Hepatitis B Virus Infection
Conditions
Brief summary
The primary purpose of this study is to assess the safety and tolerability of single and multiple intravenous (IV) doses of GIGA-2339 in participants with chronic Hepatitis B Virus (HBV) infection.
Interventions
DRUGGIGA-2339
Administered by intravenous infusion
DRUGPlacebo
Administered by intravenous infusion
Sponsors
GigaGen, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Hepatitis B envelope antigen (HBeAg) negative chronic HBV infection for ≥ 6 months, defined as presence of Hepatitis B surface antigen (HBsAg) in serum for ≥ 6 months. * Serum HBsAg concentration between ≥ 100 international units per milliliter (IU/mL) and 2000 IU/mL at screening. * Currently on stable dose of nucleot(s)ide analogues (NAs) (≥ 6 months) and expected to continue while participating in the study, or are not received NAs. * Have serum HBV deoxyribonucleic acid (DNA) concentration ≤ 50 IU/mL at screening (for those who are on NAs); or have serum HBV DNA concentration ≤ 2000 IU/mL at screening (for those who are NOT on NAs). * Male participants must refrain from donating spermatozoa and agree to use highly effective contraception. * Female participants must not be pregnant, or breastfeeding; either should not be a woman of childbearing potential (WOCBP) or if WOCBP should use highly effective contraceptive methods. Key
Exclusion criteria
* Positive for co-infection with hepatitis C virus (HCV), human immunodeficiency virus (HIV), and/or hepatitis D virus (HDV) at screening. * Participants that weigh less than 50 kilograms (kg) and/or have a body mass index (BMI) less than 18.5. * History of documented liver cirrhosis at screening. Patients under liver cirrhosis evaluation at screening will not be eligible until cirrhosis is ruled out. * Liver stiffness \> 8 kilopascal (kPa) at screening. * History of chronic liver disease from another cause, immune complex disease, or autoimmune diseases that in the opinion of the investigator would preclude participation. * Family history of hepatocellular carcinoma (HCC). * Alpha fetoprotein \> 20 nanograms per milliliter (ng/mL). * Presence of a liver imaging reporting and data system (LI-RADS) 4 or 5 liver lesion on imaging 12 months prior to Screening OR, LI-RADS-US findings of US-3 grade on imaging 12 months prior to Screening, OR LIRADS-US grade 3 done prior to the D1 infusion visit, if prior LI-RADS or LI-RADS-US results are not available at Screening. * History of hematopoietic stem cell transplant or solid organ transplant. * Receipt of anti-HBV monoclonal antibody (mAb)/pAb therapy of any kind in the past (including hepatitis B immunoglobulin \[HBIG\]). * History of cardiovascular disease (e.g., coronary artery disease, cardiomyopathy, congestive heart failure, family history of congenital long QT syndrome). Stable hypertension is allowed. * Malignancy diagnosed and/or treated within 5 years prior to Screening, and/or with ongoing treatment for malignancy, with the exception of localized non-metastatic basal cell or squamous cell carcinoma of the skin or in-situ carcinoma of the cervix excised with curative intent. * Participants requiring anti-coagulation therapies (for example warfarin, Factor Xa inhibitors, or anti-platelet agents like clopidogrel). * Male participants with a corrected QT interval using Fridericia's formula (QTcF) \> 450 milliseconds (msec) and female participants with QTcF \> 470 msec on ECG recorded at screening. if the participant has evidence of an intraventricular conduction delay, defined as QRS interval greater than 110 msec, a QTcF is \> 500 msec for both males and females will be excluded. * Known hypersensitivity to any GIGA-2339 excipients or any confirmed significant allergic reactions (urticaria or anaphylaxis) against any drug, or multiple drug allergies (nonactive hay fever is acceptable), or a history of drug or other allergy that, in the opinion of the Investigator, contraindicates participation. * Received or will receive live-attenuated virus vaccinations such as measles, mumps, rubella or varicella within 4 weeks before and up to three months after administration of investigational product (IP).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| SAD and MAD: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAD: Up to Day 105; MAD: Up to Day 245 |
Secondary
| Measure | Time frame |
|---|---|
| SAD and MAD: Maximum Serum Concentration (Cmax) of GIGA-2339 | SAD: Pre-dose and at multiple timepoints post-dose up to Day 105; MAD: Pre-dose and at multiple timepoints post-dose up to Day 245 |
| SAD and MAD: Area Under the Concentration Time Curve (AUC) from 0 to the Last Quantifiable Concentration (AUC0-t) of GIGA-2339 | SAD: Pre-dose and at multiple timepoints post-dose up to Day 105; MAD: Pre-dose and at multiple timepoints post-dose up to Day 245 |
| SAD: AUC From 0 to Infinity (AUC0-∞) of GIGA-2339 | Pre-dose and at multiple timepoints post-dose up to Day 105 |
| SAD: Dose Normalized Maximum Serum Concentration (DN_Cmax). of GIGA-2339 | Pre-dose and at multiple timepoints post-dose up to Day 105 |
| SAD: Dose Normalized AUC From 0 to the Last Quantifiable Concentration (DN_AUC0-t) of GIGA-2339 | Pre-dose and at multiple timepoints post-dose up to Day 105 |
| SAD: Dose Normalized AUC From 0 to Infinity (DN_AUC0-∞) of GIGA-2339 | Pre-dose and at multiple timepoints post-dose up to Day 105 |
| SAD and MAD: Time to Obtain Maximum Concentration (Tmax) of GIGA-2339 | SAD: Pre-dose and at multiple timepoints post-dose up to Day 105; MAD: Pre-dose and at multiple timepoints post-dose up to Day 245 |
| SAD and MAD: Terminal Half-Life (t1/2) of GIGA-2339 | SAD: Pre-dose and at multiple timepoints post-dose up to Day 105; MAD: Pre-dose and at multiple timepoints post-dose up to Day 245 |
| SAD and MAD: Volume of Distribution (Vz) of GIGA-2339 | SAD: Pre-dose and at multiple timepoints post-dose up to Day 105; MAD: Pre-dose and at multiple timepoints post-dose up to Day 245 |
| SAD and MAD: Systemic Clearance (CL) of GIGA-2339 | SAD: Pre-dose and at multiple timepoints post-dose up to Day 105; MAD: Pre-dose and at multiple timepoints post-dose up to Day 245 |
| MAD: Serum Concentration at the End of the Dosing Interval (Ctrough) of GIGA-2339 | Pre-dose and at multiple timepoints post-dose up to Day 245 |
| MAD: AUC Versus Time Curve During the Dosing Interval (AUC0-tau) of GIGA-2339 | Pre-dose and at multiple timepoints post-dose up to Day 245 |
| MAD: Accumulation Ratio Cmax (ARCmax) of GIGA-2339 | Pre-dose and at multiple timepoints post-dose up to Day 245 |
| MAD: Accumulation Ratio AUC (ARAUCs) of GIGA-2339 | Pre-dose and at multiple timepoints post-dose up to Day 245 |
Countries
Australia, Hong Kong, South Korea, Taiwan, United States
Contacts
CONTACTEnrikas Vainorius, MD
Outcome results
None listed