Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05491421




Registration number
NCT05491421
Ethics application status
Date submitted
1/08/2022
Date registered
8/08/2022
Date last updated
16/05/2023

Titles & IDs
Public title
A Study of ZT002 in Healthy Participants
Scientific title
A Phase 1, Randomized, Parallel Assignment, Double Blind, Placebo Controlled, Single and Multiple Ascending Dose, Safety, Tolerability, and Pharmacokinetic Study of ZT002 in Healthy Participants
Secondary ID [1] 0 0
ZT002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 Diabetes Mellitus 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ZT002
Other interventions - Placebo

Experimental: A (ZT002) - Drug: ZT002
Dose level:
SAD dose (Cohort 1-4)
0.03 mg/kg, 0.09 mg/kg, 0.18 mg/kg, 0.3 mg/kg;
MAD dose (Cohort 1-3)
Cohort 1: 7.0mg, 10mg, 20mg;
Cohort 2: 10 mg, 20mg, 40mg;
Cohort 3: To be decided post safety review meetings
Dose: Subcutaneous Injection

Placebo Comparator: B (Placebo) - Dose level:
SAD dose (Cohort 1-4)
0.03 mg/kg, 0.09 mg/kg, 0.18 mg/kg, 0.3 mg/kg;
MAD dose (Cohort 1-3)
Cohort 1: 7.0mg, 10mg, 20mg;
Cohort 2: 10 mg, 20mg, 40mg;
Cohort 3: To be decided post safety review meetings
Dose: Subcutaneous Injection


Treatment: Drugs: ZT002
Participants will receive a single subcutaneous (SC) ZT002 dose of 0.03, 0.09, 0.18, or 0.3 mg/kg respectively, for SAD Cohorts 1 to 4 under fasted conditions.
Participants will MAD Cohorts will receive a single subcutaneous (SC) ZT002 in following doses under fasting conditions-
Cohort 1: 7.0mg, 10mg, 20mg;
Cohort 2: 10 mg, 20mg, 40mg;
Cohort 3: To be decided post safety review meetings

Other interventions: Placebo
Participants will receive same volume as of the study drug of 0.03, 0.09, 0.18, or 0.3 mg/kg respectively, for SAD Cohorts 1 to 4 under the fasted condition.
Participants in MAD cohorts will receive same volume as study drug in the following cohorts under fasted condition-
Cohort 1: 7.0mg, 10mg, 20mg;
Cohort 2: 10 mg, 20mg, 40mg;
Cohort 3: To be decided post safety review meetings
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety and tolerability of a single escalation dose of ZT002 through the incidence and severity of treatment emergent adverse events in SAD Cohorts. Number of participants with treatment-emergent adverse events.
Timepoint [1] 0 0
Up to 71 days
Primary outcome [2] 0 0
Safety and tolerability of a single escalation dose of ZT002 through the incidence severity of serious adverse events in SAD Cohorts. Number of participants with serious adverse events.
Timepoint [2] 0 0
Up to 71 days
Primary outcome [3] 0 0
To assess safety and tolerability of multiple escalation doses of ZT002 in healthy participants with a BMI range of 26 kg/m2 to 40 kg/m2 and a body weight of =80 kg through number of participants with treatment emergent adverse events in MAD Cohorts.
Timepoint [3] 0 0
up to 85 days
Primary outcome [4] 0 0
To assess safety and tolerability of multiple escalation doses of ZT002 in healthy participants with a BMI range of 26 kg/m2 to 40 kg/m2 and a body weight of =80 kg through incidence severity of serious adverse events in MAD Cohorts.
Timepoint [4] 0 0
Upto 85 days
Secondary outcome [1] 0 0
The Pharmacokinetics (PK) profile of a single escalation dose of ZT002 in healthy participants in SAD and MAD Cohorts. Parameter: Maximum observed plasma concentration of ZT002 (Cmax)
Timepoint [1] 0 0
Up to 85 days
Secondary outcome [2] 0 0
The Pharmacokinetics (PK) profile of a single escalation dose of ZT002 in healthy participants in SAD and MAD Cohorts. Parameter: Area under the drug-time curve from 0 h after dosing to the last quantifiable concentration time point (AUC0-last)
Timepoint [2] 0 0
Up to 85 days
Secondary outcome [3] 0 0
The Pharmacokinetics (PK) profile of a single escalation dose of ZT002 in healthy participants in SAD and MAD cohorts. Parameter: Area under the drug-time curve to infinity (AUC0-inf)
Timepoint [3] 0 0
Up to 85 days
Secondary outcome [4] 0 0
The anti-drug antibody (ADA) response through an anti-drug antibody assay in SAD and MAD cohorts.
Timepoint [4] 0 0
Up to 85 days
Secondary outcome [5] 0 0
The anti-drug antibody (ADA) response through testing serum or plasma of the participant post dosing in SAD and MAD cohorts.
Timepoint [5] 0 0
Up to 85 days

