A Phase 2 Trial of Foscenvivint in Liver Cirrhosis Patients Caused by HIV/HCV Co-infection With Hemophilia (OP-724-H201)

Liver Cirrhosis Clinical Trial

Official title:

A Multi-center, Single-arm, Open-label Phase 2 Trial of Foscenvivint in Liver Cirrhosis Patients Caused by HIV/HCV Co-infection With Hemophilia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06144086
• Other study ID #: OP-724-H201
• Secondary ID: jRCT2031230461
• Status: Recruiting
• Phase: Phase 2
• Start date: May 8, 2024
• Est. completion date: June 30, 2025

Study information

• Verified date: May 2024
• Source: Komagome Hospital
• Contact: Kiminori Kimura, MD
• Phone: +81-3-3823-2101
• Email: kiminori_kimura[@]tmhp.jp
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a phase 2 trial of foscenvivint in liver cirrhosis patients caused by HIV/HCV co-infection with hemophilia to evaluate the efficacy, safety and pharmacokinetics.

Description:

This is designed a multi-center, single-arm, open-label trial of foscenvivint administered intravenously twice a week for 24 weeks. A follow up visit will be conducted 4 weeks after the last administration.

Liver cirrhosis patients due to co-infection of HIV and HCV with hemophilia who have a Child-Pugh classification of A or B are included.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 6
• Est. completion date: June 30, 2025
• Est. primary completion date: March 31, 2025
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 74 Years

Eligibility

Key Inclusion Criteria

• Hemophilia patients with liver cirrhosis caused by HIV/HCV co-infection that fall under the following 1) and 2):

1. Serum HIV-RNA positive or HIV antibody positive patients (maintaining HIV-RNA < 200 copies/mL and CD4 positive T lymphocyte count >= 200 cells/µL at screening).

2. Regarding HCV, patients who had passed >= 12 months after achieving SVR at registration.

• Patients with Child-Pugh classification A or B (Child-Pugh score 5-9).

• Patients who meet at least one of 1) to 2) for diagnosis of liver cirrhosis:

1. Liver stiffness measurement by FibroScan is >= 12.5 kPa (Fibrosis stage F4) at screening.

2. Abdominal CT scan shows changes in liver shape and/or portal hypertension.

• Patients with Performance Status 0-2.

Key Exclusion Criteria

• Patients with liver cirrhosis of which cause is not HCV or unknown.

• Patients with esophageal gastric varices judged to require treatment by endoscopic examinations at screening.

• Patients with complication or history of malignant tumor (within 3 years before registration).

• Patients who have undergone liver transplantation or other organ transplantation (including bone marrow transplantation).

• Patients with active AIDS-indicator disease that require treatment.

Related Conditions & MeSH terms

• Coinfection
• Fibrosis
• Hemophilia A
• Infections
• Liver Cirrhosis

Intervention

Drug:
• Foscenvivint
Administered by intravenous (IV) infusion over 3-4 hours

Locations

Country	Name	City	State
Japan	Tokyo Metropolitan Komagome Hospital	Bunkyo-Ku	Tokyo
Japan	National Hospital Organization Osaka National Hospital	Osaka
Japan	Hokkaido University Hospital	Sapporo	Hokkaido

Sponsors (2)

Lead Sponsor	Collaborator
Kiminori Kimura, MD	Japan Agency for Medical Research and Development

