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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Liver Cirrhosis

Intervention / Treatment
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* Drug: Foscenvivint


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria Hemophilia patients with liver cirrhosis caused by HIV/HCV co-infection that fall under the following 1) and 2): 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). 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: Liver stiffness measurement by FibroScan is >= 12.5 kPa (Fibrosis stage F4) at screening. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Foscenvivint<br>Foscenvivint 280 mg/m2, twice a week for 24 weeks | Drug: Foscenvivint<br>* Administered by intravenous (IV) infusion over 3-4 hours<br>* Other names: PRI-724 (former name);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| ALBI score | Change from baseline in ALBI score at 12 and 28 weeks after administration. | Baseline to 12 and 28 weeks after administration | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| PT% | Change from baseline in PT% at 12, 24 and 28 weeks after administration. | Baseline to 12, 24 and 28 weeks after administration | 
| 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 | 
| 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 √ ALT [U/L] ) | Baseline to 12, 24 and 28 weeks after administration | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liver Cirrhosis, Hemophilia, HIV/HCV co-infection