To Evaluate the Safety, Tolerability, PK, and PD of XW003 Injection in Healthy Adult Participants

NCT04389775 | Completed Phase 1 DMC

• 2 other identifiers: SCW0502-1011/1012ACTRN12620000344998
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

XW003 is an acylated human GLP-1 analogue and is being development for diabetes mellitus, obesity and nonalcoholic steatohepatitis (NASH) management. This is a first-in-human (FIH), single-centre, double blind, randomised, SAD and MAD study of XW003 conducted in healthy adult participants. The study is designed to evaluate the safety, tolerability, PK, and PD of XW003 in healthy adult participants.

Conditions

Type 2 Diabetes Mellitus; Obesity; Nonalcoholic Steatohepatitis

Keywords

Type 2 Diabetes Mellitus; Obesity; Nonalcoholic Steatohepatitis

Outcome Measures

Primary Outcomes (1)

• Number of treatment emergent adverse events (TEAEs)

  Count of adverse events

  From administration of XW003 on Day 1 to the last follow-up visit

Secondary Outcomes (24)

• Maximum observed XW003 plasma concentration

  36 days

• Time of the maximum observed XW003 plasma concentration

  36 days

• Area under the XW003 plasma concentration-time curve

  36 days

• Apparent terminal half-life of XW003

  36 days

• Apparent terminal elimination rate constant of XW003

  36 days

Study Arms (4)

Cohort A

EXPERIMENTAL

Subcutaneously administer a single dose of XW003, ranging from 0.03mg to 1.0mg, every cohort by the body weight.

Drug: Cohort A

Placebo A

PLACEBO COMPARATOR

Subcutaneously administer a single dose of volume-matching placebo, ranging from 0.03mg to 1.0mg, every cohort by the body weight.

Drug: Placebo A

Cohort B

EXPERIMENTAL

Subcutaneously administer multiple SC doses of XW003, ranging from 0.2mg to 0.6mg, once weekly for 6 weeks.

Drug: Cohort B

Placebo B

PLACEBO COMPARATOR

Subcutaneously administer multiple SC doses of volume-matching placebo, ranging from 0.2mg to 0.6mg, once weekly for 6 weeks.

Drug: Placebo B

Interventions

Cohort A DRUG

Participants in each cohort (A1 to A6) will be randomised to receive a SC dose of XW003 on Day 1 after overnight fasting by body weight range: 1. Proposed XW003 Dose Levels (50 kg-75 kg): 0.03mg, 0.1mg, 0.2mg, 0.4mg, 0.8mg and 0.6mg respectively for Cohorts A1 to A6. 2. Proposed XW003 Dose Levels (76 kg-90 kg): 0.03mg, 0.1mg, 0.25mg, 0.5mg, 1.0 mg and 0.6mg. These doses are subject to change following SRC review of each cohort - XW003 dose level will not exceed 2.0 mg.

Also known as: GLP-1 analogue

Cohort A

Placebo A DRUG

Participants in each cohort (A1 to A6) will be randomised to receive a SC dose of volume-matching placebo on Day 1 after overnight fasting by body weight range: 1. Proposed Placebo Dose Levels (50 kg-75 kg): 0.03mg, 0.1mg, 0.2mg, 0.4mg, 0.8mg, and 0.6mg respectively for Cohorts A1 to A6. 2. Proposed Placebo Dose Levels (76 kg-90 kg): 0.03mg, 0.1mg, 0.25mg, 0.5mg, 1.0 mg and 0.6mg. These doses are subject to change following SRC review of each cohort - dose level will not exceed 2.0 mg.

Also known as: Placebo

Placebo A

Cohort B DRUG

Participants in cohorts B1 to B3 (n=10 per cohort) will receive multiple SC doses of XW003 (n=8) once weekly for 6 weeks following an overnight fast of at least 10 hours. 1. Subject to change following SRC review of each cohort. 2. Following 4 weeks of once weekly dosing, the SRC will review the safety data (and PK data for Cohort B1 only) to determine the treatment for the following cohort and whether dosing can commence in parallel. 3. At least 3 days prior to Cohort B3 Week 3 (i.e., 3 days prior to the third dose in Cohort B3), the SRC will review the safety and PK data for Cohorts B1 and B2 to determine whether Cohort 3 dosing for Weeks 3 to 6 may commence.

