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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04389775




Registration number
NCT04389775
Ethics application status
Date submitted
24/03/2020
Date registered
15/05/2020
Date last updated
15/05/2020

Titles & IDs
Public title
To Evaluate the Safety, Tolerability, PK, and PD of XW003 Injection in Healthy Adult Participants
Scientific title
A Phase 1, Randomized, Double-blind, Placebo-controlled, SAD Study to Evaluate the Safety, Tolerability, PK, and PD of XW003 (an Investigational Recombinant Human GLP-1 Analogue) Injection in Healthy Adult Participants
Secondary ID [1] 0 0
SCW0502-1011/1012
Universal Trial Number (UTN)
Trial acronym
XW003
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 Diabetes Mellitus 0 0
NASH - Nonalcoholic Steatohepatitis 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Diet and Nutrition 0 0 0 0
Obesity
Metabolic and Endocrine 0 0 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - XW003
Treatment: Drugs - Volume-matching Placebo

Active Comparator: Drug - Subcutaneously administer a single dose of XW003, ranging from 0.03mg to 2.0mg, every cohort by the body weight.

Placebo Comparator: placebo - Subcutaneously administer a single dose of volume-matching placebo, ranging from 0.03mg to 2.0mg, every cohort by the body weight.


Treatment: Drugs: XW003
Participants in each cohort will be randomised to receive a SC dose of XW003 on Day 1 after overnight fasting by body weight range:
Proposed XW003 Dose Levels (50 kg-75 kg): 0.03mg, 0.1mg, 0.2mg, 0.4mg, 0.8mg, 1.2mg and 1.6mg respectively for Cohorts A1 TO A7.
Proposed XW003 Dose Levels (76 kg-90 kg): 0.03mg, 0.1mg, 0.25mg, 0.5mg, 1.0 mg, 1.6mg, 2.0mg These doses are subject to change following SRC review of each cohort - XW003 dose level will not exceed 2.0 mg.

Treatment: Drugs: Volume-matching Placebo
Participants in each cohort will be randomised to receive a SC dose of volume-matching placebo on Day 1 after overnight fasting by body weight range:
Proposed Placebo Dose Levels (50 kg-75 kg): 0.03mg, 0.1mg, 0.2mg, 0.4mg, 0.8mg, 1.2mg and 1.6mg respectively for Cohorts A1 to A7.
Proposed Placebo Dose Levels (76 kg-90 kg): 0.03mg, 0.1mg, 0.25mg, 0.5mg, 1.0 mg, 1.6mg, 2.0mg These doses are subject to change following SRC review of each cohort - dose level will not exceed 2.0 mg.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of treatment emergent adverse events (TEAEs) - Count of adverse events
Timepoint [1] 0 0
From administration of XW003 on Day 1 to the last follow-up visit
Secondary outcome [1] 0 0
Maximum observed XW003 plasma concentration - Calculated based on XW003 measured in blood.
Timepoint [1] 0 0
22 days
Secondary outcome [2] 0 0
Time of the maximum observed XW003 plasma concentration - Calculated based on XW003 measured in blood.
Timepoint [2] 0 0
22 days
Secondary outcome [3] 0 0
Area under the XW003 plasma concentration-time curve - Calculated based on XW003 measured in blood.
Timepoint [3] 0 0
22 days
Secondary outcome [4] 0 0
Apparent terminal half-life of XW003 - Calculated based on XW003 measured in blood.
Timepoint [4] 0 0
22 days
Secondary outcome [5] 0 0
Apparent terminal elimination rate constant of XW003 - Calculated based on XW003 measured in blood.
Timepoint [5] 0 0
22 days
Secondary outcome [6] 0 0
Apparent total clearance of XW003 - Calculated based on XW003 measured in blood.
Timepoint [6] 0 0
22 days
Secondary outcome [7] 0 0
Apparent volume of distribution of XW003 - Calculated based on XW003 measured in blood.
Timepoint [7] 0 0
22 days
Secondary outcome [8] 0 0
Change from Baseline in body weight - Percentage of body weight loss
Timepoint [8] 0 0
22 days
Secondary outcome [9] 0 0
Change from Baseline in fasting plasma glucose - Percentage of fasting plasma glucose change
Timepoint [9] 0 0
22 days
Secondary outcome [10] 0 0
Change from Baseline in plasma insulin and pro-insulin - Percentage of plasma insulin and pro-insulin change
Timepoint [10] 0 0
22 days
Secondary outcome [11] 0 0
Change from Baseline in plasma C-peptide - Percentage of plasma C-peptide change
Timepoint [11] 0 0
22 days
Secondary outcome [12] 0 0
Change from Baseline in plasma glucagon - Percentage of plasma glucagon change
Timepoint [12] 0 0
22 days
Secondary outcome [13] 0 0
Change from Baseline in plasma lipids (triglyceride, low-density lipoprotein [LDL], and high-density lipoprotein [HDL]) - Percentage of plasma lipids (triglyceride, low-density lipoprotein [LDL], and high-density lipoprotein [HDL]) change
Timepoint [13] 0 0
22 days
Secondary outcome [14] 0 0
Incidence of anti-XW003 antibodies at end of study - Count of episodes
Timepoint [14] 0 0
Pre-dose of XW003 on Day 1, end of study visit on Day 22

