Study of GS-4321 for Healthy People and Patients With Chronic Hepatitis Delta Virus Infection

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What is this study about?

This study is looking at Chronic Hepatitis Delta, which is a liver infection caused by the hepatitis delta virus. The study will test a treatment called GS-4321, which is a type of monoclonal antibody, meaning it is a laboratory-made protein designed to target specific parts of the virus. Some participants will receive GS-4321 while others will receive placebo. The purpose of the study is to see how safe the treatment is, how well it is tolerated by the body, how the body processes the medication, and whether it can reduce the amount of virus in the blood.

The study has two parts. In Part A, healthy volunteers will receive a single dose of GS-4321 given either as an injection under the skin or into a vein. This part will help researchers understand how the medication moves through the body and whether it causes any unwanted effects. In Part B, people who have chronic hepatitis delta infection will receive multiple doses of GS-4321 over time. These participants must already be taking certain medications for hepatitis B, such as entecavir, tenofovir alafenamide, or tenofovir disoproxil fumarate. Researchers will check the virus levels in the blood and monitor liver function through blood tests and measurements of liver stiffness using a special imaging method called elastography.

Throughout the study, participants will have regular visits where blood samples will be taken to measure virus levels, check how the liver is working, and look for any side effects. The study will also check whether participants develop immune responses to the medication by looking for antidrug antibodies in the blood. For those in Part B, the treatment period will last up to 96 weeks, with regular monitoring to see how well the medication works in reducing virus levels and improving liver health markers such as alanine aminotransferase, which is a substance in the blood that can indicate liver inflammation.

1 Initial screening and preparation

Your eligibility for the study will be confirmed. You must be between 18 and 70 years of age.

If you are participating in Part A, you will be confirmed as healthy based on medical history, physical examination, vital signs, and laboratory tests. Your body mass index (a measure of body fat based on height and weight) must be 30.0 or less.

If you are participating in Part B, you must have chronic hepatitis delta for at least 6 months. You must already be taking one of the following medications: entecavir, tenofovir alafenamide, or tenofovir disoproxil fumarate.

For Part B, your liver condition will be assessed. You must have either non-cirrhotic liver disease (liver stiffness less than 12.5 measured by a scan) or compensated cirrhotic liver disease (liver stiffness 12.5 or higher but with stable liver function).

For Part B, your hepatitis delta virus levels must be greater than 500 international units per milliliter, and your alanine aminotransferase (a liver enzyme) levels must meet specific criteria.

If you are of childbearing potential and engage in heterosexual intercourse, you must agree to use specific contraception methods during the study.

2 Treatment administration in Part A

If you are in Part A (healthy participants), you will receive a single dose of GS-4321 or placebo.

The medication will be administered either as an injection under the skin (subcutaneous) or directly into a vein (intravenous).

The dose will vary as part of the study design to evaluate increasing dose levels.

3 Treatment administration in Part B

If you are in Part B (participants with chronic hepatitis delta), you will receive multiple doses of GS-4321 or placebo.

The medication will be given as an injection.

The dose will vary as part of the study design to evaluate increasing dose levels.

You will continue receiving doses over a period of 24 weeks.

4 Monitoring during treatment in Part A

If you are in Part A, blood samples will be collected at specific times to measure how the medication moves through your body.

You will be monitored for any side effects or adverse events.

Laboratory tests will be performed to check for any abnormalities.

Your body will be checked for the development of antidrug antibodies (proteins your immune system might produce in response to the medication).

5 Monitoring during treatment in Part B

If you are in Part B, you will have regular visits at Weeks 4, 8, 12, 16, 20, and 24 during the treatment period.

Blood samples will be collected to measure hepatitis delta virus levels in your blood.

Your alanine aminotransferase levels (liver enzyme) will be checked regularly.

Blood samples will be collected to measure how the medication moves through your body.

You will be monitored for any side effects or adverse events.

Laboratory tests will be performed to check for any abnormalities.

Your body will be checked for the development of antidrug antibodies.

Tests will be performed to check if the virus develops any changes that might affect how well the medication works.

6 Follow-up period for Part B

If you are in Part B, after completing the 24-week treatment period, you will continue to be monitored during a follow-up period.

Follow-up visits will occur at Weeks 36, 48, 60, 72, 84, and 96.

During these visits, your hepatitis delta virus levels and liver enzyme levels will continue to be measured.

Your liver stiffness will be measured at Weeks 24, 48, and 96 using a scan to assess any changes in your liver condition.

You will continue to be monitored for any side effects or adverse events.

The total duration of your participation, including treatment and follow-up, will be 96 weeks (approximately 2 years).

7 Study completion

After completing all scheduled visits and assessments, your participation in the study will be complete.

All collected data will be used to evaluate the safety, tolerability, and effectiveness of GS-4321.

Who Can Join the Study?

