A Study to Assess the Safety, Tolerability, and Pharmacokinetics of GIGA-2339 in Participants With Chronic Hepatitis B Virus Infection

Official title

A Randomized, Double-Blind, Placebo-Controlled, Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of GIGA-2339 Administered as a Single Ascending Dose and Multiple Ascending Doses in Participants With Chronic Hepatitis B Virus Infection

Overview

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

• Drug GIGA-2339
  Administered by intravenous infusion
• Drug Placebo
  Administered by intravenous infusion

Primary outcome measures

• SAD and MAD: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [Time frame: SAD: Up to Day 105; MAD: Up to Day 245]

Secondary outcome measures (12)

• SAD and MAD: Maximum Serum Concentration (Cmax) of GIGA-2339 [Time frame: 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 [Time frame: 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 [Time frame: Pre-dose and at multiple timepoints post-dose up to Day 105]
• SAD: Dose Normalized Maximum Serum Concentration (DN_Cmax). of GIGA-2339 [Time frame: 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 [Time frame: 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 [Time frame: Pre-dose and at multiple timepoints post-dose up to Day 105]
• SAD and MAD: Time to Obtain Maximum Concentration (Tmax) of GIGA-2339 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: Pre-dose and at multiple timepoints post-dose up to Day 245]

Eligibility criteria

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.

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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Sequential

Masking

Double blind

Primary purpose

Treatment

Study locations

United States · 12 centers

• Grifols Investigative site — Chandler
• Grifols Investigative site — Huntington Beach
• Grifols Investigative site — Lake Forest
• Grifols Investigative site — Long Beach
• Grifols Investigative site — Oakland
• Grifols Investigative Site — Peachtree Corners
• Grifols Investigative Site — Iowa City
• Grifols Investigative Site — Lenexa
• … and 4 more centers

Australia · 2 centers

• Grifols Investigate Site — Concord
• Grifols Investigative site — Fortitude Valley

Hong Kong · 2 centers

• Grifols Investigative site — Hong Kong
• Grifols Investigative site — Shatin

South Korea · 2 centers

• Grifols Investigative site — Seogu
• Grifols Investigative site — Songpa-dong

Taiwan · 1 center

• Grifols Investigative site — Sanmin

Identifiers

NCT: NCT07024641 · GC2301

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