Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000592842
Ethics application status
Approved
Date submitted
31/03/2021
Date registered
18/05/2021
Date last updated
27/10/2023
Date data sharing statement initially provided
18/05/2021
Type of registration
Prospectively 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 a Single Dose and Multiple Doses in Healthy 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 a Single Dose and Multiple Doses of Orally Administered DF 006 in Healthy Subjects (Part 1 and Part 2)
Secondary ID [1] 303815 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Hepatitis B 321320 0
Condition category
Condition code
Infection 319112 319112 0 0
Other infectious diseases
Oral and Gastrointestinal 319511 319511 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
Healthy subjects in Part 1 will receive a single oral liquid dose of DF-006, starting at 3mcg, for one day. Subsequent doses will be based on safety data from prior patients and cohorts.
Healthy subjects in Part 2 will receive a single oral liquid dose of DF-006 weekly for 14 days, starting at the dose determined in Part 1. Participants in Part 2 are likely to be different from participants in Part 1.
A Study Safety Committee will provide safety oversight and will follow Dose Selection Guidelines to determine cohort doses. Cohort progression will be based on Data Review Meetings. In Part 1, cohort progression will occur approximately every 3 weeks. In Part 2, cohort progression will occur approximately every 4 weeks. Adherence to the intervention will be monitored by direct observation of dosing.
Intervention code [1] 320120 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] 326999 0
Safety and tolerability of DF-006 by collecting adverse events, and monitoring lab results (hematology, biochemistry, coagulation and serum chemokine/cytokine), ECGs, and vital signs. Adverse event will be initially reported based on subject reported events. These events will eventually be coded using MedDRA codes.
Timepoint [1] 326999 0
Part 1:
-Physical Examination, Vital Signs & ECG: Screening, Day -1 to Day 5
-Holter Monitoring: Day 1 & 2
-Biochemistry/Hematology/Coagulation: Screening, Day -1 to Day 5
-Chemokine/Cytokine: Day 1 & 2
-PBMC: Day 1 and 2
-Urinalysis: Screening, Day -1 to Day 5
-Plasma PK: Day 1 & 2
-Adverse Events: Continuous Assessment

Part 2:
-Physical Examination, Vital Signs & ECG: Screening, Day -1 to Day 28
-Biochemistry/Hematology/Coagulation: Screening, Day -1 to Day 28
-Chemokine/Cytokine: Day 1, 2, 7 and 15
-PBMC: Day 1 and 15
-Urinalysis: Screening, Day -1 to Day 28
-Plasma PK: Day 1, 2, 7 and 15
-Urine PK: Day 15
-Adverse Events: Continuous Assessment

Part 3:
-Physical Examination, Vital Signs & ECG: Screening, Day -7, 1, 2, 8, 15, 22, 29, 36, 43 & 50
-Biochemistry/Hematology/Coagulation: Screening, Day -7, 1, 2, 8, 15, 22, 29, 36, 43 & 50
-Chemokine/Cytokine: Day 1 & 15
-PBMC: Day 1 and 15
-Urinalysis: Screening, Day 1, 2, 8, 15, 22, 29, 36, 43 & 50
-Plasma PK: Day 1, 2 & 15
-Urine PK: Day 15
-HBV Genotype: Screening
-HBV DNA, HBV RNA, HBeAg, HBsAg, HBcrAg, HBsAg Antibody, HBeAg Antibody: Screening, Day -7, 2, 8, 15, 22, 29, 36, 43 & 50
-Adverse Events: Continuous Assessment
Secondary outcome [1] 393416 0
To evaluate pharmacokinetics using the following parameters: AUC, Cmax, Cmin, T max, T1/2 . pharmacokinetics will be assessed using blood and urine samples.
Timepoint [1] 393416 0
For Part 1: assessed on Day 1 (Hours: -1, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8) and once on Day 2
For Part 2: assessed on Day 1 (Hours: -1, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12) and once on Days 2, 7 and 14
Secondary outcome [2] 394875 0
Blood biomarkers: Chemokine levels will be measured for changes over time,
Timepoint [2] 394875 0
For Part 1: assessed on Day 1 (Hours: -1, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8) and once on Days 2
For Part 2: assessed on Day 1 (Hours: -1, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12) and once on Days 2, 7 and 14
Secondary outcome [3] 395332 0
Blood biomarkers: Cytokine levels will be measured for changes over time,
Timepoint [3] 395332 0
For Part 1: assessed on Day 1 (Hours: -1, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8) and once on Days 2
For Part 2: assessed on Day 1 (Hours: -1, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12) and once on Days 2, 7 and 14
Secondary outcome [4] 428285 0
Markers of antiviral activity: HBV DNA, HBV RNA, HBeAg, HBsAg, HBcrAg, HBsAg Antibody, HBeAg Antibody
Timepoint [4] 428285 0
Screening, Days -7, 4, 8, 15, 22, 29, 36, 43 & 50

