A study to understand the safety and effectiveness of an investigational drug called Selgantolimod in combination with other drugs for the treatment of long term hepatitis B infectio

Phase 1

• Conditions: Chronic Hepatitis B (CHB); MedDRA version: 20.1Level: PTClassification code 10008910Term: Chronic hepatitis BSystem Organ Class: 10021881 - Infections and infestations; Therapeutic area: Diseases [C] - Virus Diseases [C02]

• Registration Number: EUCTR2021-000672-11-DK
• Lead Sponsor: Gilead Sciences, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-10-06
• Last Update Posted: 19 August 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

1. Must have the ability to understand and sign a written informed consent form (ICF), which must be obtained prior to initiation of study procedures
2. Adult male and nonpregnant, nonlactating female participants, 18 to 65 years (19-65 years of age in Republic of Korea) of age inclusive based on the date of the screening visit
3. Documented evidence of chronic HBV infection (eg, HBsAg positive for more than 6 months) with detectable HBsAg levels (> 1.5 log10 IU/mL) at screening
4. Screening electrocardiogram (ECG) without clinically significant abnormalities and with QTcF interval (QT corrected using Fridericia’s formula) = 450 msec for males and = 470 msec for females.
5. Females of childbearing potential (as defined in Appendix 4 of the protocol must have a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline prior to enrollment
6. Male and female participants of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception as described in Appendix 4 of the protocol. Must be willing and able to comply with all study requirements.

Participants in Cohort 1 should meet the following additional criteria to be eligible to participate in this study:
7. Have been on a commercially available HBV NUC treatment(s) (ie, TAF, TDF, entecavir, adefovir, lamivudine, telbivudine, either as single agents or in combination) with no change in regimen for 3 months prior to screening and willing to initiate TAF 25 mg.
8. Have a historical HBV DNA < LLOQ, measured at least once at local laboratory, 6 or more months prior to screening.
9. HBV DNA < LLOQ by central laboratory at screening

Participants in Cohort 2 and 3 should meet the following additional criterion at screening to be eligible to participate in this study:
10. HBV DNA > 2000 IU/mL (HBeAg-negative) and HBV DNA > 20,000 IU/mL (HBeAgpositive)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 115
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion Criteria

1. Extensive bridging fibrosis or cirrhosis as defined clinically by any 1 of the following:
a) Metavir = 3 or Ishak fibrosis score = 4 by a liver biopsy within 1 year of screening, or, in the absence of an appropriate liver biopsy, either:
b) Screening FibroTest score of > 0.48 and AST to platelet ratio index (APRI) > 1 by central laboratory, or
c) Historical (within = 6 months of screening) or current FibroScan with a result > 9 kPa
If liver biopsy is available, the liver biopsy result supersedes (b) and/or (c, if available)
If an appropriate liver biopsy is not available, fibrosis will be evaluated by (b) and/or (c, if available). In the event of discordance between (b) and (c), the FibroScan results will take precedence.
2. Participants meeting any of the following laboratory parameters at screening:
a) Hemoglobin < 12 g/dL (for males) or < 11 g/dL (for females)
b) White blood cell (WBC) count < 2500 cells/mm3
c) Neutrophil count < 1500 cell/mm3 (or < 1000 cell/mm3 if considered a physiological variant in a participant of African descent)
d) ALT = 2 x ULN (Cohort 1 only), ALT > 5 x ULN (Cohorts 2 and 3)
e) International normalized ratio (INR) > ULN unless the participant is stable on an anticoagulant regimen affecting INR
f) Albumin < 3.5 g/dL
g) Direct bilirubin > 1.5 x ULN
h) Platelet Count < 100,000/µL
i) Positive autoantibodies, defined as any one or more of the following:
i. Antinuclear antibodies (ANA) > 1:80
ii. Smooth muscle antibodies (anti-SMA) > 1:80
iii. Antimitochondrial antibodies (AMA) > 1:40
iv. Anti-thyroid peroxidase (anti-TPO) > 35 IU/mL
j) Estimated creatinine clearance (CLcr) < 60 mL/min (using the Cockcroft-Gault method) based on serum creatinine and actual body weight as measured at the screening evaluation, ie,
Male: ((140 – Age [years]) x (Weight [kg])) / (72 x (Serum Creatinine [mg/dl])) = CLcr (mL/min)
Female: ((140 – Age [years]) x (Weight [kg])) x 0.85 / (72 x (Serum Creatinine [mg/dL])) = CLcr (mL/min)
3. Participants in Cohort 2 and 3: Received OAV treatment for HBV within 6 months of screening. Participants who meet criteria for initiation of NUC treatment as judged by the principal investigator (PI) during screening should be excluded from Cohorts 2 and 3.
4. Co-infection with HIV, HCV, or hepatitis D virus (HDV). Participants who are HCV Ab or HDV Ab positive, but have a documented negative HCV RNA or HDV RNA, respectively, are eligible.
5. Current or prior history of HCC (eg, as evidenced by prior imaging) or screening a-fetoprotein = 50 ng/mL without imaging to rule out HCC
6. Current or prior history of clinical hepatic decompensation (eg, ascites, encephalopathy, or variceal hemorrhage).
7. Malignancy within 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection (eg, basal cell skin cancer). Participants under evaluation for possible malignancy are not eligible
8. Significant cardiovascular, ophthalmological, pulmonary, or neurological disease in the opinion of the investigator
9. Diagnosis of any autoimmune disease (eg, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, ulcerative colitis, pneumonitis, autoimmune hepatitis, sarcoidosis, psoriasis of greater than mild severity, autoimmune uveitis, autoimmune nephritis, thyroiditis), poorly controlled diabetes mellitus, significant psychiatric illness, severe chronic obstructive pulmonary disease (COPD), hemoglobinopathy, retinal disease, or are immunosuppressed
10.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified