A Randomized, Double-blind, Placebo-controlled, Multicenter, Multiple Ascending Dose Phase Ib Study in Subjects With Type 2 Diabetes to Evaluate the Safety, Tolerability and Pharmacokinetic Profile of TG103 Injection

CSPC ZhongQi Pharmaceutical Technology Co., Ltd.0 sites54 target enrollmentApril 2021

ConditionsType 2 Diabetes

InterventionsTG103 Placebo

DrugsTG103 Placebo

Overview

Phase: Phase 1
Intervention: TG103
Conditions: Type 2 Diabetes
Sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
Enrollment: 54
Primary Endpoint: Safety and tolerability assessed by incidence and severity of adverse events
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

Brief Summary

The main purpose of this study is to assess the safety and tolerability of multiple ascending doses of TG103 in subjects with type 2 diabetes.

Detailed Description

This study is a randomized, double-blind, placebo-controlled, multicenter, dose-escalating study to characterize the safety (including the anti-drug antibodies(ADA)), tolerability pharmacokinetics (PK) and pharmacodynamic parameters（PD）of TG103. The study will consist of 3 periods: an approximately 2-week lead-in period, followed by a 12-week treatment period, and a 3-week safety follow-up period. Three dose groups (7.5mg, 15mg and 22.5mg) of subjects will be enrolled and dosed sequentially; 12

Registry

clinicaltrials.gov

Start Date

April 2021

End Date

March 2022

Last Updated

5 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

CSPC ZhongQi Pharmaceutical Technology Co., Ltd.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Subjects who fully understand the test content and possible adverse reactions and voluntarily participate in the trial and sign the informed consent form;
•2.Age: 18 to 75 years of age inclusive; no gender limitation;
•Weight：body mass index (BMI) within the range of 18.5-35 kg/m2 (inclusive), BMI = weight (kg) / height 2 (m2);
•Patients have diagnosed with type 2 diabetes ≤ 3 years according to the World Health Organization (WHO1999) classification; and not on medication or without a history of regular medication for more than 1 week in the 3 months prior to screening (subjects with a history of medication only include those with a history of oral medication and a history of short-term intensive insulin therapy (≤ 2 weeks));
•7.0% ≤ HbA1c ≤ 10.0%;
•Subjects of childbearing potential must use reliable methods of contraception from the date of signing an informed consent to at least 3 months after the last dose;
•The subject has the ability to communicate properly with the researcher and willing to fully comply with the research protocol.

Exclusion Criteria

•Fasting plasma glucose ≥13.9mmol/L or a history of severe hypoglycemia (blood sugar below 2.2mmol/L);
•Systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg during screening;
•During the screening period, the white blood cell count fall outside the reference range by 10%, or hemoglobin\<100g / L;
•Have one or more positive tests in Hepatitis B surface antigen, hepatitis C virus antibody, anti-human immunodeficiency virus antibody or anti- Treponema pallidum-specific antibody;
•Aspartate aminotransferase(AST) or Alanine aminotransferase (ALT) \> 2.5x upper limit of normal (ULN), or triglyceride \> 5.7mmol/L or eGFR\<60 mL/（min\*1.73 m2）during the screening period;
•Hypercortisolism, polycystic ovary syndrome, abnormal thyroid function (those who need to be given medication or who have not reached clinical stability after treatment and whose medication still needs to be adjusted), etc. or other diseases that may affect blood glucose metabolism.
•Have a personal or family history of medullary thyroid carcinoma (MTC) or type 2 multiple endocrine neoplasia, or other genetic diseases that are susceptible to medullary cancer; personal or family history of medullary thyroid carcinoma (MTC) or type 2 multiple endocrine neoplasia, or other genetic diseases that are susceptible to medullary cancer;
•Acute complications of diabetes (including diabetic ketoacidosis, hyperosmolar nonketotic diabetic coma, lactic acidosis and hypoglycemia coma);
•Proliferative diabetic retinopathy, foot ulcers/gangrene, and manifestations of peripheral neuropathy with obvious symptoms (e.g., gastroparesis, urinary retention, intestinal obstruction, urinary incontinence, and painful peripheral neuropathy);
•Lost more than 400 ml of blood due to blood donation or other reasons within 3 months before the screening period;

Arms & Interventions

TG103

TG103 will be administered via subcutaneous injection once weekly in subjects with type 2 diabetes.

Intervention: TG103

Placebo

Placebo will be administered via subcutaneous injection once weekly in subjects with type 2 diabetes.

Intervention: Placebo

Outcomes

Primary Outcomes

Safety and tolerability assessed by incidence and severity of adverse events

Time Frame: up to 15 weeks

A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module

Secondary Outcomes

Area under the plasma concentration versus time curve (AUC)(Day1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78)
glycosylated hemoglobin (HbA1c)(Day15, 29, 43, 57,71, and 78,)
The occurrence of TG103 anti-drug antibodies (ADA)(up to 15 weeks)
Peak Plasma Concentration (Cmax),(Day1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78)
Time to maximum plasma concentration (Tmax)(Day1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78)
Half time (t1/2),(Day1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78)
Apparent clearance (CL/F)(Day1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78)