NCT05943886

Brief Summary

This is a single-center, randomized, double-blind, placebo-controlled, escalating single-dose and multiple-dose study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of HEC88473 injection in healthy subjects, obese subjects and subjects with type 2 diabetes mellitus (T2DM).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
164

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Aug 2021

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 11, 2021

Completed
1.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 17, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 17, 2023

Completed
5 months until next milestone

First Submitted

Initial submission to the registry

July 5, 2023

Completed
8 days until next milestone

First Posted

Study publicly available on registry

July 13, 2023

Completed
Last Updated

July 17, 2023

Status Verified

July 1, 2023

Enrollment Period

1.5 years

First QC Date

July 5, 2023

Last Update Submit

July 14, 2023

Conditions

Healthy SubjectsObesityT2DM (Type 2 Diabetes Mellitus)

Outcome Measures

Primary Outcomes (4)

  • Frequency and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) after a single dose of HEC88473

    Adverse Events (AEs)

    Baseline to day 15

  • Frequency and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) after multiple dose of HEC88473

    Adverse Events (AEs)

    Baseline to day 43

  • Cmax

    Maximum observed serum concentration of HEC88473

    Predose and postdose 4、8、10、12、14、24、48、72、96、168、216、336 hours

  • AUC

    Area under the serum concentration-time curve (AUC)

    Predose and postdose 4、8、10、12、14、24、48、72、96、168、216、336 hours

Secondary Outcomes (5)

  • OGTT

    Day-1, Day3 and Day 7

  • Change from baseline of Adiponectin at day 38

    Baseline to day 38

  • Fasting lipid concentration

    Baseline to day 43

  • Change from baseline of HbA1c at day 38

    Baseline to day 38

  • Assessment of the incidence of anti drug antibodies (ADA) developed against HEC88473 after dosing

    Baseline to day 43

Study Arms (15)

Single dose of 0.5 mg HEC88473

EXPERIMENTAL

Healthy subjects, receiving a single dose of 0.5 mg HEC88473 (N=8) or placebo(N=2) after meal.

Drug: HEC88473 injectionDrug: Placebo

Single dose of 1.7 mg HEC88473

EXPERIMENTAL

Healthy subjects, receiving a single dose of 1.7 mg HEC88473 (N=8) or placebo(N=2) after meal.

Drug: HEC88473 injectionDrug: Placebo

Single dose of 5.1 mg HEC88473

EXPERIMENTAL

Healthy subjects, receiving a single dose of 5.1 mg HEC88473 (N=8) or placebo(N=2) after meal. Obese subjects, receiving a single dose of 5.1 mg HEC88473 (N=8) or placebo(N=2) after meal.

Drug: HEC88473 injectionDrug: Placebo

Single dose of 10.2 mg HEC88473

EXPERIMENTAL

Healthy subjects, receiving a single dose of 10.2 mg HEC88473 (N=8) or placebo(N=2) after meal.

Drug: HEC88473 injectionDrug: Placebo

Single dose of 17.0 mg HEC88473

EXPERIMENTAL

Healthy subjects, receiving a single dose of 17.0 mg HEC88473 (N=8) or placebo(N=2) after meal.

Drug: HEC88473 injectionDrug: Placebo

Single dose of 25.5 mg HEC88473

EXPERIMENTAL

Healthy subjects, receiving a single dose of 25.5 mg HEC88473 (N=8) or placebo(N=2) after meal.

Drug: HEC88473 injectionDrug: Placebo

Single dose of 35.7 mg HEC88473

EXPERIMENTAL

Healthy subjects, receiving a single dose of 35.7 mg HEC88473 (N=8) or placebo(N=2) after meal.

Drug: HEC88473 injectionDrug: Placebo

Single dose of 47.6 mg HEC88473

EXPERIMENTAL

Healthy subjects, receiving a single dose of 47.6 mg HEC88473 (N=8) or placebo(N=2) after meal.

Drug: HEC88473 injectionDrug: Placebo

Single dose of 62.9 mg HEC88473

EXPERIMENTAL

Healthy subjects, receiving a single dose of 62.9 mg HEC88473 (N=8) or placebo(N=2) after meal.

Drug: HEC88473 injectionDrug: Placebo

Single dose of 81.6 mg HEC88473

EXPERIMENTAL

Healthy subjects, receiving a single dose of 81.6 mg HEC88473 (N=8) or placebo(N=2) after meal.

Drug: HEC88473 injectionDrug: Placebo

Multiple doses of 5.1 mg HEC88473

EXPERIMENTAL

T2DM subjects, receiving a weekly dose of 5.1 mg HEC88473 (N=10) or placebo (N=2) for 5 consecutive weeks after meal.

Drug: HEC88473 injectionDrug: Placebo

Multiple doses of 15.3 mg HEC88473

EXPERIMENTAL

T2DM subjects, receiving a weekly dose of 15.3 mg HEC88473 (N=10) or placebo (N=2) for 5 consecutive weeks after meal.

Drug: HEC88473 injectionDrug: Placebo

Multiple doses of 30.6 mg HEC88473

EXPERIMENTAL

T2DM subjects, receiving a weekly dose of HEC88473 (N=10) or placebo (N=2) for 5 consecutive weeks after meal. The 30.6 mg cohort was administered by titration.

Drug: HEC88473 injectionDrug: Placebo

Multiple doses of 45.9 mg HEC88473

EXPERIMENTAL

T2DM subjects, receiving a weekly dose of HEC88473 (N=10) or placebo (N=2) for 5 consecutive weeks after meal. The 45.9 mg cohort was administered by titration.

