A study to evaluate the safety and tolerability of multiple doses of ND-L02-s0201 in subjects with moderate to extensive hepatic fibrosis
- Conditions
- Moderate to extensive progressive hepatic fibrosis (METAVIR F3-4)MedDRA version: 18.0Level: PTClassification code 10019668Term: Hepatic fibrosisSystem Organ Class: 10019805 - Hepatobiliary disordersTherapeutic area: Diseases [C] - Digestive System Diseases [C06]
- Registration Number
- EUCTR2014-004882-26-BG
- Lead Sponsor
- itto Denko Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 24
1. The subject is a male or female between 18 and 75 years of age.
2. The subject has a diagnosis of METAVIR F3-4 hepatic fibrosis as determined by liver biopsy done within 12 months before screening (Cohort 1) or at the pre-dose biopsy within 6 weeks before treatment (Cohorts 2 and 3). METAVIR (Bedossa & Poynard, 1996) scores are defined as follows:
F0 = No fibrosis
F1 = Portal fibrosis without septa
F2 = Portal fibrosis with rare septa
F3 = Numerous septa without cirrhosis
F4 = Cirrhosis
3. The subject has adequate and stable synthetic hepatic function (albumin = 3 g/dL, international normalized ratio [INR] = 1.4 x upper limit of normal [ULN] and stable by prior medical history).
4. The subject has adequate and stable hepatic function as measured by alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST), gamma glutamate transferase (GGTP), and total bilirubin (ALT/AST = 5 x ULN, ALP = 4 x ULN, GGTP = 4 x ULN, bilirubin = 2x ULN and stable by prior medical history).
5. The subject has platelet count = 75,000/mm3, hemoglobin = 10 g/dL, and white blood cell count (WBC) > 3000/µL.
6. The subject has no signs of decompensated liver disease (ascites, hepatic encephalopathy, or variceal bleeding).
7. The subject has no clinically significant abnormalities on 12-lead electrocardiogram (ECG).
8. The subject has no other intercurrent medical conditions or infections considered clinically significant by the Investigator.
9. The subject’s clinical laboratory assessments are within the laboratory limits of normal values or not considered clinically significant by the Investigator.
10. The subject’s vitamin A levels at screening must be less than or equal to the upper limit of normal (ULN 95 µg/dL or 3.32 µmol/L).
11. Any male subject, if sexually active, agrees to use barrier contraceptive techniques as defined in the protocol. If female, the subject must be of non-childbearing potential as defined in the protocol.
12. Subjects who are active substances abusers may be enrolled at the discretion of the Principal Investigator.
13. The subject is willing and able to provide written informed consent and comply with the study procedures and visit schedule, including follow-up visits.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 18
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 6
1. The subject has any disease or condition which, in the opinion of the Investigator, might compromise the hematologic, cardiovascular, pulmonary, renal, gastrointestinal, hepatic, skeletal, or central nervous system; or other conditions that may interfere with the absorption, distribution, metabolism, or excretion of ND-L02-s0201, or would place the subject at increased risk.
2. The subject is on ongoing therapy for HCV/HBV, or received therapy for HCV/HBV within 12 weeks prior to administration of study drug.
3. The subject is on interferon therapy for any disease, or received interferon therapy for any disease within 12 weeks prior to administration of study drug.
4. The subject has a history of bone disease, including osteoporosis and osteomalacia, Paget’s disease of bone, or a history of unexplained fractures or fractures after minimal trauma.
5. The subject has alpha-fetoprotein (AFP) = 50 ng/mL or signs of abnormality or hepatocellular carcinoma on ultrasound survey of the liver.
6. The subject’s laboratory test results include abnormal values considered to be clinically significant by the Investigator.
7. The subject participated in a concurrent interventional study with the last intervention occurring within 12 weeks prior to administration of study drug.
8. The subject took vitamin A or vitamin D supplements or multi-vitamins that contain vitamin A or vitamin D between the screening visit and administration of study drug.
9. The subject has a history, within the last 2 years, of alcohol abuse, significant mental illness, or physical dependence on any opioid.
10. The subject has, in the opinion of study staff, veins unsuitable for repeated venipuncture or IV infusion (eg, veins that are difficult to locate, access or puncture; veins with a tendency to rupture during or after puncture).
11. The subject has received recent treatment with alternative therapies, which, in the opinion of the Investigator, could potentially confound clinical or laboratory assessments.
12. The subject lost more than 500 mL of blood within 56 days prior to administration of study drug.
13. The subject has a body mass index (BMI) > 38 kg/m2.
14. The subject has a history of human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome-related illness (AIDS).
15. The subject has a history of malignancy within the last 5 years, with the exception of basal cell carcinoma.
16. The subject is a woman of childbearing potential.
17. The subject has a history of hypersensitivity to H2-receptor antagonists.
18. There is any other reason that, in the opinion of the Investigator or the QDS Medical Monitor, makes the subject unsuitable for enrollment.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method