Eligibility
Key inclusion criteria
1. Healthy male or female participants, aged 18 to 55 years (inclusive at the time of
informed consent);

2. Participants must be in good general health, with no significant medical history, have
no clinically significant abnormalities on physical examination at Screening and/or
before administration of study drug;

3. Participants must have a BMI greater than or equal to 20.0 kg/m2 and less than or
equal to 35.0 kg/m2 and weigh greater than or equal to 50 kg but less than or equal to
90 kg at Screening;

4. Stable body weight for at least three (3) months prior to Screening (i.e., <5%
change);

5. Participants must have A1c below 6.4%, FPG: 3.9 ~ 6.1 mmol/L (both inclusive) or
70~110 mg/dL (both inclusive). All other clinical laboratory values must be within
normal range as specified by the testing laboratory, unless deemed not clinically
significant by the Investigator or delegate;

6. Non-smoker and/or casual smoker who uses no more than 10 cigarettes (or equivalent
quantity of any other nicotine containing products e.g., cigars, chewing tobacco,
snuff, etc.) per week. Participants must abstain from smoking 5 days prior to
admission and throughout the confinement period, and test negative on Day -1 for urine
cotinine test. Participants must also abstain from smoking 72 hours prior to each
outpatient visit;

7. Participants must agree to abstain from alcohol intake from 48 hours prior to
admission and during the confinement period;

8. Women of childbearing potential (WOCBP) must be non-pregnant and must use an
acceptable, highly effective double contraception from Screening until study
completion, including the follow up period.

9. Males must not donate sperm for at least 90 days after the last dose of study drug;

10. Participants must have the ability and willingness to attend the necessary visits to
the CRU;

11. Participants must be willing and able to provide written informed consent after the
nature of the study has been explained and prior to the commencement of any study
procedures.
Minimum age
18 Years
Maximum age
55 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Prior or ongoing medical conditions, medical history, physical findings, or laboratory
abnormality that, in the Investigator's (or delegate's) opinion, may require treatment
or render the participant unlikely to fully complete the study, or any condition that
presents undue risk from the IP or procedures or interfere with study assessments;

2. Confirmed diagnosis of diabetes mellitus type 1, type 2, or of any other forms at any
time, and/or occurrence of documented or suspected hypoglycaemic episodes within 12
months prior to Screening;

3. Personal or family history of medullary thyroid carcinoma or multiple endocrine
neoplasia type 2;

4. History of acute or chronic pancreatitis;

5. Participants must be willing not to undertake any strenuous exercise, including but
not limited to weightlifting (greater than 5 times per week) within 5 days prior to
first study drug administration and for the duration of the study (including the
follow-up period);