Eligibility
Key inclusion criteria
1. Male or female, age 18-55 years, both inclusive, at time of informed consent

2. Body Mass Index (BMI) between 22.0~35.0 kg/m2 both included. For the MAD portion only,
participants with BMI range of 26 kg/m2 to 40 kg/m2 and a body weight of = 80 kg will
be included.

3. In good health, determined by no clinically significant findings from medical history,
physical examination, 12-lead ECG, vital signs measurements, and clinical laboratory
evaluations at screening and before administration of study drug, as assessed by the
Investigator

4. Able to comprehend and willing to sign an informed consent form (ICF) and to abide by
the study restrictions.

5. Has no relevant dietary restrictions (not including those common restrictions that can
be easily accommodated, i.e., veganism, vegetarianism, halal, etc.), and willing to
consume standard meals within the options provided by the site

6. Male participants must be surgically sterile (>30 days since vasectomy with no viable
sperm), abstinent, or if engaged in sexual relations with a woman of childbearing
potential (WOCBP), the participant must be surgically sterile (>30 days since
vasectomy with no viable sperm) or the participant and his partner must be using an
acceptable, highly effective contraceptive method from 4 weeks prior to dosing until
study completion, including the follow-up period.

Female participants that are WOCBP must be non-pregnant and non-lactating, and using
an acceptable, highly effective contraceptive method from 4 weeks prior to dosing
until study completion, including the follow-up period, OR must be abstinent from
heterosexual intercourse OR their partner must be surgically sterile (>30 days since
vasectomy with no viable sperm), provided the male partner is a sole partner.

Female participants that are not WOCBP must have documented evidence of surgical
sterilization at least 6 months prior to Screening (e.g., hysterectomy, bilateral
salpingectomy, or bilateral oophorectomy), OR must be postmenopausal for =12 months.
Postmenopausal status will be confirmed through testing of follicle-stimulating
hormone (FSH) levels = 40 IU/L at Screening for amenorrhoeic female participants.

Acceptable methods of contraception include the use of condoms AND the use of an
effective contraceptive for the female partner that includes: oral contraceptive pill
(OCPs), long acting implantable hormones, injectable hormones, contraceptive patches,
a vaginal ring or an intrauterine device (IUD).

Participants with same-sex partners (abstinence from penile-vaginal intercourse) are
eligible when this is their preferred and usual lifestyle, and no contraception is
required.

7. Male participants agree not to donate sperm for at least 90 days after the last dose
of study drug.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. History of significant drug allergy or drug hypersensitivity.

2. Known or suspected allergy to trial product or related products.

3. Significant history or clinical manifestation of any metabolic, allergic,
dermatological, hepatic, renal, hematological, pulmonary, cardiovascular,
gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as
determined by the Investigator (or designee), that could adversely affect the safety
of the participant or their likelihood to comply with the protocol or complete the
study per protocol. Fully resolved childhood asthma is not exclusionary. Gestational
diabetes is exclusionary.

4. eGFR value =90 mL/min/1.73m2 using the MDRD equation.

5. Clinically significant abnormal laboratory test results during the Screening and
before administration of study drug, as judged by the Investigator.

6. Family or personal history of multiple endocrine neoplasia type 2 (MEN2) or medullary
thyroid carcinoma (MTC) as declared by the participant.

7. History of malignancy, except for non-melanoma skin cancer, excised more than 2 years
ago and cervical intraepithelial neoplasia that has been successfully cured more than
5 years prior to Screening.

8. History of acute or chronic pancreatitis.

9. Calcitonin equal or above 50 ng/L at screening.

10. Fever (body temperature >37.5°C) or symptomatic viral or bacterial infection within 2
weeks prior to Screening and Day -1.

11. History of severe allergic or anaphylactic reactions.

12. QTcF > 450 ms for male participants or > 470 ms for female participants, or any other
abnormal ECG findings that are considered by the Investigator to be clinically
significant, at Screening and before administration of study drug.

