestive system,
circulatory system, endocrine system and other diseases and malignant tumors, and
serious infected persons with uncontrollable drugs;

6. The results of gastroscopy or imaging (abdominal B ultrasound, CT or MRI) within 1
month before the screening period or during the screening period, that indicate the
risk of severe varicose veins with bleeding;

7. The following acute kidney injury (AKI) patients are defined as meeting one of the
following conditions:

1. Serum creatinine (Scr) was increased by 26.5 μmol/L (0.3 mg/dL, 1 mg/dL=88.4 μ
mol / L) within 48 hous;

2. the Scr increased by more than 1.5 times or more than the base value within 7
days ;

3. Urinary volume was decreased (<0.5 ml/kg / h) and lasted for more than 6 hours;

8. Allergic or intolerant to trial drugs, or allergic constitution;

9. Subjects were unable to express their own complaints, such as psychosis and severe
neurosis;

10. Poor compliance and they cannot collaborate;

11. Pregnant women, lactating women, or women of childbearing age preparing to conceive;

12. Participating in other clinical trials within 3 months;

13. The investigator considered any circumstances unsuitable for inclusion. -