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Trial registered on ANZCTR


Registration number
ACTRN12619001443189
Ethics application status
Approved
Date submitted
1/08/2019
Date registered
17/10/2019
Date last updated
2/03/2020
Date data sharing statement initially provided
17/10/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase I clinical trial to evaluate the safety and pharmacokinetics of SHR0302 base ointment at single dose and multiple dose in healthy adult subjects
Scientific title
A Phase I clinical trial to evaluate the safety and pharmacokinetics of SHR0302 base ointment at single dose and multiple dose in healthy adult subjects
Secondary ID [1] 298736 0
None
Universal Trial Number (UTN)
U1111-1237-0058
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Atopic dermatitis 313675 0
Condition category
Condition code
Skin 312088 312088 0 0
Dermatological conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study will compare two active doses of 1% and 2% SHR0302 to placebo. Part 1 is a randomized, double-blind, vehicle-controlled, single ascending dose trial; it is planned to enroll 32 healthy adult subjects. Part 1 includes a screening period (D-28~D-2), baseline period (D-1), dosing period (D1), observation period (D2~D3), and follow-up period (D4~D7). A total of 4 doses are designed for the single ascending dose study which is carried out in 4 cohorts. Each cohort will be a single dose with one application on Day 1. The 4 dose groups are 1% SHR0302 base ointment applied to 5% Body Surface Area (BSA), 1% SHR0302 base ointment applied to 10% BSA, 2% SHR0302 base ointment applied to 10% BSA, and 2% SHR0302 base ointment applied to 20% BSA. The ointment will be applied to a different % of body surface area (BSA) depending on the cohort.
Intervention code [1] 315013 0
Treatment: Drugs
Comparator / control treatment
Placebo group with vehicle ointment only. In Part 1 each cohort will be dosed at a ratio of 6:2 active: placebo.
Control group
Placebo

Outcomes
Primary outcome [1] 320738 0
To evaluate the safety and tolerability of 1% and 2% SHR0302 base ointment in a single topical dose in healthy adult subjects.
Timepoint [1] 320738 0
Vital signs: collect systolic pressure and diastolic pressure (sitting), body temperature, heart rate, respiration after at least 5 min of rest. The timing of vital signs measurement on Day 1 will be 0.5h pre-dose, and 2, 4, 12 and 24 h after administration.

Physical Exam: collected at screening, Day -1, and Day 3 post IP administration.

Adverse Events: collected from the start of dosing to completion of final follow up. AEs will be assessed at Day -1, Day 1 during dosing and at all FU (Day 5 and Day 8 post dose) visits after dosing. There are no known AEs expected but skin will be assessed for any irritation throughout each visit.
Secondary outcome [1] 372662 0
To evaluate the pharmacokinetics of 1% and 2% SHR0302 base ointment in a single or multiple topical dose in healthy adult subjects. The plasma drug concentration and PK parameters of SHR0302 after single topical dose, including but not limited to: AUC(0-t), AUC(0-24), Cmax, Tmax, CL/F, Vz/F and half-life (t1/2). No exploratory PK analysis will be undertaken.
Timepoint [1] 372662 0
Plasma samples for PK analysis are collected within 1 h before dosing on D1, at 0.5, 1, 2, 4, 6, 8, 12h (±10 min for all) and 24, 36, 48, 96 and 168h (±30 min for all) after dosing for Part 1.

