A Phase 2 Trial of Foscenvivint in Liver Cirrhosis Patients Caused by HIV/HCV Co-infection With Hemophilia (OP-724-H201)
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Foscenvivint Foscenvivint 280 mg/m2, twice a week for 24 weeks |
Drug: Foscenvivint
Administered by intravenous (IV) infusion over 3-4 hours
Other Names:
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Outcome Measures
Primary Outcome Measures
- ALBI score [Baseline to 24 weeks after administration]
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)
Secondary Outcome Measures
- Child-Pugh score [Baseline to 12, 24 and 28 weeks after administration]
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
- ALBI score [Baseline to 12 and 28 weeks after administration]
Change from baseline in ALBI score at 12 and 28 weeks after administration.
- Liver stiffness measurement by FibroScan [Baseline to 12 and 24 weeks after administration]
Change from baseline in Liver stiffness measurement by FibroScan at 12 and 24 weeks after administration.
- Serum fibrosis markers [Baseline to 12 and 24 weeks after administration]
Change from baseline in Serum fibrosis markers at 12 and 24 weeks after administration.
- Serum albumin [Baseline to 12, 24 and 28 weeks after administration]
Change from baseline in serum albumin at 12, 24 and 28 weeks after administration.
- Serum bilirubin [Baseline to 12, 24 and 28 weeks after administration]
Change from baseline in serum bilirubin at 12, 24 and 28 weeks after administration.
- PT% [Baseline to 12, 24 and 28 weeks after administration]
Change from baseline in PT% at 12, 24 and 28 weeks after administration.
- MELD score [Baseline to 12, 24 and 28 weeks after administration]
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
- FIB-4 index [Baseline to 12, 24 and 28 weeks after administration]
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] )
- mALBI grade [Baseline to 12, 24 and 28 weeks after administration]
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
- Achievement in Child-Pugh classification [Baseline to 12, 24 and 28 weeks after administration]
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
- Achievement in Child-Pugh score [Baseline to 12, 24 and 28 weeks after administration]
Percentage of subjects who achieved >= 2 points improvement from baseline in Child-Pugh score at 12, 24 and 28 weeks after administration.
- Achievement in Child-Pugh classification and score [Baseline to 12, 24 and 28 weeks after administration]
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.
Eligibility Criteria
Criteria
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).
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Patients who meet at least one of 1) to 2) for diagnosis of liver cirrhosis:
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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
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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.
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Patients with complication or history of malignant tumor (within 3 years before registration).
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Patients who have undergone liver transplantation or other organ transplantation (including bone marrow transplantation).
-
Patients with active AIDS-indicator disease that require treatment.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Tokyo Metropolitan Komagome Hospital | Bunkyo-Ku | Tokyo | Japan | 113-8677 |
Sponsors and Collaborators
- Kiminori Kimura, MD
- Japan Agency for Medical Research and Development
Investigators
- Principal Investigator: Kiminori Kimura, MD, Tokyo Metropolitan Komagome Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- OP-724-H201