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ALBI score	Change from baseline in ALBI score at 24 weeks after administration.; ALBI score = (log10 bilirubin [mg/dL] x 17.1) x 0.66 + (albumin [g/dL] x 10 x -0.085)	Baseline to 24 weeks after administration
Secondary	Child-Pugh score	Change from baseline in Child-Pugh score at 12, 24 and 28 weeks after administration.; Child-Pugh score is determined by scoring the following five clinical measures.; Encephalopathy: None = 1 point, Grade 1 and 2 = 2 points, Grade 3 and 4 = 3 points; Ascites: None = 1 point, slight = 2 points, moderate = 3 points; Bilirubin: < 2 mg/dL = 1 point, 2 to 3 mg/dL = 2 points, > 3 mg/dL = 3 points; Albumin: > 3.5 g/dL = 1 point, 2.8 to 3.5 g/dL = 2 points, < 2.8 g/dL = 3 points; Prothrombin Time (%): > 70% = 1 point, 40 to 70% = 2 points, < 40% = 3 points	Baseline to 12, 24 and 28 weeks after administration
Secondary	ALBI score	Change from baseline in ALBI score at 12 and 28 weeks after administration.	Baseline to 12 and 28 weeks after administration
Secondary	Liver stiffness measurement by FibroScan	Change from baseline in Liver stiffness measurement by FibroScan at 12 and 24 weeks after administration.	Baseline to 12 and 24 weeks after administration
Secondary	Serum fibrosis markers	Change from baseline in Serum fibrosis markers at 12 and 24 weeks after administration.	Baseline to 12 and 24 weeks after administration
Secondary	Serum albumin	Change from baseline in serum albumin at 12, 24 and 28 weeks after administration.	Baseline to 12, 24 and 28 weeks after administration
Secondary	Serum bilirubin	Change from baseline in serum bilirubin at 12, 24 and 28 weeks after administration.	Baseline to 12, 24 and 28 weeks after administration
Secondary	PT%	Change from baseline in PT% at 12, 24 and 28 weeks after administration.	Baseline to 12, 24 and 28 weeks after administration
Secondary	MELD score	Change from baseline in MELD score at 12, 24 and 28 weeks after administration.; The Model for End-Stage Liver Disease (MELD) is a scoring system for assessing the severity of chronic liver disease and uses the subject's values for total bilirubin, serum creatinine, and the international normalized ratio (INR) for prothrombin time to predict survival. The higher the score, the more serious the subject's disease. MELD is calculated according to the following formula: MELD score = 3.78 x ln(serum bilirubin [mg/dL]) + 11.2 x ln(PT-INR) + 9.57 x ln(serum creatinine [mg/dL]) + 6.43	Baseline to 12, 24 and 28 weeks after administration
Secondary	FIB-4 index	Change from baseline in FIB-4 index at 12, 24 and 28 weeks after administration.; FIB-4 index = (Age [years] x AST [U/L]) / (Platelet Count [10*9/L] x v ALT [U/L] )	Baseline to 12, 24 and 28 weeks after administration
Secondary	mALBI grade	Percentage of subjects who achieved >= 1 stage improvement in mALBI grade from baseline at 12, 24 and 28 weeks after administration.; Based on ALBI score, mALBI grade is classified into Grade 1 to 3 shown below.; mALBI grade: Grade 1: <=-2.60; Grade 2a: >-2.60 to <-2.27; Grade 2b: >=-2.27 to -1.39; Grade 3: >-1.39	Baseline to 12, 24 and 28 weeks after administration
Secondary	Achievement in Child-Pugh classification	Percentage of subjects who changed from grade B at baseline to grade A at 12, 24 and 28 weeks after administration in Child-Pugh classification.; Based on the total points in Child-Pugh score (scale range 5-15 points, the severity increases sequentially from 5 to 15 points), the severity of the disease is classified into Grade A to C shown below.; Child-Pugh classification: Grade A: 5 to 6 points -> Compensated cirrhosis; Grade B: 7 to 9 points -> Decompensated cirrhosis; Grade C: 10 to 15 points -> Decompensated cirrhosis	Baseline to 12, 24 and 28 weeks after administration
Secondary	Achievement in Child-Pugh score	Percentage of subjects who achieved >= 2 points improvement from baseline in Child-Pugh score at 12, 24 and 28 weeks after administration.	Baseline to 12, 24 and 28 weeks after administration
Secondary	Achievement in Child-Pugh classification and score	Percentage of subjects who changed from grade B to grade A in Child-Pugh classification and achieved >= 2 points improvement in Child-Pugh score from baseline at 12, 24 and 28 weeks after administration.	Baseline to 12, 24 and 28 weeks after administration