Phase 3 Study to Evaluate Brelovitug vs Delayed Treatment for Treatment of Chronic Hepatitis Delta Infection (AZURE-4)

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

2 Feb 2026 → ongoing

Decision date (initial)

2025-12-22

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Bluejay Therapeutics, Inc.

External identifiers

EU CT number

2025-522105-38-00

WHO UTN

U1111-1324-0622

ClinicalTrials.gov

NCT07298330

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Safety, Efficacy, Others, Pharmacokinetic, Therapy

To evaluate the efficacy of brelovitug at Week 24 compared with delayed treatment on CHD at Week 12.

Secondary objectives 4

1. To evaluate the safety and tolerability of chronic treatment with brelovitug and in comparison to 12-week delayed treatment.
2. To characterize the efficacy of chronic treatment with brelovitug and in comparison to Week 12 delayed treatment on HDV.
3. To evaluate the HDV clearance rates after 96 weeks of treatment in subjects who do not rollover to the extended treatment protocol
4. To evaluate the effect of chronic treatment with brelovitug on HDV disease progression, including assessment of HDV-related liver disease progression

Conditions and MedDRA coding

Chronic Hepatitis Delta Infection

Study design 4 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 1. Willing and able to provide written informed consent.
2. 2. Male or female, ≥18 years of age at Screening.
3. 3. Confirmation of chronic HDV infection, defined as positive for anti-HDV antibody test or HDV RNA for 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. 4. HDV RNA >500 IU/mL at Screening.
5. 5. ALT >ULN at Screening.
6. 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.
7. 7. In countries where HDV treatment is approved and available, participants must be documented as unwilling or unable to receive treatment.

Exclusion criteria 15

1. 1. Pregnant or nursing females.
2. 9.Treatment with another investigational drug, a biological agent, or device within 4 weeks or 5 half-lives, whichever is longer, of Baseline.
3. 10. Use of any interferon within 12 weeks of Screening.
4. 11. Use of any prohibited concomitant medications as described in Study Protocol.
5. 12. Regular alcohol misuse, defined as weekly intake of ≥14 alcoholic drinks per week (average of ≥2 alcoholic drinks per day) within 12 months of Screening.
6. 13. Clinically relevant drug abuse (not including cannabis) within 12 months of Screening.
7. 14. Unwillingness to comply with study procedures as specified by this protocol, or unwillingness to cooperate fully with the Investigator.
8. 15. 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.
9. 2. Male or female participants of childbearing potential unwilling to comply with contraception requirements during the study.
10. 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 of acute decompensation 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 forced expiratory volume 1 second (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).
11. 4. CTP >6 (B or C)
12. 5. Presence of other liver disease(s) (non-HBV/HDV), such as metabolic dysfunction-associated steatohepatitis (MASH), alcohol associated hepatitis, cholestatic liver disease, other viral (e.g., HCV or HAV) 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 was successfully treated (HCV RNA negative) ≥6 months prior to Screening.
13. 6. Uncontrolled human immunodeficiency virus (HIV) infection defined as having quantifiable HIV RNA levels in the blood at Screening.
14. 7. History of hypersensitivity to any of the components in the brelovitug formulation.
15. 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 Crockcroft-Gault (CrCl) <30 mL/min d) Alpha fetoprotein (AFP) >100 ng/mL

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The proportion of participants who achieve a composite endpoint of virologic response and ALT normalization at Week 24 in brelovitug arms will be compared to response at Week 12 of delayed-treatment arm: • Virologic response is defined as HDV RNA ≥2 log10 IU/mL decrease from Baseline or undetectable HDV RNA • ALT normalization is defined as a decrease in ALT from Baseline to ≤ULN.

Secondary endpoints 8

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 delayed treatment will include data through Week 12 (Predose).
2. The proportion of participants who achieve the following at Week 24, 48, and 96 of treatment unless otherwise specified: • Virologic response defined as ≥2 log10 IU/mL decline from baseline or undetectable HDV RNA • HDV RNA
3. Proportion of subjects who achieve HDV RNA
4. Change from Baseline in liver stiffness as determined by transient elastography at Weeks 24, 48, and 96 of brelovitug treatment
5. Change from Baseline in AST-to-platelet ratio index (APRI) at Weeks 24, 48, and 96 of brelovitug treatment
6. Change from Baseline in CTP score in cirrhotic participants at Weeks 24, 48, and 96 of brelovitug treatment
7. Change from Baseline in Model for End-Stage Liver Disease (MELD) score in cirrhotic participants at Weeks 24, 48, and 96 of brelovitug treatment
8. Proportion of participants with clinical disease progression from Baseline in HDV-associated liver disease at Weeks 24, 48 and 96 of brelovitug treatment. Progression will be determined by the Independent Data Monitoring Committee (IDMC).

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Bluejay Therapeutics Inc.

Sponsor organisation

Bluejay Therapeutics Inc.

Address

255 Shoreline Drive Suite 450

City

Redwood City

Postcode

94065-1450

Country

United States

Scientific contact point

Organisation

Bluejay Therapeutics Inc.

Contact name

Nancy Shulman

Public contact point

Organisation

Bluejay Therapeutics Inc.

Contact name

Nancy Shulman

Third parties 10

Locations

3 EU/EEA countries · 6 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 38 files

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

Application history

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