Also known as: GLP-1 analogue

Cohort B

Placebo B DRUG

Participants in cohorts B1 to B3 (n=10 per cohort) will receive multiple SC doses of matching placebo (n=2) once weekly for 6 weeks following an overnight fast of at least 10 hours. 1. Subject to change following SRC review of each cohort. 2. Following 4 weeks of once weekly dosing, the SRC will review the safety data (and PK data for Cohort B1 only) to determine the treatment for the following cohort and whether dosing can commence in parallel. 3. At least 3 days prior to Cohort B3 Week 3 (i.e., 3 days prior to the third dose in Cohort B3), the SRC will review the safety and PK data for Cohorts B1 and B2 to determine whether Cohort 3 dosing for Weeks 3 to 6 may commence.

Also known as: Placebo

Placebo B

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male or female participants, aged 18 to 55 years (inclusive at the time of informed consent);
• 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;
• 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;
• Stable body weight for at least three (3) months prior to Screening (i.e., \<5% change);
• 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;
• 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;
• Participants must agree to abstain from alcohol intake from 48 hours prior to admission and during the confinement period;
• 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.
• Males must not donate sperm for at least 90 days after the last dose of study drug;
• Participants must have the ability and willingness to attend the necessary visits to the CRU;
• 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.

You may not qualify if:

• 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;
• 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;
• Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2;
• History of acute or chronic pancreatitis;
• 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);
• 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);
• 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);
• 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);
• History of cerebral stroke (including but not limited to cerebral infarction/hemorrhage) within 12 months prior to Screening;
• 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;
• 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
• 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;
• 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;
• Fever (body temperature greater than 38°C) or symptomatic viral or bacterial infection within 2 weeks prior to Screening;
• 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;

Sponsors & Collaborators

• Sciwind Biosciences APAC CO Pty. Ltd.: lead
• Hangzhou Sciwind Biosciences Co., Ltd.: collaborator

Study Sites (1)

Nucleus Network Pty Ltd

Melbourne, Victoria, 3004, Australia

Location

Related Publications (1)

• Guo W, Xu Z, Zou H, Li F, Li Y, Feng J, Zhu Z, Zheng Q, Zhu R, Wang B, Li Y, Hao S, Qin H, Jones CL, Adegbite E, Telusca L, Fenaux M, Zhong W, Junaidi MK, Xu S, Pan H. Discovery of ecnoglutide - A novel, long-acting, cAMP-biased glucagon-like peptide-1 (GLP-1) analog. Mol Metab. 2023 Sep;75:101762. doi: 10.1016/j.molmet.2023.101762. Epub 2023 Jun 24.

  PMID: 37364710 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Obesity; Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Fatty Liver; Liver Diseases; Digestive System Diseases

Study Officials

• Benjamin Snyder

  Nucleus Network

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: One of up to six (6) sequential cohorts (Cohorts A1 to A6). Participants in each cohort will be randomised to receive a single subcutaneous (SC) dose of either XW003 or matching placebo on Day 1 following an overnight fast. Two sentinel participants will receive a single SC dose of XW003 initially. If dosing of these sentinel participants proceeds without clinically significant safety signals in the first 48 hours post-dose, the remaining participants will receive a single dose of XW003 or placebo according to the randomisation schedule. Participants in Cohorts B1 to B3 (n=10 per cohort) will be randomized to receive a single SC dose of either XW003 (n=8) or matching placebo (n=2) once weekly for 6 weeks. Doses will be administered following an overnight fast of at least 10 hours.

Study Record Dates

• First Submitted: March 24, 2020
• First Posted: May 15, 2020
• Study Start: March 29, 2020
• Primary Completion: September 29, 2021
• Study Completion: September 29, 2021
• Last Updated: October 28, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)