A Study of ARC-521 Injection in Normal Adult Volunteers and Patients With Chronic Hepatitis B (CHB)

• Status: Terminated
• Trial end date: 2016-11-01
• Target enrollment: 0
• Participant gender: All

Summary

Normal healthy volunteer (NHV) participants will enroll sequentially into a total of 6 escalating dose levels (6 subjects per dose level), randomized to receive a single dose of ARC-521 Injection or placebo. The maximum study duration for NHVs is approximately 21 weeks.

Hepatitis B e Antigen (HBeAg)-negative participants with (CHB) will enroll sequentially into 3 dose levels (8 patients per dose level) to receive multiple doses of open label ARC-521 Injection. For each CHB participant the maximum study duration is approximately 37 weeks.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Arrowhead Pharmaceuticals
• Treatments: Acetaminophen; Entecavir; Histamine Antagonists; Histamine H1 Antagonists; Tenofovir

Criteria

Inclusion Criteria:

• Male or female, 18 to 55 years of age inclusive (NHVs) or 18-65 years of age inclusive (CHBs), at the time of informed consent

• Able to provide written informed consent prior to the performance of any study specific procedures

• Body mass index (BMI) between 19.0 and 35.0 kg/m2, inclusive

• A 12-lead ECG at Screening and pre-dose assessment that, in the opinion of the investigator, has no abnormalities that compromise participant's safety in this study

• Must use 2 effective methods of contraception (double barrier contraception or hormonal contraceptive along with a barrier contraceptive (both male and female partners)

• Have suitable venous access for blood sampling

• No abnormal finding of clinical relevance at the Screening evaluation (NHVs only)

• Have a diagnosis of HbeAg-negative chronic HBV infection (CHB patients only)

• Treatment-naive or currently on entecavir/tenofovir for 6 months or longer

Exclusion Criteria:

• Pregnant or lactating

• Acute signs of hepatitis/other infection at Screening or at baseline

• Use within last 14 days or anticipated requirement for anticoagulants, systemic corticosteroids, immunomodulators, or immunosuppressants

• Use of prescription medication within 14 days prior to study treatment that in the opinion of the PI or the Sponsor would interfere with study conduct.

• Known diagnosis of non-alcoholic steatohepatitis [NHVs only] or familial hypercholesterolemia

• Taking interferon alpha (INFalpha) within 6 months of screening [CHBs only]

• History of poorly controlled autoimmune disease or history of autoimmune hepatitis

• Human immunodeficiency virus (HIV) infection

• Seropositive for HBV (NHVs only) or hepatitis C virus (HCV), and/or history of delta virus hepatitis

• Hypertension defined as blood pressure > 170/100 mmHg at screening [NHVs only]

• A history of cardiac rhythm disturbances

• Family history of congenital long QT syndrome, Brugada syndrome or unexplained sudden cardiac death

• Symptomatic heart failure, unstable angina, myocardial infarction, severe cardiovascular disease within 6 months prior to study entry

• History of malignancy within the last 5 years except for adequately treated basal cell carcinoma, squamous cell skin cancer, superficial bladder tumors, or in situ cervical cancer

• History of major surgery within 3 months of Screening

• Regular use of alcohol within one month prior to the Screening visit (more than fourteen units of alcohol per week)

• Evidence of severe systemic acute inflammation, sepsis, or hemolysis [NHVs only]

• Use within 3 months of illicit drugs (cocaine, phencyclidine [PCP], 3,4-methylenedioxymethamphetamine [MDMA], others) or positive test for drugs of abuse at screening.

• History of allergy to bee venom or history of severe hypersensitivity reaction, such as anaphylaxis

• Use of an investigational agent or device within 30 days prior to dosing or current participation in an investigational study

• Clinically significant history of any alcoholic liver disease, cirrhosis, Wilson's disease, hemochromatosis, or alpha-1 antitrypsin deficiency, liver or kidney disease

• Clinically significant history/presence of poorly controlled or decompensated neurological, endocrine, cardiovascular, pulmonary, hematological, immunologic, psychiatric, metabolic, or other uncontrolled systemic disease

• Blood donation (500 mL) within 7 days prior to study treatment administration [NHVs only]

• History of fever (>38.0ºC/100.4ºF) within 2 weeks of Screening [NHVs only]

• Any concomitant medical or psychiatric condition or social situation that impacts compliance or involves additional safety risk

• History of coagulopathy (including deep vein thrombosis and pulmonary embolism) or stroke within 6 months of baseline, and/or concurrent anticoagulant medication(s)

• Presence of cholangitis, cholecystitis, cholestasis, or duct obstruction