Eligibility
Key inclusion criteria
1. Healthy adult subjects between 18-55 years of age (inclusive), male or female, at the time of informed consent.
2. The body mass index (BMI equal to body mass/square of body height) of the subjects ranges from 19 to 26 kg/m2 (inclusive), and males of weight less than or equal to 50 kg, females of weight less than or equal to 45 kg.
3. The overall health is good at screening, as determined by medical history, physical examination, vital signs, laboratory examination, 12-lead electrocardiogram (ECG) and chest X-ray at screening.
4. All women of childbearing potential who are not in same-sex relationships and all men with female partner of childbearing potential must be willing to use effective method of contraception from signing of informed consent form, throughout the duration of the study, and for 1 month after last dose of study medication. The subjects understand and comply with the study requirements, voluntarily participate in the study and sign the informed consent form.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Subjects presenting with any of the following items will not be enrolled in this study:
1. Currently having or have a history of any of the following diseases:
1) Suspected allergy to the study drug or any component of the study drug, or allergy constitution;
2) Have a history of malignant tumor;
3) Skin injuries or abnormalities that might affect the evaluation of study drug application site, such as dermatitis, tattoo, scar, excessive hair, birthmark, injury, uneven skin color, sunburn, etc.;
4) In the opinion of the investigator, any clinically relevant skin diseases that are contraindicated in the study or affect the evaluation of application site, including psoriasis, eczema, acne, atopic dermatitis, dysplastic nevus, or other skin lesions, or a history of skin cancer;
5) Subjects with a history of herpes simplex or herpes zoster;
6) Subjects who currently have thyroid disorders (including hyperthyroidism, hypothyroidism, or are currently receiving thyroid replacement therapy. Subjects with abnormal TSH, fT4, and fT3 values on blood tests at screening must be excluded;
7) Subjects who have received any surgical operation within 3 months prior to screening or plan to receive the operation during the study and within 1 month after completing all study visits;
8) Subjects with a history of clinical major heart disease, liver disease, nerve disease, respiratory disease, blood disease, digestive disease, immune disease, kidney disease or mental disease, which is considered by the investigator to confuse the study results or affect absorption, distribution, metabolism and excretion of drug or place the subjects at improper risks;
9) Clinical symptoms, signs, laboratory examination or chest X-ray indicate active tuberculosis;
10) Subjects who have the investigator-judged clinically significant infections within 1 months prior to screening, including acute and chronic infections such as abscess, furuncle, carbuncle, respiratory tract infection, urinary and reproductive infection, and systematic infections, etc.
2. Subjects who are using or have a history of using any of the following drugs:
1) Subjects who are unable to discontinue CYP3A inducer or CYP3A inhibitor 2 weeks prior to the baseline visit and during the study;
2) Subjects who have inoculated any live vaccine within 1 month before screening or need to inoculate live vaccine during the study (including 30 days after the last dose of study drug);
3) Prescription drugs are used within 14 days before baseline;
4) OTC drugs are used within 14 days before baseline, including natural health products (e.g. food supplement and herbal supplement), with the exception of occasional use of paracetamol (up to 2 g per day);
5) Topical skin products (including sun-screening agents, moisturizers, cosmetics, insect repellents, creams, powders, lotions, sprays or gels) are used within 48 hours before baseline;
6) Topical skin drugs (e.g., topical hormones, vitamin A) are used at the study application site within 21 days before baseline
3. Any of the following laboratory endpoints meet the following criteria at screening or baseline examination:
1) The ECG shows QTc greater than 450 ms or any other obvious abnormality, which is determined as clinically significant by the investigator;
2) Blood routine examination shows that the white blood count, neutrophil count, lymphocyte count, or hemoglobin exceed the normal reference range and is clinically significant as determined by the investigator;
3) Alanine aminotransferase (ALT) greater than 1.5×ULN and/or aspartate transaminase (AST) greater than 1.5×ULN and/or bilirubin greater than 1.5×ULN;
4) Estimated glomerular filtration rate (eGFR) calculated by MDRD formula <90 mL/min/1.73 m²;
5) Hepatitis B surface antigen, hepatitis B e antigen, tuberculosis testing (T-SPOT TB/QuantiFERON TB), anti-hepatitis C virus antibody, HIV antibody and syphilis antibody positive;
Other laboratory findings which exceed the normal reference range, based on which the investigator determines that the subject is not suitable to participate in this study.
4. General conditions:
1) Subjects with childbearing or sperm donation plan during the study period or within 1 month after the last dose of study drug;
2) Smokers: Over 5 cigarettes per day on average;
3) Drinkers: Alcohol test positive; or long-term drinking over the past 3 months, with the total amount consumed per week by male subjects exceeding 3,465 mL of beer, 1,750 mL of wine, yellow or low-alcohol liquor, or 525 mL of high-alcohol liquor (greater than 40 degrees);
4) Drug abusers: Judged by urine test positive;
5) Women who are pregnant or breastfeeding;
6) Subjects who have donated blood and the blood volume less than or equal to 400 mL, or received infusion of any blood product within 3 months before screening;
7) Subjects who have participated in the clinical trial of any drug or medical device within 3 months before screening.

