Study Evaluating ABI-H2158-Containing Regimens in Chronic Hepatitis B Infectio
- Conditions
- Chronic Hepatitis B InfectionMedDRA version: 20.1Level: LLTClassification code 10047450Term: Viral hepatitis BSystem Organ Class: 100000004862Therapeutic area: Diseases [C] - Virus Diseases [C02]
- Registration Number
- EUCTR2019-004902-85-GB
- Lead Sponsor
- Assembly Biosciences
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 80
1. Willing and able to provide informed consent
2. Male or female between the ages 18 and 65 years (inclusive)
3. Female subjects must be non-pregnant and have a negative serum pregnancy test at Screening and a negative urine pregnancy test predose on Day 1.
4. Chronic hepatitis B infection, defined as HBV infection for =6 months documented, for example, by at least two measurements of HBsAg positivity and/or detectable HBV DNA =6 months apart (inclusive of Screening). For subjects without clear documentation of CHB, serum immunoglobulin M (IgM) antibody to the HBV core-related antigen (HBcrAb) must be negative at Screening to exclude acute HBV infection.
5. Body mass index (BMI) 18 to 36 kg/m2 and a minimum body weight of 45 kg (inclusive)
6. HBV DNA =2 × 105 IU/mL
7. HBeAg =500 IU/mL at Screening
8. HBsAg >1000 IU/mL at Screening
9. Lack of cirrhosis or advanced liver disease as documented by the following:
o Liver biopsy results of METAVIR F0-F2 (absence of bridging fibrosis or cirrhosis) within 1 year of Screening
OR
o Fasting FibroScan =8 kPa within 3 months of Screening (including Screening visit) or other Sponsor approved hepatic imaging study (hepatic magnetic resonance imaging [MRI], or hepatic ultrasound by a ultrasonographer with expertise in evaluation of liver fibrosis) within 6 months of Screening indicating lack of cirrhosis or advanced liver disease (F0-F2 or equivalent).
10. Agreement to comply with protocol-specified contraceptive requirements.
11. Agreement to abstain from alcohol abuse [defined as alcohol consumption exceeding 2 standard drinks per day on average (1 standard drink = 10 grams of alcohol)] and the use of illicit substances from screening until end of the study
12. In good general health, except for CHB
13. Have the ability to take oral medication and, in the opinion of the Investigator, be willing to adhere to study treatment
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 72
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 8
1. Prior treatment for CHB; specifically
a. lamivudine, telbivudine or adefovir (any duration)
b. NrtI treatment for > 4 weeks
c. HBV core inhibitors (any duration)
d. Previous treatment with an investigational agent for HBV infection
2. Co-infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis E virus (HEV), or hepatitis D virus (HDV)
3. Females who are lactating, or wish to become pregnant during the course of the study
4. History or evidence of advanced liver disease or hepatic decompensation (including jaundice, ascites, portal hypertension, gastrointestinal bleeding esophageal varices, hepatic encephalopathy,) at any time prior to, or at the time of Screening.
5. History of persistent alcohol abuse (alcohol consumption exceeding 2 standard drinks per day on average [1 standard drink = 10 grams of alcohol]) or illicit drug abuse within 3 years before Screening
6. Clinically significant cardiac or pulmonary disease, chronic or recurrent renal or urinary tract disease, liver disease other than CHB, endocrine disorder, autoimmune disorder, diabetes mellitus requiring treatment with insulin or hypoglycemic agents, neuromuscular, musculoskeletal, or mucocutaneous conditions requiring frequent treatment, seizure disorders requiring treatment, ongoing infection or other medical conditions requiring frequent medical management or pharmacologic or surgical treatment that in the opinion of the Investigator or the Sponsor makes the subject unsuitable for study participation.
7. History of hepatocellular carcinoma (HCC)
8. A history of malignancy other than HCC unless the subject’s malignancy has been in complete remission off chemotherapy and without additional medical or surgical interventions during the 3 years before Screening
9. Poorly controlled or unstable hypertension; or sustained systolic blood pressure (BP) = 160 mmHg or <90 mmHg, or diastolic BP >95 mmHg or <50 mmHg at Screening
10. History or presence of electrocardiogram (ECG) abnormalities deemed clinically significant as described in the protocol.
11. History of hypersensitivity or idiosyncratic reaction to any components or excipients of the investigational drug or PBO formulation
12. History of any significant food or drug-related allergic reactions such as, anaphylaxis, Stevens-Johnson syndrome, or urticaria
13. The following exclusionary laboratory results at Screening and Baseline visit:
a. Platelet count <100,000/mm3
b. Albumin < lower limit of normal (LLN)
c. Total bilirubin >1.2 × upper limit of normal (ULN) unless known Gilbert’s syndrome; subjects with Gilbert’s syndrome are eligible for study participation if the direct bilirubin is within the normal range
d. Direct bilirubin >1.2 × ULN
e. ALT >5 × ULN
f. Serum alpha fetoprotein (AFP) =100 ng/mL. If AFP at Screening is > ULN but <100 ng/mL, the subject is eligible if a hepatic imaging study prior to initiation of study drug reveals no lesions indicative of possible HCC.
g. International Normalized Ratio (INR) >1.5 × ULN
h. Glomerular filtration rate (GFR) <60 mL/min/1.73 m2 by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation [Levey 2009]
i. Serum hemoglobin A1c (HbA1c) >6.5%
j. Any other laboratory abnormality deemed clinically significant by the Sponsor or the Investigator
14. Subjects receiving prohibited concomitant medications, grapefruit juice, herbal or over-the counter medications (Section 6.4.1) within 7 days or 5 half-lives (if known), whichever is longer, p
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