13. History or presence of a condition associated with significant immunosuppression.

14. History of life -threatening infection (e.g. meningitis).

15. Infections requiring parenteral antibiotics within the 6 months prior to Screening.

16. History of drug/chemical substance abuse within 1 year from Screening.

17. Positive alcohol breath test result, or positive urine drug screen (confirmed by
repeat), at Screening or check-in.

18. Regular alcohol consumption (by self-declaration) in the past 6 months, defined as
greater than 21 alcohol units per week for males and 14 units per week for females
(where 1 unit = 284 mL of beer, 25 mL of 40% spirit or a 125 mL glass of wine).

Unwilling to abstain from alcohol consumption from 24 hours prior to admission to the
CRU, during the residency period, and 24 hours prior to each non-residential visit.

19. Have smoked >5 cigarettes or use the equivalent tobacco or nicotine containing
products per day in the past 1 month prior to Screening (vaping with nicotine
containing vapes included) or unable or unwilling to refrain from smoking and use of
nicotine substitute products until after the final study visit, as judged by the
Investigator.

20. Positive test for hepatitis C antibody (HCV), hepatitis B surface antigen (HBsAg), or
human immunodeficiency virus (HIV) antibody at Screening.

21. Previously dosed in a clinical trial involving this or other IPs within the last 3
months before dosing.

22. Blood donation or considerable blood loss - more than 400 mL, during the 3 months
prior to study start, and plasma donation within 7 days prior to study start.

23. Systolic blood pressure >140 or <90 mmHg, diastolic blood pressure >90 or <40 mmHg,
and pulse rate >100 or <40 beats per minute. Abnormal values should be confirmed by a
repeat measurement (one repeat only).

24. Impaired hepatic function measured as ALT (Alanine aminotransferase), AST (Aspartate
aminotransferase), alkaline phosphatase above 1.5 times the upper reference limit (one
retest of the initial test is permitted, the last result being conclusive).

25. Confirmed diagnosis of diabetes mellitus type 1, type 2, or of any other forms at any
time, and/or occurrence of documented or suspected hypoglycemic episodes within 12
months prior to Screening, and any current or prior use of insulin secretagogues
(e.g., sulfonylurea) or insulin.

26. Impaired glucose tolerance results for oral glucose tolerance test (OGTT) performed at
screening. A blood glucose level =7.8 mmol/L at 2 hours will be considered as impaired
glucose tolerance.

27. Those who have been vaccinated within 4 weeks prior to screening or who are scheduled
to be vaccinated within 4 weeks of dosing, except for COVID-19 and influenza vaccines,
exclusionary when the participant is scheduled to be vaccinated within 1 week of
dosing.

28. Exposure to any significantly immune suppressing drug (including experimental
therapies as part of a clinical trial) within the 4 months prior to Screening or 5
half-lives, whichever is longer.

29. Use of prescription or non-prescription systemic or topical medicinal products (except
routine vitamins, supplements, acetylsalicylic acid, paracetamol and contraceptives;
herbal preparations or dietary supplements that are specifically marketed for control
of body weight or appetite remain excluded) within 3 weeks (or within 5 half-lives of
the medicinal product, whichever is longest) prior to the dosing and for the duration
of the study. Paracetamol/acetaminophen (1-2 therapeutic doses per week) may be used
for minor ailments during the course of the study, at the discretion of the
Investigator.

30. Poor peripheral venous access.

31. Participant is unwilling to refrain from strenuous exercise (including weightlifting)
from 48 hours prior to admission to the investigational site until completion of the
residency (inpatient) period, and from 48 hours prior to the Day 15, Day 29, Day 43,
and Day 71/Early Withdrawal visits.

32. Any disorder or other circumstance which in the Investigator's opinion might
jeopardize participant's safety, evaluation of results, or compliance with the
protocol, meaning that, in the opinion of the Investigator (or designee), the
participant should not participate in this study.

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
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
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
2/09/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
14/04/2024
Actual
Sample size
Target
56
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Q-Pharm Pty Limited - Herston
Recruitment postcode(s) [1] 0 0
- Herston

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
QL Biopharmaceutical Australia 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
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
Beijing QL Biopharmaceutical Co.,Ltd
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This study will comprise a randomized, parallel assignment, double blind, placebo controlled,
single and multiple ascending dose, safety, tolerability and pharmacokinetic study of ZT002
in healthy participants.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05491421
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Kristi McLendon
Address 0 0
Nucleus Network Pty Ltd.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Yuanyuan Zhang
Address 0 0
Country 0 0
Phone 0 0
+86 13581521105
Fax 0 0
Email 0 0
yuanyuan@qlbiopharm.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05491421