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)
sealed opaque envelopes
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
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Part 1 has four cohorts, among which, cohorts 1-2 randomly receive 1% SHR0302 base ointment or vehicle, and cohort 3-4 randomly receive 2% SHR0302 base ointment or vehicle. Each treatment group goes through screening period (maximum 28 days), single dosing period (1 day), observation period (2 days for safety evaluation) and follow-up period (7 days after administration). The expected longest duration for each subject in Part 1 is 36 days.
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
Descriptive statistics of binary endpoints will include number of subjects and percentage. The PK endpoints (plasma drug concentration and parameters) will be summarized using geometric mean, geometric coefficient of variation, mean, standard deviation, median, maximum and minimum, etc. Demographics and baseline characteristics will be summarized and listed.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
28/10/2019
Date of last participant enrolment
Anticipated
2/12/2019
Actual
9/12/2019
Date of last data collection
Anticipated
24/12/2019
Actual
17/12/2019
Sample size
Target
32
Accrual to date
Final
32
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 14236 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 27229 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 303291 0
Commercial sector/Industry
Name [1] 303291 0
Reistone Biopharma Co., Ltd.
Country [1] 303291 0
China
Primary sponsor type
Commercial sector/Industry
Name
Reistone Biopharma Co., Ltd.
Address
No. 800 Naxian Road,
Building 1, #402-5, Zhangjiang High-tech Park, Pudong, 201210, Shanghai, China 201210
Country
China
Secondary sponsor category [1] 303324 0
Commercial sector/Industry
Name [1] 303324 0
Atridia Pty Ltd (Australia)
Address [1] 303324 0
Suite2.02, 46 Market St, Sydney NSW 2000, AUSTRLIA
Country [1] 303324 0
Australia
Secondary sponsor category [2] 303508 0
Commercial sector/Industry
Name [2] 303508 0
IQVIA RDS Pty. Limited
Address [2] 303508 0
8/201 Pacific Hwy, St Leonards NSW 2065
Country [2] 303508 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303825 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 303825 0
Ethics committee country [1] 303825 0
Australia
Date submitted for ethics approval [1] 303825 0
29/07/2019
Approval date [1] 303825 0
09/09/2019
Ethics approval number [1] 303825 0

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

Contacts
Principal investigator
Name 94942 0
Dr Ingrid Hopper
Address 94942 0
Nucelus Network
Level 5,
Burnet Tower,
89 Commercial Road
Melbourne,
VIC 3004
Country 94942 0
Australia
Phone 94942 0
+61 03 8593 9800
Fax 94942 0
Email 94942 0
i.hopper@nucleusnetwork.com.au
Contact person for public queries
Name 94943 0
Ingrid Hopper
Address 94943 0
Nucelus Network
Level 5,
Burnet Tower,
89 Commercial Road
Melbourne,
VIC 3004
Country 94943 0
Australia
Phone 94943 0
+61 03 8593 9800
Fax 94943 0
Email 94943 0
i.hopper@nucleusnetwork.com.au
Contact person for scientific queries
Name 94944 0
Julia Zhu
Address 94944 0
Reistone Biopharma Co. Ltd.
298 Xiangke Road, 2/F, 201-204, Zhangjiang
High-tech Park, Pudong, Shanghai, China
Country 94944 0
China
Phone 94944 0
+862168813306
Fax 94944 0
Email 94944 0
Julia.zhu@reistonebio.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
This is TBC


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.