CompletedPhase 1ACTRN12623000997651

A Phase 1, Placebo-controlled, First-in-human Study of Orally Administered DF-006 to Evaluate the Safety, Tolerability, and Pharmacokinetics After Multiple Doses in Chronic Hepatitis B subjects

A Phase 1, Double-blind, Randomized, Placebo-controlled, First-in-human Study of Orally Administered DF-006 to Evaluate the Safety, Tolerability, and Pharmacokinetics After Multiple Doses of Orally Administered DF-006 in Chronic Hepatitis B Patients

Sponsor

Zhejiang Yao Yuan Biotechnology Ltd. (Drug Farm)

Enrollment

120 participants

Start Date

Jul 19, 2023

Study Type

Interventional

Conditions

Chronic Hepatitis B

Summary

Drug Farm is developing an investigational drug called DF-006, for treatment of Chronic Hepatitis B. DF-006 is a drug that attaches to a protein in the cell known as Alpha-1 kinase (ALPK1). In the liver, upon attaching to ALPK1, there is an activation of the body’s immune system that leads to the expression of many immune-related proteins known as chemokines and cytokines. These chemokines and cytokines are thought to play a role at various stages of hepatitis B virus (HBV) lifecycle, ultimately leading to reductions in viral (1) replication, (2) immunosuppressive proteins and, (3) genetic material. The study has three main aims: • To see if DF-006 is safe and well-tolerated in subjects with chronic hepatitis B • To measure levels of DF-006, and compounds related to DF-006, in the blood over time, following multiple doses of DF-006. • To assess the anti-viral effects of DF-006 subjects with chronic hepatitis B The study will also look at: • Whether or not ethnicity affects the levels of DF-006 in the blood. • Whether DF-006 is processed and cleared differently in people of Asian ethnicity. • If certain markers in the blood show that DF-006 is working as predicted.

Eligibility

Sex: Both males and femalesMin Age: 18 YearssMax Age: 65 Yearss

Inclusion Criteria6

Subject must sign an informed consent form (ICF) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study.
In the Investigator’s opinion, the subject is able to understand and comply with protocol requirements, instructions, and protocol stated restrictions and is likely to complete the study as planned.
Female subjects must NOT be of childbearing potential, which is defined as postmenopausal or permanently sterile, OR, if they are a woman of childbearing potential (WOCBP), must agree to use a condom and/or highly effective contraceptive therapy.
Male subjects must be either surgically sterile (eg, had a vasectomy), or otherwise incapable of fathering a child; OR, if non-sterile and heterosexually active, must have a partner who is postmenopausal, surgically sterile; OR, if their partner is WOCBP, must use highly effective methods of contraception from the time of male subject's Screening until at least 90 days after the last dose of study drug.
Subjects must have a BMI of 18.0 to 35.0 kg/m^2.
Subjects must have CHB infection documented by serum HBsAg-positive at Screening and at least 6 months prior to Screening.

Exclusion Criteria10

Evidence of clinically significant cardiac history
Personal or family history of chronic inflammatory skin disease or immune or autoimmune related disorders, diseases or syndromes
History or current evidence of use of amphetamines, barbiturates, narcotic or other drugs of abuse/recreational drug use, except under physician supervision
Excessive use of alcohol and unwilling to abstain from alcohol use for 48 hours prior to start of dosing through end of study follow-up
Subjects with kidney disease or significant abnormal vital signs
Female subjects who are pregnant, breastfeeding, or planning to become pregnant while on study medication or within 90 days after the last dose of study drug
Subjects positive for anti-HBs
Subjects with any history or current evidence of hepatic decompensation
History or current evidence of hepatic decompensation, cirrhosis, liver fibrosis, or hepatocellular carcinoma
Subjects with liver disease of non-HBV etiology

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Interventions

This is a double-blind, randomized, placebo-controlled, multiple-ascending doses (MAD) study that will be conducted in up to 120 chronic hepatitis B (CHB) subjects. Hepatitis B e-antigen (HBeAg)-negative virologically suppressed (VS), HBeAg-negative treatment naïve (TN), or currently untreated (CU) CHB subjects with abnormal serum alanine aminotransferase (ALT), and HBeAg-positive TN or CU CHB subjects with normal serum ALT will be evaluated in separate MAD cohorts of up to 40 subjects each. This study will investigate the safety, tolerability, PD, and antiviral activity of once weekly (QW) oral (PO) doses of DF-006 for 4 weeks. Subject follow-up will occur for 4 weeks after administration of the last dose of study drug. Subsequent cohort dosage (multiple-ascending doses) and dosing frequency will be based on Dose Selection Guidelines and prior cohort CHB subject data. Three cohorts of HBeAg-negative VS CHB subjects of 8 subjects each (24 subjects in total), and up to 2 optional cohorts of 8 subjects each (16 subjects in total), will receive once QW PO doses of DF-006 or matching placebo for a duration of 4 weeks. Within each cohort, 6 subjects will be randomly assigned to receive DF-006, and 2 subjects will receive matching placebo. Three cohorts of HBeAg-negative TN/CU CHB subjects with abnormal serum ALT of 8 subjects each (24 subjects in total), and up to 2 optional cohorts of 8 subjects each (16 subjects in total) will receive PO QW doses of DF-006 or matching placebo for a duration of 4 weeks. Within each cohort, 6 subjects will be randomly assigned to receive DF-006, and 2 subjects will receive matching placebo. Three cohorts of HBeAg-positive TN/CU CHB subjects with normal serum ALT of 8 subjects each (24 subjects in total), and up to 2 optional cohorts of 8 subjects each (16 subjects in total), will receive PO QW doses of DF-006 or matching placebo for a duration of 4 weeks. Within each cohort, 6 subjects will be randomly assigned to receive DF-006, and 2 subjects will receive matching placebo. The starting dose for Part 3 is 0.4 mcg PO QW for 4 weeks. This dose was selected by a Study Safety Committee following a review of all the preliminary blinded the safety data from Parts 1 and 2 of this study.