A Global, Randomized, Open-label, Multicenter, Phase 2b/3 Trial Evaluating BJT-778 vs Delayed Treatment for the Treatment of Chronic Hepatitis Delta Infection (AZURE-1)

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

24 Jun 2025 → ongoing

Decision date (initial)

2025-06-17

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: Pharmacokinetic, Efficacy, Safety, Others

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

Secondary objectives 6

1. To evaluate the efficacy of brelovitug on CHD compared with pre-specified performance goal of 40% at Week 24.
2. To evaluate the safety and tolerability of chronic treatment with brelovitug and in comparison, to delayed treatment.
3. To characterize the efficacy of brelovitug and in comparison, to delayed treatment.
4. To compare the efficacy of brelovitug 900 mg (Arm 2) to 300 mg (Arm 1) treatment regimen.
5. To evaluate the effect of brelovitug on HDV disease progression, including assessment of HDV-related liver disease progression.
6. To evaluate the rate of undetectable HDV RNA after treatment in participants who do not rollover to the long-term treatment protocol

Conditions and MedDRA coding

Chronic Hepatitis Delta 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 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. 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 14

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 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).
4. CTP >6 B or C.
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 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.
6. Uncontrolled human immunodeficiency virus (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 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 Crockcroft-Gault (CrCl) <30 mL/min, d) Alpha fetoprotein (AFP) >100 ng/mL.
9. Treatment with another investigational drug, a biological agent, or device within 4 weeks or 5 half-lives, whichever is longer, of Baseline.
10. Use of any prohibited concomitant medications as described in Section 7.7.
11. 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.
12. Clinically relevant drug abuse (not including cannabis) within 12 months of Screening.
13. Unwillingness to comply with study procedures as specified by this protocol, or unwillingness to cooperate fully with the Investigator.
14. 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 of virologic response and ALT normalization. • Virologic response is defined as HDV RNA ≥2 log10 IU/mL decrease from Baseline or undetectable HDV RNA (< lower limit of quantification [LLOQ], target not detected [TND]),• ALT normalization is defined as a decrease in ALT from Baseline to ≤UNL. • The primary efficacy analysis will be tested according to the hierarchical testing.

Secondary endpoints 7

1. The proportion of participants who achieve a composite endpoint of virologic response and ALT normalization. • Virologic response is defined as HDV RNA ≥2 log10 IU/mL decrease from Baseline or undetectable HDV RNA (< lower limit of quantification [LLOQ], target not detected [TND]),• ALT normalization is defined as a decrease in ALT from Baseline to ≤UNL. • The primary efficacy analysis will be tested according to the hierarchical testing.
2. 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.
3. The proportion of participants who achieve the following during treatment: • Virologic response defined as ≥2 log10 IU/mL decline from baseline or undetectable HDV RNA • HDV RNA
4. The proportion of participants who achieve a composite endpoint at Weeks 24, 48, and 96.
5. • Change from Baseline in liver stiffness as determined by transient elastography (e.g., FibroScan) at Weeks 24, 48, 96, 120 (Arm 3). • Change from Baseline in APRI at Weeks 24, 48, 96, 120 (Arm 3). • Change from Baseline in CTP score at Weeks 24, 48, 96, and 120 (Arm 3) in cirrhotic participants. • Change from Baseline in MELD score at Weeks 24, 48, 96, 120 (Arm 3) in cirrhotic participants.
6. • Proportion of participants with clinical disease progression from Baseline in HDV-associated liver disease at Weeks 24, 48, 96, 120 (Arm 3). Progression will be determined by the IDMC.
7. Proportion of participants who achieve HDV RNA

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

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 11

Locations

1 EU/EEA country · 3 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 14 files

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

Application history

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