Drug: HEC88473 injectionDrug: Placebo

Multiple doses of 68.0 mg HEC88473

EXPERIMENTAL

T2DM subjects, receiving a weekly dose of HEC88473 (N=10) or placebo (N=2) for 5 consecutive weeks after meal. The 68.0 mg cohort was administered by titration.

Drug: HEC88473 injectionDrug: Placebo

Interventions

HEC88473 injectionDRUG

HEC88473 will be provided as a 17 mg/mL solution and will be administered by subcutaneous injection in the abdomen.

Multiple doses of 15.3 mg HEC88473Multiple doses of 30.6 mg HEC88473Multiple doses of 45.9 mg HEC88473Multiple doses of 5.1 mg HEC88473Multiple doses of 68.0 mg HEC88473Single dose of 0.5 mg HEC88473Single dose of 1.7 mg HEC88473Single dose of 10.2 mg HEC88473Single dose of 17.0 mg HEC88473Single dose of 25.5 mg HEC88473Single dose of 35.7 mg HEC88473Single dose of 47.6 mg HEC88473Single dose of 5.1 mg HEC88473Single dose of 62.9 mg HEC88473Single dose of 81.6 mg HEC88473
PlaceboDRUG

Placebo will be administered by subcutaneous injection in the abdomen.

Multiple doses of 15.3 mg HEC88473Multiple doses of 30.6 mg HEC88473Multiple doses of 45.9 mg HEC88473Multiple doses of 5.1 mg HEC88473Multiple doses of 68.0 mg HEC88473Single dose of 0.5 mg HEC88473Single dose of 1.7 mg HEC88473Single dose of 10.2 mg HEC88473Single dose of 17.0 mg HEC88473Single dose of 25.5 mg HEC88473Single dose of 35.7 mg HEC88473Single dose of 47.6 mg HEC88473Single dose of 5.1 mg HEC88473Single dose of 62.9 mg HEC88473Single dose of 81.6 mg HEC88473

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Part A
  • Males or females, between 18 and 45 years of age, inclusive, at screening.
  • Body weight ≥ 50 kg for males and body weight ≥ 45 kg for females. 18≤body mass index (BMI)\<28 kg/m2 for nonobese subjects and 28≤BMI≤45 kg/m2 for obese subjects.
  • Part B
  • Males or females, between 18 and 65 years of age, inclusive, at screening.
  • kg/m2≤BMI≤35 kg/m2.
  • Subjects diagnosed with T2DM, newly diagnosed subjects at screening, or treated with diet and exercise alone within 3 months before screening and still have poor blood glucose control, or treated with a stable dose of metformin for ≥ 3 months before screening.
  • %≤ HbA1c ≤10.5% at screening.

You may not qualify if:

  • Part A
  • Smoked more than 5 cigarettes per day within 3 months before the study.
  • Immunization with a live attenuated vaccine or coronavirus vaccination within 1 month prior to screening or planned vaccination during the course of the study.
  • Positive alcohol breath test result or positive urine drug screen.
  • Blood donation (\> 300 mL) or massive blood loss (\> 400 mL) within 3 months before screening.
  • Part B
  • Have type 1 diabetes mellitus.
  • Have had ≥1 episode of severe hypoglycemia within 6 months before screening, or history of recurrent hypoglycemia (history of hypoglycemia more than 3 times in 3 months).
  • Have acute or chronic hepatitis, signs and symptoms of any other liver disease other than nonalcoholic fatty liver disease (NAFLD), or alanine aminotransferase (ALT) level \>5 times the upper limit of the reference range at screening.
  • Have serum calcitonin ≥20 ng/L at screening.
  • Have a personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2; or have hereditary diseases that can easily induce MTC.
  • Fasted triglycerides \> 5.7 mmol/L at screening. If the patient is on lipid-lowering therapies, doses must be stable for 30 days prior to screening.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

The First Hospital of Jilin University

Changchun, Jilin, 130000, China

Location

Related Publications (2)

  • Zhang H, Li Q, Chen H, Guo L, Li J, Xie C, Yan J, Ding Y. First-in-Human Study on Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Escalating Doses of HEC88473, a Novel Dual GLP-1 and FGF21 Receptor Agonist in Healthy and Obese Chinese Subjects. BioDrugs. 2025 May;39(3):477-486. doi: 10.1007/s40259-025-00715-3. Epub 2025 Apr 3.

    PMID: 40175670DERIVED

  • Xiang L, Wang G, Zhuang Y, Luo L, Yan J, Zhang H, Li X, Xie C, He Q, Peng Y, Chen H, Li Q, Li X, Guo L, Lv G, Ding Y. Safety and efficacy of GLP-1/FGF21 dual agonist HEC88473 in MASLD and T2DM: A randomized, double-blind, placebo-controlled study. J Hepatol. 2025 Jun;82(6):967-978. doi: 10.1016/j.jhep.2024.12.006. Epub 2024 Dec 19.

    PMID: 39709140DERIVED

MeSH Terms

Conditions

ObesityDiabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

OverweightOvernutritionNutrition DisordersNutritional and Metabolic DiseasesBody WeightSigns and SymptomsPathological Conditions, Signs and SymptomsDiabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesEndocrine System Diseases

Study Officials

  • Yanhua Ding, Doctor

    The First Hospital of Jilin University

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 5, 2023

First Posted

July 13, 2023

Study Start

August 11, 2021

Primary Completion

February 17, 2023

Study Completion

February 17, 2023

Last Updated

July 17, 2023

Record last verified: 2023-07

Locations

CN(1)