A Global, Randomized, Open-label, Multicenter Phase 3 Trial Evaluating BJT-778 vs Bulevirtide for the Treatment of Chronic Hepatitis Delta Infection (AZURE-2)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Bluejay Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

28 Aug 2025 → ongoing

Decision date (initial)

2025-07-21

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Bluejay Therapeutics, Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Others

To evaluate the efficacy of brelovitug compared with bulevirtide treatment of CHD at Week 48

Secondary objectives 7

1. To evaluate the safety and tolerability of brelovitug and in comparison, to bulevirtide treatment
2. To characterize the efficacy of brelovitug and in comparison, to bulevirtide on HDV
3. To characterize the effect of brelovitug and in comparison, to bulevirtide on HDV disease progression, including assessment of HDV-related liver disease progression
4. To evaluate the efficacy of switching from bulevirtide to brelovitug (Arm 2)
5. To evaluate the safety and tolerability of switching from bulevirtide to brelovitug (Arm 2)
6. To assess and compare to bulevirtide the effect of brelovitug on Health-Related Quality of Life (HRQoL)
7. To evaluate the rate of undetectable HDV RNA after 96 weeks of treatment in participants who do not rollover to the extended treatment protocol

Conditions and MedDRA coding

Chronic Hepatitis D Infection

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Willing and able to provide written informed consent
2. Male or female, ≥18 years of age at Screening
3. Confirmation of chronic HDV infection, defined as a positive for anti-HDV antibody test or HDV RNA at least 6 months prior to Day 1. If prior documentation is not available, then HDV RNA positivity along with evidence of fibrosis (liver stiffness of ≥7 kPa) is acceptable.
4. HDV RNA >500 IU/mL at Screening
5. ALT >ULN at Screening
6. Taking or willing to take tenofovir disoproxil fumarate (TDF), tenofovir alafenamide fumarate (TAF), or entecavir (ETV) at baseline, and willing to remain on stable treatment for the duration of the study.

Exclusion criteria 16

1. Pregnant or nursing females
2. Male or female participants of childbearing potential unwilling to comply with contraception requirements during the study
3. Current, prior history, or is under evaluation for any of the following: a) Difficulty with blood collection and/or poor venous access for the purposes of phlebotomy b) Clinical hepatic decompensation (i.e., ascites, encephalopathy variceal hemorrhage). Incidental small ascites on imaging without other clinical symptoms/signs would not exclude the participants. c) Hepatocellular carcinoma; suspected HCC on ultrasound at Screening d) Vasculitis e) Extrahepatic disorders possibly related to HBV immune complexes (e.g., glomerulonephritis, polyarteritis nodosa) f) Solid organ or bone marrow transplantation g) Significant pulmonary disease (e.g., O2-dependent or FEV1 ≤50% predicted value) h) Significant cardiac disease (e.g., history of myocardial infarctions within 6 months, any history of ventricular tachycardia, congestive heart failure, dilated cardiomyopathy with left ventricular ejection fraction <40%) i) Malignancy diagnosed or treated within 5 years (recent localized treatment of squamous or non-invasive basal cell skin cancers is permitted; cervical carcinoma in situ is allowed if appropriately treated prior to Screening).
4. CTP >6 (Class B or C) (see Section 6.7.7.2)
5. Presence of other liver disease(s) (non-HBV/HDV), such as nonalcoholic steatohepatitis (NASH), alcohol associated hepatitis, cholestatic liver disease, other viral (e.g., HCV or hepatitis A virus) or non-viral hepatitis that has the potential to impact interpretation of data. Exceptions to this criterion include fatty liver without any signs of steatohepatitis or past HCV infection that has resolved or been successfully treated (HCV RNA negative ≥6 months) prior to Screening.
6. Uncontrolled HIV infection defined as having quantifiable HIV RNA levels in the blood at Screening
7. History of hypersensitivity to any of the components in the brelovitug or bulevirtide formulation
8. Screening laboratory results as follows, or any other clinically significant abnormalities in Screening laboratory values that would render a participant unsuitable for inclusion: a) Platelet count <50,000/mm3 b) Hemoglobin <10.0 g/dL c) Creatinine clearance by Cockcroft-Gault (CLCr) <50 mL/min d) Alpha fetoprotein >100 ng/mL
9. Treatment with an investigational drug, a biological agent, or device within 4 weeks of baseline or 5 half-lives, whichever is longer
10. Received bulevirtide at any time prior to Screening, or unwilling or unable to receive bulevirtide treatment.
11. Unwilling or unable to self-inject study medication, including daily injection with bulevirtide
12. Use of any prohibited concomitant medications, including any interferon within 12 weeks prior to Screening, as described in Section 7.8, or described in the Hepcludex SmPC/Product Information
13. Regular alcohol misuse, defined as weekly intake of ≥14 drinks per week (average of ≥2 drinks per day) within 12 months of Screening
14. Clinically relevant drug abuse (excluding cannabis) within 12 months of Screening
15. Unwillingness to comply with study procedures as specified by this protocol, or unwillingness to cooperate fully with the Investigator
16. Have any other conditions (medical, social, psychiatric, or other), which in the opinion of the Investigator would make the participant unsuitable for inclusion, or could interfere with the participant participating in or completing the study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The proportion of participants who achieve a composite endpoint defined as undetectable HDV RNA and ALT normalization. • Undetectable HDV RNA is defined as HDV RNA < the lower limit of quantification [LLOQ], target not detected (TND) • ALT normalization is defined as a decrease in ALT from baseline to ≤ULN