6. Participants must not start or having started participation in any medical (e.g.,
assisted by a clinical dietician or nutritionist) or non-medical (e.g., by a gym
coach) diet and/or exercise programme within 3 months prior to Screening and for the
duration of the study (including the follow-up period);

7. Use and/or planned use of any approved or unapproved weight-lowering medication(s)
(including but not limited to orlistat, sibutramine, rimonabant, phentermine, or
liraglutide) and/or medical device(s) within 3 months prior to Screening and for the
duration of the study (including the follow-up period);

8. Previous history of any major gastrointestinal (including hepatobiliary and/or
pancreatic) surgeries, including but not limited to sleeve, subtotal, or total
gastrectomy, gastrojejunostomy, gastroduodenectomy, gastroduodenostomy, jejunectomy,
ileectomy (proto)colectomy, hepatectomy, and pancreatectomy (except for appendectomy
or cholecystectomy) and planned performance of one or more of the above mentioned for
the duration of the study (including the follow-up period);

9. History of cerebral stroke (including but not limited to cerebral
infarction/haemorrhage) within 12 months prior to Screening;

10. History of acute coronary syndrome (angina pectoris/myocardial infarction) and any
other major cardiac conditions (including but not limited to myocarditis, cardiac
insufficiency/failure, and any clinically significant arrythmia[s]) within 12 months
prior to Screening;

11. Systolic blood pressure (BP) greater than 140 mmHg and/or less than 90 mmHg and/or
diastolic BP greater than 90 mmHg and/or less than 40 mmHg and/or pulse rate greater
100 bpm and/or less than 40 bpm at Screening with one repeat allowed per by the
Investigator or delegate at Screening and/or on Admission

12. Any clinically significant arrhythmia(s) at Screening ECG; specifically, the
participant's corrected QT interval (QTcF) (Fridericia's correction) is greater than
450 ms at Screening and on Day -1. An out-of-range or abnormal ECG may be repeated
during Screening. On admission, three ECGs should be recorded consecutively, and the
Investigator must evaluate the triplicate ECG. If the participant's QTcF is greater
than 450 ms on at least two ECGs, the participant must be excluded;

13. Any medically uncontrolled respiratory disease(s) and/or condition(s), including but
not limited to severe current asthma, chronic obstructive pulmonary disease, and
obstructive sleep apnoea syndrome;

14. Fever (body temperature greater than 38°C) or symptomatic viral or bacterial infection
within 2 weeks prior to Screening;

15. Clinically significant gastrointestinal disease(s), including but not limited to
inflammatory bowel disease, irritable bowel syndrome, celiac disease, dyspepsia,
apparent diabetic gastroparesis, and diabetic diarrhoea;

16. With alanine aminotransferase (ALT), aspartate aminotransferase (AST), and/or alkaline
phosphatase (ALP) greater than 1.5 × upper limit of normal (ULN) at Screening. Repeat
testing at Screening is acceptable for out of range values following approval by the
Investigator or delegate;

17. With a confirmed creatinine clearance (CLcr) using the Cockcroft-Gault equation below
90 mL/min. Repeat testing at Screening is acceptable for out of range values following
approval by the Investigator or delegate;

18. History of clinically significant endocrine condition(s), including but not limited to
hyper/hypothyroidism and/or hyper/hypoadrenalism;

19. History of primary or recurrent malignancy, except for non-melanoma skin cancer
excised more than 2 years prior to Screening and/or cervical intraepithelial neoplasia
having been successfully cured more than 5 years prior to Screening;

20. With clinically significant haematologic abnormalities, including but not limited to
haemoglobin above 180 g/L and/or below 110 g/L, white blood cell count (WBC) above
10.5×10^9/L and/or below 3.5×10^9/L, absolute neutrophil count above 7.0×10^9/L and/or
below 2.0×10^9/L, and/or platelet count above 300×10^9/L and/or below 130×10^9/L.
Repeat testing at Screening is acceptable for out of range values following approval
by the Investigator or delegate;

