Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000997651
Ethics application status
Approved
Date submitted
15/06/2023
Date registered
13/09/2023
Date last updated
25/08/2024
Date data sharing statement initially provided
13/09/2023
Type of registration
Retrospectively registered

Titles & IDs
Public title
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
Scientific title
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
Secondary ID [1] 309911 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record
This study is extending ACTRN12621000592842 to investigate this drug in Chronic Hepatitis B (CHB) patients. Parts 1 and 2 of the study in healthy subjects investigated single and multiple doses. Part 3 (this study) in CHB patients will investigate multiple doses.

Health condition
Health condition(s) or problem(s) studied:
Chronic Hepatitis B 330379 0
Condition category
Condition code
Infection 327219 327219 0 0
Other infectious diseases
Oral and Gastrointestinal 327220 327220 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 326342 0
Treatment: Drugs
Comparator / control treatment
Two subjects in each cohort of 8 will receive matching placebo (water) administered orally in a syringe. Treatment assignments will be blinded.
Control group
Placebo

Outcomes
Primary outcome [1] 335105 0
Safety and tolerability of multiple doses of DF-006 in CHB patients will be assessed by collecting adverse events and monitoring lab results (hematology, biochemistry, coagulation and serum chemokine/cytokine), ECGs, and vital signs.

Adverse events will be initially reported based on subject reported events. These events will eventually be coded using MedDRA codes.
Timepoint [1] 335105 0
Safety and tolerability of multiple doses of DF-006 in CHB patients will be assessed as follows at the specified time points.

-Physical Examination, Vital Signs & ECG: Screening, Days -7, 1, 4 8, 11, 15, 22, 29, 36, 43 & 50
-Biochemistry/Hematology/Coagulation: Screening, Days -7, 1, 4, 8, 15, 22, 29, 36, 43 & 50
-Chemokine/Cytokine: Days 1, 4, 8, 11, & 15
-PBMC: Days 1 and 29
-Urinalysis: Screening, Days 1, 4, 8, 15, 22, 29, 36, 43 & 50
-Plasma PK: Day 1, 4 & 15
-Urine PK: Day 15
-HBV Genotype: Screening for HBV DNA, HBV RNA, HBeAg, HBsAg, HBcrAg, HBsAg Antibody, HBeAg Antibody: Screening, Day -7, 4, 8, 15, 22, 29, 36, 43 & 50
-Adverse Events: Continuous Assessment from the first dose of study drug until end of follow-up period after last dose of study drug. Subject follow-up will occur for 4 weeks after administration of the last dose of study drug.
Secondary outcome [1] 422998 0
To evaluate pharmacokinetics of multiple doses of DF-006 in CHB patients, the following parameters: AUC, Cmax, Cmin, T max, T1/2 . pharmacokinetics will be assessed using blood and urine samples.
Timepoint [1] 422998 0
Assessed on Day 1 ( Hours: -1, 1, 2) and once on Days 4,8,11,15,18,22,25,29,36,43,50 in all patients receiving multiple doses of study drug.
Secondary outcome [2] 422999 0
Blood biomarkers: Chemokine levels will be measured for changes over time. This will be assessed in all patients receiving multiple doses of study drug.
Timepoint [2] 422999 0
Assessed on Day 1 ( Hours: -1, 1, 2) and once on Days 4,8,11,15,18,22,25,29,36,43,50 in all patients receiving multiple doses of study drug.

Eligibility
Key inclusion criteria
1) 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.
2) 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.
3) 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.
4) 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.
5) Subjects must have a BMI of 18.0 to 35.0 kg/m^2.
6) Subjects must have CHB infection documented by serum HBsAg-positive at Screening and at least 6 months prior to Screening.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Evidence of clinically significant cardiac history
2) Personal or family history of chronic inflammatory skin disease or immune or autoimmune related disorders, diseases or syndromes
3) History or current evidence of use of amphetamines, barbiturates, narcotic or other drugs of abuse/recreational drug use, except under physician supervision
4) 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
5) Subjects with kidney disease or significant abnormal vital signs
6) 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
7) Subjects positive for anti-HBs
8) Subjects with any history or current evidence of hepatic decompensation
9) History or current evidence of hepatic decompensation, cirrhosis, liver fibrosis, or hepatocellular carcinoma
10) Subjects with liver disease of non-HBV etiology

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
Up to 15 cohorts of chronic hepatitis B subjects (5 cohorts for evaluation of virologically suppressed CHB subjects, 5 cohorts for evaluation of treatment naïve HBeAg-negative CHB subjects with abnormal ALT, and 5 cohorts for evaluation of treatment naïve HBeAg-positive CHB subjects with normal ALT) is considered sufficient to evaluate the safety and tolerability of DF-006 in the CHB subjects.

Continuous data will be summarized by descriptive statistics, including number of subjects, mean, standard deviation, median, and range. Categorical data will be summarized by the number and percentage of subjects.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/10/2023
Actual
19/07/2023
Date of last participant enrolment
Anticipated
30/08/2024
Actual
4/03/2024
Date of last data collection
Anticipated
31/12/2024
Actual
22/04/2024
Sample size
Target
120
Accrual to date
Final
26
Recruitment outside Australia
Country [1] 25594 0
New Zealand
State/province [1] 25594 0
Auckland
Country [2] 26525 0
Ukraine
State/province [2] 26525 0
Country [3] 26526 0
Moldova, Republic Of
State/province [3] 26526 0

Funding & Sponsors
Funding source category [1] 314092 0
Commercial sector/Industry
Name [1] 314092 0
Zhejiang Yao Yuan Biotechnology Ltd. (Drug Farm)
Country [1] 314092 0
China
Primary sponsor type
Commercial sector/Industry
Name
Zhejiang Yao Yuan Biotechnology Ltd. (Drug Farm)
Address
D7, 555 Chuangye RD, Dayun, Jiashan, Zhejiang 314100
Country
China
Secondary sponsor category [1] 316008 0
None
Name [1] 316008 0
Address [1] 316008 0
Country [1] 316008 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313232 0
Southern Health and Disability Ethics Committee
Ethics committee address [1] 313232 0
Ethics committee country [1] 313232 0
New Zealand
Date submitted for ethics approval [1] 313232 0
25/03/2021
Approval date [1] 313232 0
18/05/2021
Ethics approval number [1] 313232 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 127426 0
Prof Ed Gane
Address 127426 0
Auckland Clinical Studies (‘ACS’)
3 Ferncroft St, Grafton, Auckland 1010
Country 127426 0
New Zealand
Phone 127426 0
+64 9 3733479
Fax 127426 0
+64 9 3733479
Email 127426 0
[email protected]
Contact person for public queries
Name 127427 0
Christian Schwabe
Address 127427 0
Auckland Clinical Studies (‘ACS’)
3 Ferncroft St, Grafton, Auckland 1010
Country 127427 0
New Zealand
Phone 127427 0
+64 9 3733474
Fax 127427 0
+64 9 3733479
Email 127427 0
[email protected]
Contact person for scientific queries
Name 127428 0
Ed Gane
Address 127428 0
Auckland Clinical Studies (‘ACS’)
3 Ferncroft St, Grafton, Auckland 1010
Country 127428 0
New Zealand
Phone 127428 0
+64 9 3733479
Fax 127428 0
+64 9 3733479
Email 127428 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Specific IPD maybe shared with participants only upon request for that specific data by the study participant


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.