A Phase 1/2a, Randomized, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of BJT-778 in Healthy Volunteers and in Subjects with Chronic Hepatitis B Infection, Including Subjects with Chronic Hepatitis D Infection

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]

Decision date (initial)

2023-07-24

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Bluejay Therapeutics, Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Others, Safety

To evaluate the safety and tolerability of BJT-778

Secondary objectives 5

1. To evaluate the plasma pharmacokinetics (PK) of BJT-778
2. To evaluate the immunogenicity of BJT-778
3. To evaluate the anti-hepatitis B virus (HBV) activity of BJT-778
4. To evaluate the anti-hepatitis delta virus (HDV) activity of BJT-778
5. To evaluate the effect of BJT-778 on serum alanine aminotransferase (ALT) levels in subjects with chronic hepatitis delta (CHD) who have elevated baseline ALT levels

Conditions and MedDRA coding

Chronic Hepatitis B Infection

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Cohorts B through F: Able and willing to provide written informed consent (signed and dated) and any authorizations required by local law and can comply with all study requirements
2. Male or female adults between 18 and 70 years of age
3. BMI 18 to 40 kg/m2
4. Chronic HBV infection ≥6 months (eg, positive for serum HBsAg ≥6 months)
5. Plasma HBV deoxyribonucleic acid (DNA) <100 IU/mL at Scree
6. On nucleos(t)ide analogs (entecavir, tenofovir disoproxil, or tenofovir alafenamide) for at least 2 months and willing to remain on stable treatment for the duration of the study
7. Quantitative HBsAg level criteria at Screening by cohort/group: o Cohort B: ≥10 to ≤3000 IU/mL o Cohort C: >3000 IU/mL o Cohort D: ≥10 IU/mL o Cohorts E and F: ≥10 IU/mL
8. Females: Nonpregnant and nonlactating; surgically sterile (eg, tubal ligation, hysterectomy, bilateral salpingectomy, bilateral oophorectomy), postmenopausal (defined as 12 months of spontaneous amenorrhea in females >55 years of age or, in females ≤55 years of age, 12 months of spontaneous amenorrhea without an alternative medical cause and FSH levels in the postmenopausal range for the laboratory involved) or, if engaged in sexual relations and of childbearing potential, subject is using an acceptable contraceptive method from the time of signing the informed consent form until at least 12 weeks after the last dose of study drug.
9. Males: Surgically sterile or, if engaged in sexual relations with a female of childbearing potential, subject is utilizing an acceptable contraceptive method during treatment with study drug and for at least 12 weeks after the last dose of study drug. Agree not to donate sperm for at least 12 weeks after the last dose of study drug.
10. Cohorts D and F only: Must have quantifiable HDV ribonucleic acid (RNA) levels

Exclusion criteria 22

1. Cohorts B through F: Evidence of cirrhosis as determined by any of the following: o Liver biopsy (ie,Metavir Score F4) within 1 year of Screening, or o Fibroscan ≥10.8 Kpa within 1 year of Screening
2. History of decompensated liver disease as evidenced by ascites, hepatic encephalopathy, and/or gastric or esophageal varices
3. History of liver disease other than Hepatitis B (ie, nonalcoholic steatohepatitis, alcohol associated hepatitis, cholestatic liver disease, etc.)
4. Chronic HCV infection; subjects with past HCV RNA infection that was successfully treated must be HCV RNA negative and at least 24 weeks post-treatment
5. HIV infection (Cohorts B, C, and E); well-controlled HIV infection will be allowed in Cohorts D and F, defined as on antiretroviral therapy for at least 6 months and HIV RNA below the limit of quantification with a CD4 count ≥400 cells/mm3 at Screening
6. Received solid organ or bone marrow transplant
7. Currently taking, or took within 1 month of Screening, any immunosuppressive drugs (eg, prednisone). If the subject received a short course, the situation may be discussed with the Medical Monitor, or designee
8. Diagnosed hepatocellular carcinoma (HCC) or suspected HCC as evidenced by screening alpha-fetoprotein ≥20 ng/mL
9. History of hypersensitivity to any of the components in the BJT-778 formulation
10. Screening laboratory results as follows, or any other clinically significant abnormalities in screening laboratory values that would render a subject unsuitable for inclusion: o ALT or aspartate aminotransferase (AST) >3× upper limit of normal (ULN) o Total bilirubin >1.2× ULN, except for subjects with Gilbert’s (normal direct bilirubin) o Serum albumin <3.5 g/dL o International normalized ratio (INR) >1.2 o Platelet count <140 k/mm3 o Hemoglobin <12.0 g/dL for males and <11.0 g/dL for females o Absolute neutrophil count <1500/mm3 o Estimated glomerular filtration rate (eGFR) <50 mL/min/1.73 m2 by Modification of Diet in Renal Disease II o Positive test for blood on urinalysis. In the event of a positive test, eligibility may be confirmed with urine microscopy showing <5 red blood cells per high power field
11. Clinically significant abnormalities aside from chronic HBV infection in medical history (eg, previous acute coronary syndrome within 6 months of Screening, major surgery within 3 months of Screening, uncontrolled diabetes) or physical examination
12. History of bleeding diathesis or coagulopathy
13. History or suspected presence of vasculitis
14. History of extrahepatic disorders possibly related to HBV immune complexes (eg, glomerulonephritis, polyarteritis nodosa)
15. Malignancy within 5 years, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated
16. Treatment with a different investigational drug other than BJT-778, a biological agent or device within 4 weeks or 5 half-lives of Screening, whichever is longer
17. History of excess alcohol consumption within 1 year of Screening, defined as weekly intake of ≥14 drinks per week (average of ≥2 drinks per day)
18. History of drug abuse/addiction within 6 months of Screening (except cannabis) or a positive drug test at Screening (excluding physician-prescribed drugs and cannabis)
19. Unwillingness to comply with study procedures, including follow up, as specified by this protocol, or unwillingness to cooperate fully with the Investigator
20. Have any other conditions (medical, social, psychiatric, or other), which in the opinion of the Investigator would make the subject unsuitable for inclusion, or could interfere with the subject participating in or completing the study
21. Positive rapid antigen test for COVID-19 on Study Day 1
22. Cohorts B, C, and E only: Positive HDV Ab

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Incidence of treatment-emergent AEs and clinically significant laboratory abnormalities

Secondary endpoints 8

1. Determination of Cmax, Clast, Tmax, Tlast, AUCinf, AUClast, t1/2, λz, WF, and CL/F
2. Proportion of subjects who develop antidrug antibodies (ADAs) and, if detected, impact of ADAs on safety, PK, and pharmacodynamics
3. Maximum reduction of absolute HBsAg levels from baseline during treatment
4. Reductions of HBsAg from baseline over time
5. Maximum reduction of absolute HDV RNA levels from baseline
6. Reductions in HDV RNA from baseline over time
7. Proportion who achieves ≥2 log reduction in HDV RNA from baseline or HDV RNA undetectable
8. Maximum reduction of absolute ALT from baseline and changes of ALT from baseline over time in CHD subjects

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Bluejay Therapeutics Inc.

Sponsor organisation

Bluejay Therapeutics Inc.

Address

951 Mariners Island Boulevard Suite 300

City

San Mateo

Postcode

94404-1560

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 7

Locations

3 EU/EEA countries · 4 investigational sites

By country

Investigational sites

Application history

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