Secondary endpoints 9

1. 1. Safety endpoint will evaluate: • Incidence and severity of treatment-emergent adverse events (TEAE) • Proportion of participants who permanently discontinue treatment due to an adverse event Comparison with bulevirtide will include data through 48 weeks
2. 2. The proportion of participants who achieve the following during treatment at Weeks 24, 48, and 96: •HDV RNA ≥2 log10 IU/mL decline from baseline or undetectable •HDV RNA
3. 3. • Change from baseline in liver stiffness as determined by transient elastography (e.g., FibroScan) at Weeks 24, 48, and 96 • Change from baseline in APRI (AST-to-platelet ratio index) at Weeks 24, 48, and 96
4. • Change from baseline in CTP score at Weeks 24, 48, and 96 in cirrhotic participants • Change from baseline in Model for End-Stage Liver Disease (MELD) score at Weeks 24, 48, and 96 in cirrhotic participants
5. • Proportion of participants with clinical disease progression from baseline in HDV-associated liver disease at Weeks 24, 48, and 96. Progression will be determined by the Independent Data Monitoring Committee (IDMC). Comparison with bulevirtide will include data through 48 weeks.
6. 4. Proportion of participants at Weeks 72 and 96 compared to those at Week 48 that achieve or maintain (defined as no change or improvement in) the below: • HDV RNA ≥2 log10 IU/mL decline from baseline or undetectable • HDV RNA
7. 5. Safety endpoints, defined above, will be compared between the first 48 weeks (Weeks 0-48) and the second 48 weeks (Week 48-96), including change in serum total bile acids.
8. 7. • Change from baseline in Chronic Liver Disease Questionnaire-HBV (CLDQ-HBV) and Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F) at Weeks 24, 48, and 96 • Compare change from baseline in CLDQ-HBV and FACIT-F between brelovitug and bulevirtide at Weeks 24 and 48, and at Week 48 (switch) and Week 96 (Arm 2)
9. 6. Proportion of participants who achieve HDV RNA

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Bluejay Therapeutics Inc.

Sponsor organisation

Bluejay Therapeutics Inc.

Address

400 Concar Drive Suite 03-101

City

San Mateo

Postcode

94402-2681

Country

United States

Scientific contact point

Organisation

Bluejay Therapeutics Inc.

Contact name

Nancy Schulman

Public contact point

Organisation

Bluejay Therapeutics Inc.

Contact name

Nancy Schulman

Third parties 13

Locations

8 EU/EEA countries · 47 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 88 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications