A First in Human (FIH) Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DR10624

A Phase 1, Randomized, Placebo-Controlled, Double-Blind Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single-and-Multiple-Ascending Subcutaneous Doses of DR10624

DR10624 is an Fc fusion protein tri-agonist with balanced glucagon-like peptide-1 receptor (GLP-1R)/glucagon receptor (GCGR)/ fibroblast growth factor 21 receptor (FGF21R) agonizing activities. The objectives of the planned clinical investigation will be to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single- and multiple-ascending doses of DR10624 via subcutaneous (SubQ) injection in a randomized, placebo-controlled, double-blind study.

Study Overview

• Status: Completed
• Conditions: Healthy, Obesity, Metabolically
• Intervention / Treatment: Drug: DR10624 for injection; Drug: Placebo

Detailed Description

This study includes 2 parts( 1 and 2). Part 1 involves a single dose of DR10624 taken as a subcutaneous injection just under the skin. Part 2 involve multiple doses of DR10624 taken as a subcutaneous injection (SC) just under the skin. Each participant will enroll in only one part.

• Study Type: Interventional
• Enrollment (Actual): 153
• Phase: Phase 1

Contacts and Locations

Study Locations

• New Zealand
  • Canterbury
    • Christchurch, Canterbury, New Zealand, 8011
      • New Zealand Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. The subject is considered by the investigator to be in good general health as determined by medical history, clinical laboratory test results, vital sign measurements, 12-lead ECG results, and physical examination findings at screening.

2. Female subjects (heterosexually active, of childbearing potential, not pregnant, not trying to become pregnant, and not lactating) are eligible to participate if they agree to total abstinence from heterosexual intercourse or use a highly effective method of birth control listed below, from screening through until at least 30 days after the last dose of the study drug.

   Male subjects with female partners of childbearing potential are eligible to participate if they are vasectomized, or agree to total abstinence from heterosexual intercourse, from screening through until at least 30 days after the last study dose, or use of an effective method of birth control listed above, from screening through until at least 30 days after the last study dose. Male subjects must refrain from sperm donation throughout the study and for 30 days after the last study dose.

3. The subject agrees to comply with all protocol requirements.
4. The subject is able to provide written informed consent.

Additional inclusion criteria for Part 1:

1. The subject is male or female 18 to 55 years of age, inclusive.
2. The subject has a body weight ≥50 kg at screening and a BMI of 18 to 32 kg/m2, inclusive, or.
3. The subject has a BMI of 30 to 40 kg/m2, inclusive, at screening in obesity subjects cohort.

Additional inclusion criteria for Part 2:

1. The subject is male or female 18 to 60 years of age, inclusive.
2. The subject has a BMI of 30 to 45 kg/m2 at screening, inclusive.
3. Fasting triglyceride ≥150 mg/dL (1.7 mmol/L), and <500 mg/dL (5.7 mmol/L), at screening.

Exclusion Criteria:

1. The subject has a positive test result for hepatitis B surface antigen, hepatitis C virus antibody, or human immunodeficiency virus types 1 or 2 antibodies at screening.
2. The subject has a personal or family history of medullary thyroid cancer, or multiple endocrine neoplasia syndrome Type 2, or a screening calcitonin ≥50 ng/L.
3. The subject has a history of chronic pancreatitis or episode of acute pancreatitis within 3 months of screening.
4. In Part 1, the subject has used any prescription medications (excluding oral contraceptives, paracetamol, and ibuprofen) within 14 days before the first dose of study drug. In Part 2, the subjects have been on stable lipid-lowering therapy <8 weeks before the first dose of study drug.
5. The subject has consumed alcohol within 48 hours before dosing or during the confinement period.
6. The subject is a smoker or has used tobacco, nicotine, or nicotine-containing products.
7. The subject has a history of alcohol abuse or drug addiction within the last year or excessive alcohol consumption.
8. The subject has a positive test result for drugs of abuse and/or alcohol abuse at screening and check-in for the first inpatient period.
9. The subject is involved in strenuous activity or contact sports within 48 hours before admission.
10. The subject has donated blood or blood products >450 mL within 30 days before the first dose of study drug.
11. The subject has total cholesterol >10.3 mmol/L or triglycerides ≥5.7 mmol/L (500 mg/dL) at screening.

12. The subject has clinically significant history or presence of ECG findings as determined by the investigator at screening and check-in,

    - Uncontrolled hypertension (defined as systolic blood pressure (SBP) ≥160 mmHg, and/or diastolic blood pressure (DBP) ≥100 mmHg), angina, bradycardia (if assessed as clinically significant by the investigator), or severe peripheral arterial circulatory disorders.

