Study to Evaluate Switching to Brelovitug for the Treatment of CHD in Participants Receiving Bulevirtide

Official title

A Phase 2b/3, Open-Label, Multicenter Trial Evaluating the Efficacy and Safety of Switching to Brelovitug for the Treatment of Chronic Hepatitis Delta Infection in Participants Receiving Bulevirtide (AZURE-3)

Overview

This is a Phase 2b/3, randomized, open-label, multicenter trial evaluating the efficacy and safety of switching from bulevirtide to brelovitug for the treatment of chronic hepatitis Delta infection (CHD).

Detailed description

This is a Phase 2b/3, open-label, multicenter study evaluating the efficacy and safety of switching participants on bulevirtide to brelovitug for the treatment of chronic hepatitis delta (CHD).

Interventions

• Drug Brelovitug (BJT-778)
  Brelovitug (BJT-778), 300 mg administered subcutaneously once weekly for 96 weeks.
• Drug Bulevirtide
  Bulevirtide - once daily. Brelovitug (BJT-778) - 300 mg once weekly for 72 weeks following bulevirtide.

Primary outcome measures

• Proportion of participants with undetectable HDV RNA (<LLOQ Target not detected [TND]) [Time frame: Week 24]

Secondary outcome measures (12)

• Incidence and severity of treatment-emergent adverse events (TEAEs) [Time frame: Up to Week 96]
• Proportion of participants who permanently discontinue treatment due to an adverse event [Time frame: Up to Week 96]
• Change from baseline in serum total bile salts [Time frame: Up to Week 96]
• Proportion of participants achieving virologic response (HDV RNA ≥2 log10 IU/mL decline from baseline or HDV RNA <LLOQ, TND) [Time frame: Up to Week 96]
• Proportion of participants achieving HDV RNA < LLOQ at Weeks 24, 48, 72 and 96. [Time frame: Up to Week 96]
• Proportion of participants achieving undetectable HDV RNA (HDV RNA < LLOQ, TND) at Weeks 48, 72, and 96. [Time frame: Up to Week 96]
• Proportion of participants achieving normal ALT at Weeks 24, 48, 72 and 96. [Time frame: Up to Week 96]
• Proportion of participants achieving normal ALT with virologic response (HDV RNA ≥2 log10 IU/mL decline from baseline or HDV RNA <LLOQ, TND) [Time frame: Up to Week 96]
• Proportion of participants achieving normal ALT with HDV RDA < LLOQ at Weeks 24, 48, 72 and 96. [Time frame: Up to Week 96]
• 11. Proportion of participants achieving normal ALT with undetectable HDV RNA (HDV RNA < LLOQ, TND) at Weeks 24, 48, 72 and 96 [Time frame: Up to Week 96]
• Change from baseline in HDV RNA [Time frame: Up to Week 96]
• Change from baseline in ALT levels [Time frame: Up to Week 96]

Eligibility criteria

Inclusion criteria

• Willing and able to provide written informed consent.
• Male or female, ≥18 years of age at Screening.
• Taking or willing to take TDF, TAF, or ETV at baseline, and willing to remain on stable treatment for the duration of the study.
• Currently taking bulevirtide treatment for CHD for ≥6 months at the time of Screening.
• HDV RNA ≥100 IU/mL at Screening.

Exclusion criteria

• Evidence of decompensated liver disease (e.g., CTP Class B or C, history of hepatic encephalopathy, clinically significant ascites, or variceal bleeding).
• Known history of immune-complex disease.
• Active or clinically significant co-infection with hepatitis C virus (HCV) or human immunodeficiency virus (HIV).
• Evidence of other significant liver diseases (e.g., autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis).
• History of hepatocellular carcinoma (HCC) or evidence of HCC on screening imaging.

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

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

France · 10 centers

• CHU de Bordeaux — Bordeaux
• Clermont-Ferrand University Hospital — Clermont-Ferrand
• Hospital Beaujon — Clichy
• Henri Mondor University Hospital (APHP) — Créteil
• CHU Grenoble Alpes Hopital Nord Michallon — Grenoble
• CHU Limoges — Limoges
• Hospital De La Croix Rousse — Lyon
• Hopital Saint-Eloi — Montpellier
• … and 2 more centers

Romania · 6 centers

• Centrul Medical Unirea S.R.L — Iași
• National Institute Of Infectious Diseases Prof. Dr. Matei Bals — Bucharest
• Fundeni Clinical Institute — Bucharest
• Clinical Hospital for Infectious and Tropical Diseases Dr. Victor Babes — Bucharest
• National Institute Of Infectious Diseases Prof. Dr. Matei Bals — Bucharest
• Spitalul Clinic de Boli Infectioase Constanta — Constanța

United Kingdom · 6 centers

• Castle Hill Hospital — Cottingham
• Cardiff and Vale University Health Board — Cardiff
• Barts Health NHS Trust — London
• King's College Hospital NHS Foundation Trust — London
• Chelsea and Westminster Hospital — London
• Manchester University Nhs Foundation Trust — Manchester

Germany · 4 centers

• University Hospital of Dusseldorf — Düsseldorf
• Goethe University Frankfurt — Frankfurt
• Medizinische Hochschule Hannover — Hanover
• Universitatsmedizin Rostock — Rostock

Czechia · 3 centers

• Fakultni Nemocnice Brno (University Hospital Brno) — Brno
• Klin Med Ltd. (KLIN MED s.r.o.) — Prague
• Institut klinicke a experimentalni mediciny- IKEM (Institute for Clinical and Experimental — Prague

Spain · 3 centers

• Vall d'Hebron Hospital — Barcelona
• Hospital Clinic I Provincial De Barcelona — Barcelona
• Hospital Universitario Ramon y Cajal — Madrid

Austria · 2 centers

• Medical University of Graz — Graz
• Medizinische Universitat Innsbruck — Innsbruck

Italy · 1 center

• Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico — Milan

Identifiers

NCT: NCT07454837 · BJT-778-303

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