Trial to Evaluate the Efficacy, Safety and Pharmacokinetics of RBD1016 in Participants With Chronic Hepatitis D

A Phase 2a, Multicentre Trial to Evaluate the Efficacy, Safety and Pharmacokinetics of RBD1016 in Participants With Chronic Hepatitis D Virus Infection, Including a Randomised, Single Blinded, Placebo-controlled Exploratory Part

The goal of this clinical trial is to learn if drug RBD1016 works to treat chronic hepatitis D virus infection in adults. It will also learn about the safety of drug RBD1016. The main questions it aims to answer are:

Does drug RBD106 reduce the HDV RNA levels? What medical problems may participants experience when taking drug RBD1016? Researchers will compare drug RBD1016 to a placebo to see if drug RBD1016 works to treat chronic hepatitis D.

Participants will:

Receive drug RBD1016 or a placebo several times throughout the trial. Visit the clinic once every 4-6 weeks for checkups and tests.

This is a multicentre, randomised, partly blinded, placebo-controlled clinical trial to evaluate the efficacy, safety and pharmacokinetics (PK) of RBD1016 subcutaneous injections in participants with chronic HDV infection.

First part of the trial: There will be 2 treatment groups - an active group (n=10) and a deferred active group (n=5), with participants allocated randomly. In the active group, participants will receive RBD1016. In the deferred active group, participants will receive 4 doses of placebo followed by deferred treatment with doses of RBD1016.

Both groups will be on a stable nucleoside analogue (NA) treatment course during the trial . All participants will be blinded to the trial treatment for the 16 weeks after the first dose. Then, investigators and other clinic staff will be unblinded, i.e., they will know which treatment the participants receive at all times.

Open-label extension part (site 01 only): continued IMP-treatment with additionally 3 doses of IMP administered 12 weeks apart. This part of the trial is conducted to collect long-term safety data and further exploratory efficacy measures. Only participants who may benefit from continued treatment in the ,trial, according to the judgement of the investigator, will be eligible for the open-label extension part of the trial.

Inclusion Criteria:

1. Willing and able to give written informed consent for participation in the trial.
2. Male or female participant aged 18 to 65 years, inclusive.
3. Body mass index (BMI) ≥ 18 and ≤ 35 kg/m2 at the time of the screening visit.
4. Documented evidence of HDV infection in medical history, i.e., HDV antibodies (HDVAb) and/or HDV RNA positive test results within at least 6 months prior to screening.
5. Documented evidence of HBV infection in medical history, i.e., HBsAg and/or HBV DNA positive test results within at least 6 months prior to screening.
6. Documented absence of liver cirrhosis, defined as an LSM ≥ 10 kPa measured on FibroScan® elastography at screening.

Exclusion Criteria:

1. Laboratory results at screening as follows, or any clinically significant laboratory parameter outliers that may interfere with the evaluation of efficacy and/or safety in the trial, at the discretion of the Investigator:

   • α-fetoprotein (AFP) > 50 µg/L.
   • Albumin concentration < 3.0 g/dL.
   • International normalized ratio (INR) > 1.5.
   • Platelet count < 90 × 109/L.
   • Direct bilirubin > 2 × ULN, Gilbert syndrome excluded.
   • Creatinine concentration > 1.5 × ULN.
   • Creatinine clearance < 60 mL/min, according to the Cockcroft-Gault equation.

2. Positive result at screening for hepatitis C virus (HCV) and/or human immunodeficiency virus (HIV) and/or prior diagnosis of syphilis, acute hepatitis A and/or acute hepatitis E.

3. Prior diagnosis of other liver diseases of non-HBV or non-HDV aetiology, including autoimmune liver disease (e.g., autoimmune hepatitis, primary biliary cholangitis or primary sclerosing cholangitis), inherited metabolic liver disease (e.g., haemochromatosis, Wilson's disease, familial intrahepatic cholestasis), drug-induced liver disease and/or non alcoholic steatohepatitis (NASH) assessed as moderate or above, at the discretion of the Investigator.

4. Prior or current diagnosis of liver cirrhosis.

5. History of or active hepatic decompensation, e.g., ascites, variceal bleeding or hepatic encephalopathy, at the discretion of the Investigator.

6. History of organ transplantation, previous or concurrent HCC or imaging finding suggesting malignant liver lesions, at the discretion of the Investigator.

7. Signs of liver malignancy in abdominal ultrasound at screening.