Eligibility
Key inclusion criteria
Female subjects must have a negative serum pregnancy test and must not be of childbearing potential
Male subjects must be either surgically sterile, or incapable of fathering a child, or have a heterosexual partner partner who is not pregnant or of childbearing potential
Nonsmoker within last 3 months
BMI of 18.0 to 32.0 kg/m2
Subjects must be deemed healthy by the Investigator on the basis of a medical evaluation
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
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 current hepatitis A, B, C, D, E, HIV, infection or acute infection such as SARS-CoV-2 (COVID-19)
Subjects with kidney disease or significant abnormal vital signs

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)
Central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised 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
The proposed sample sizes for each study part are typical for studies at this phase of development and are deemed sufficient to evaluate the study objectives for this Phase 1 study. In Part 1, 5 cohorts, each with 8 participants were evaluated. In Part 1, it was determined that only 5 cohorts were necessary to understand the safety, pharmacokinetics and pharmacodynamics of DF-006 based on the review of data from Cohort 1-4. In Part 2, there is one planned and one optional cohort, each with 8 participants.
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
3/08/2022
Actual
16/07/2021
Date of last participant enrolment
Anticipated
30/08/2024
Actual
11/10/2022
Date of last data collection
Anticipated
31/12/2024
Actual
30/11/2022
Sample size
Target
34
Accrual to date
Final
50
Recruitment outside Australia
Country [1] 23568 0
New Zealand
State/province [1] 23568 0
Auckland
Country [2] 25894 0
Korea, Republic Of
State/province [2] 25894 0
Country [3] 25926 0
Korea, Republic Of
State/province [3] 25926 0

Funding & Sponsors
Funding source category [1] 308213 0
Commercial sector/Industry
Name [1] 308213 0
Zhejiang Yao Yuan Biotechnology Ltd. (Drug Farm)
Country [1] 308213 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] 308998 0
None
Name [1] 308998 0
Address [1] 308998 0
Country [1] 308998 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308194 0
Southern Health and Disability Ethics Committee
Ethics committee address [1] 308194 0
Ethics committee country [1] 308194 0
New Zealand
Date submitted for ethics approval [1] 308194 0
25/03/2021
Approval date [1] 308194 0
18/05/2021
Ethics approval number [1] 308194 0

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

Contacts
Principal investigator
Name 109882 0
Prof Ed Gane
Address 109882 0
Auckland Clinical Studies (‘ACS’)
3 Ferncroft St, Grafton, Auckland 1010

Country 109882 0
New Zealand
Phone 109882 0
+64 9 3733474
Fax 109882 0
+64 9 3733479
Email 109882 0
[email protected]
Contact person for public queries
Name 109883 0
Christian Schwabe
Address 109883 0
Auckland Clinical Studies (‘ACS’)
3 Ferncroft St, Grafton, Auckland 1010

Country 109883 0
New Zealand
Phone 109883 0
+64 9 3733474
Fax 109883 0
+64 9 3733479
Email 109883 0
[email protected]
Contact person for scientific queries
Name 109884 0
Ed Gane
Address 109884 0
Auckland Clinical Studies (‘ACS’)
3 Ferncroft St, Grafton, Auckland 1010

Country 109884 0
New Zealand
Phone 109884 0
+64 9 3733474
Fax 109884 0
+64 9 3733479
Email 109884 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.