Part A Requirements:

You must be between 18 and 69 years old
You must be able to understand and sign a consent form agreeing to participate in the study
You must be willing to follow the treatment plan and attend all follow-up visits
If you are able to become pregnant or father a child and are sexually active with partners of the opposite sex, you must agree to use specific birth control methods as required by the study
You must be healthy enough to participate in the study, as determined by your medical history, physical examination, vital signs (measurements like blood pressure, heart rate, and temperature), and laboratory test results from screening
Your body mass index or BMI (a measure of body fat based on your height and weight) must be 30.0 or less at the time of screening and when you are admitted to the study

Part B Requirements:

You must be between 18 and 69 years old
You must be able to understand and sign a consent form agreeing to participate in the study
You must be willing to follow the treatment plan and attend all follow-up visits
If you are able to become pregnant or father a child and are sexually active with partners of the opposite sex, you must agree to use specific birth control methods as required by the study
You must have had chronic hepatitis delta (a long-term liver infection caused by the hepatitis delta virus) for at least 6 months before screening, confirmed by your previous medical records
You must be taking one of the following medications: entecavir, tenofovir alafenamide, or tenofovir disoproxil fumarate (medicines used to treat hepatitis B virus infection) at or before joining the study; these medications can be part of a combination pill used to treat HIV
Your liver must be either without cirrhosis (scarring of the liver) or have compensated cirrhosis, which means: For no cirrhosis, your liver stiffness (measured by a special test called elastography) must be less than 12.5 within 6 months before or at screening; For compensated cirrhosis, your liver stiffness must be 12.5 or higher within 6 months before or at screening, and your Child-Turcotte-Pugh score (a scoring system that measures how well your liver is functioning) must be less than 7 at screening
Your HDV RNA (the amount of hepatitis delta virus genetic material in your blood) must be greater than 500 units per milliliter at screening
Your ALT level (a liver enzyme that shows liver health) must be greater than the upper limit of normal or ULN (the highest normal value) but less than 10 times the upper limit of normal at screening for some groups, or less than 10 times the upper limit of normal for another group

Who Cannot Join the Study?

The study does not list specific reasons that would prevent you from participating. Your doctor will review your individual health situation to determine if this study is right for you.
General factors that typically affect study participation include other medical conditions you may have, medications you are currently taking, and results from your laboratory tests.
Women who are pregnant or breastfeeding (feeding a baby with breast milk) may not be able to participate.
If you have severe liver damage or other serious health problems, you may not be eligible.
Certain infections or diseases affecting your immune system (the body’s defense against illness) may prevent participation.
If you are taking medications that could interfere with the study drug, you may not be able to join.
People with known allergies to similar medications may be excluded.
Your doctor will discuss with you whether you meet all the requirements to participate safely in this study.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country	Status
Medizinische Hochschule Hannover	Hanover	Germany

Other Sites

Site Name	City	Country
University Multiprofile Hospital For Active Treatment Sofiamed OOD	Sofia	Bulgaria
MBAL Sveta Marina EAD	Varna	Bulgaria
Gastromedica S.R.L.	Iasi	Romania
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico	Milan	Italy
Institutul National De Boli Infectioase Prof.Dr.Matei Bals	Bucharest	Romania
Fhtmqcww Ded Vuoqxy Bmeav	Bucharest	Romania

Trial status

Country	Status	Recruitment Start
Bulgaria	Recruiting	05.02.2026
Germany	Not yet recruiting	05.02.2026
Italy	Recruiting	05.02.2026
Romania	Recruiting	05.02.2026

Trial locations

Investigated drugs:

GS-4321

GS-4321 is an investigational medication being studied for the treatment of chronic hepatitis delta, which is a liver infection. This medication is being tested to see if it can help fight the virus that causes this infection. In this study, the medication will be given in two different ways: as an injection under the skin or directly into a vein. Researchers want to learn how safe the medication is, how well the body processes it, and whether it can effectively reduce the virus in people with chronic hepatitis delta.

Investigated diseases:

Hepatitis D

Chronic Hepatitis Delta – Chronic Hepatitis Delta is a liver infection caused by the hepatitis delta virus, which can only occur in people who are already infected with hepatitis B virus. The virus attacks liver cells and causes inflammation that persists over time. This ongoing inflammation can lead to progressive damage to the liver tissue. Over months and years, the continued liver damage may result in scarring of the liver. As the disease advances, the liver’s ability to function properly becomes increasingly impaired. The condition represents one of the more serious forms of viral hepatitis affecting the liver.

Trial ID:

2025-522729-36-00

Protocol code:

GS-US-567-6968

NCT ID:

NCT07096193

Trial Phase:

Phase I and Phase II (Integrated) – First administration to humans

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Study of GS-4321 for Healthy People and Patients With Chronic Hepatitis Delta Virus Infection

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?