21. With any other clinically significant laboratory abnormalities in clinical
biochemistry, coagulation function, and/or urinalysis. Repeat testing at Screening is
acceptable for out of range values following approval by the Investigator or delegate;

22. With positive test result(s) for hepatitis C virus (HCV) antibody, hepatitis B surface
antigen (HBsAg), or human immunodeficiency virus (HIV) antibody at Screening;

23. History of life-threatening infection (e.g. meningitis) and/or any major infections
requiring parental antimicrobials within 6 months prior to Screening;

24. Regular alcohol consumption (by self-declaration) defined as greater than 21 alcohol
units per week (where 1 unit = 284-mL of beer, 25-mL of 40% spirit or a 125-mL glass
of wine). Participant is unwilling to abstain from alcohol beginning 48 hours prior to
admission to the CRU and during the confinement period;

25. With a history of substance abuse or dependency in the last 12 months, or a history of
recreational intravenous drug use over the last 5 years (by self-declaration);with a
positive toxicology screening panel (urine test including qualitative identification
of barbiturates, tetrahydrocannabinol [THC], amphetamines, methamphetamines,
methylenedioxy-methamphetamine [MDMA], phencyclidine, benzodiazepines, opiates and
cocaine), or alcohol breath test;

26. History of severe allergic or anaphylactic reactions;

27. Known or suspected intolerance or hypersensitivity to the IP, close related compounds,
or any of the stated ingredients;

28. Blood donation or significant blood loss (greater than or equal to 400 mL) within 60
days prior to the first study drug administration;

29. Plasma donation within 7 days prior to the first study drug administration;

30. Being pregnant or lactating at Screening or planning to become pregnant (self or
partner) at any time during the study and for at least 3 months after the last dose of
study drug;

31. Use of any IP or investigational medical device within 30 days prior to Screening, or
5 half lives of the product (whichever is the longest) or participation in more than
four investigational drug studies within 1 year prior to Screening;

32. Previous treatment with glucagon-like peptide 1 (GLP-1) agonists within the last 3
months;

33. Use of any prescription drug(s) and medical device(s) (other than hormonal
contraception:

OCPs, long-acting implantable hormones, injectable hormones, a vaginal ring, or an
IUD) within 2 weeks prior to the first study drug dosing or use of any over
the-counter (OTC) medication, herbal remedies, supplements or vitamins within 1 week
prior to the first study drug dosing and during the course of the study without prior
approval of the Investigator and MM. Use of simple analgesic(s) (e.g., paracetamol, a
nonsteroidal anti-inflammatory drug [NSAID]) may be permitted at the discretion of the
Investigator;

34. Present comedication with drugs known to interfere with glucose metabolism, such as
systemic corticosteroids, non-selective beta-blockers, and monoamine oxidase
inhibitors;

35. Presence of any underlying physical and/or psychological medical condition that, in
the opinion of the Investigator, would make it unlikely that the subject will comply
with the protocol or complete the study per protocol.

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 analysing the results/data
Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 0 0
3004 - Melbourne

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Sciwind Biosciences APAC CO Pty. Ltd.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Novotech (Australia) Pty Limited
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
XW003 is an acylated human GLP-1 analogue and is being development for obesity management.

This is a first-in-human (FIH), single-centre, double blind, randomised, SAD study of XW003
conducted in healthy adult participants. The study is designed to evaluate the safety,
tolerability, PK, and PD of XW003 in healthy participants.
Trial website
https://clinicaltrials.gov/show/NCT04389775
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
HONG QIN
Address 0 0
Country 0 0
Phone 0 0
(+86)13679290113
Fax 0 0
Email 0 0
qinhong@sciwind.com.cn
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04389775