13. The subject has a history of relevant drug and/or food allergies (ie, allergy to DR10624 or excipients, or any significant food allergy that could preclude a standard diet in the clinical unit).
14. The subject has a history of severe allergic or anaphylactic reactions.
15. The subject has experienced a >5% loss in body weight within 2 months prior to screening.
16. Female subjects who are pregnant or lactating.
17. The subject has a positive test for severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). A positive rapid antigen test (RAT), isothermal nucleic acid amplification, or polymerase chain reaction (PCR) coronavirus disease-2019 (COVID-19) test during screening or at admission is acceptable provided the subject has a known previous COVID-19 infection ≥3 weeks prior to dosing, has recovered, and is now asymptomatic
18. The subject has received study drug in another investigational study within 30 days of dosing.
19. In the opinion of the investigator, the subject is not suitable for entry into the study.

Additional exclusion criteria for subjects in Part 2:

1. Subjects with coagulopathies.
2. Poorly controlled diabetes, defined as HbA1c >8.5% at screening.
3. The subject has been treated with the following anti-diabetic agents, glucagon-like peptide-1 receptor agonist (GLP-1Ra), dipeptidyl peptidase-4 inhibitors (DPP-4i), or insulin, within 30 days prior to screening until the follow-up visit.
4. The subjects have >2 × upper limit of normal (ULN) of either alanine aminotransferase (ALT) or aspartate aminotransferase (AST), or >1.5 × ULN for bilirubin or alkaline phosphatase at screening.
5. Subjects with contraindications to MRI.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single-ascending dose：Part1：DR10624; Escalating doses of DR10624 for injection administered subcutaneously in healthy participants or obese but otherwise healthy participants	Drug: DR10624 for injection; administered via subcutaneous injection
Placebo Comparator: Single-ascending dose：Part1：placebo; Escalating doses of placebo for injection administered subcutaneously in in healthy participants or obese but otherwise healthy participants	Drug: Placebo; administered via subcutaneous injection
Experimental: Multiple-ascending dose：Part2：DR10624; Escalating doses of DR10624 for injection administered subcutaneously in obese adult subjects with moderate hypertriglyceridemia	Drug: DR10624 for injection; administered via subcutaneous injection
Placebo Comparator: Multiple-ascending dose：Part2：placebo; Escalating doses of placebo for injection administered subcutaneously in obese adult subjects with moderate hypertriglyceridemia	Drug: Placebo; administered via subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with one or more treatment-emergent adverse event (TEAE), serious adverse event (SAE) and adverse event of special interest (AESI).	Number of participants with one or more TEAE, SAE and AESI.	baseline through day 29(part 1)or day 106(part 2)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the serum concentration versus time curve (AUC)	Area under the serum concentration versus time curve (AUC)	baseline through day 29(part 1)or day 106(part 2)
Maximum observed serum concentration (Cmax)	Maximum observed serum concentration (Cmax)	baseline through day 29(part 1)or day 106(part 2)
Time to reach maximum observed serum concentration (Tmax)	Time to reach maximum observed serum concentration (Tmax)	baseline through day 29(part 1)or day 106(part 2)
Terminal elimination half-life (t1/2)	Terminal elimination half-life (t1/2)	baseline through day 29(part 1)or day 106(part 2)
Mean residence time (MRT)	Mean residence time (MRT)	baseline through day 29(part 1)or day 106(part 2)
Apparent clearance after extravascular administration (CL/F)	Apparent clearance after extravascular administration (CL/F)	baseline through day 29(part 1)or day 106(part 2)
Apparent volume of distribution during the terminal elimination phase after extravascular administration (Vz/F)	Apparent volume of distribution during the terminal elimination phase after extravascular administration (Vz/F)	baseline through day 29(part 1)or day 106(part 2)
AUC from time 0 to the time of the dosing interval (AUC0-t)	AUC from time 0 to the time of the dosing interval (AUC0-t)	baseline through day 106(part 2)
Accumulation ratio (AR)	Accumulation ratio (AR)	baseline through day 106(part 2)
Predose concentrations(Ctrough)	Predose concentrations(Ctrough)	baseline through day 106(part 2)
change in body weight	change in body weight	baseline through Day 85
change in adiponectin	change in adiponectin	baseline through Day 85
change in BMI	change in BMI	baseline through Day 85
change in waist circumference	change in waist circumference	baseline through Day 85
change in fasting lipid profile	change in fasting lipid profile	baseline through Day 85
change in fasting plasma glucose (FPG)	change in FPG	baseline through Day 85
change in HbA1c	change in HbA1c	baseline through Day 85
change in C-peptide	change in C-peptide	baseline through Day 85
change in fasting insulin	change in fasting insulin	baseline through Day 85
change in glucagon	change in glucagon	baseline through Day 85
change in homeostatic model assessment index of insulin resistance (HOMA-IR) and homeostatic model assessment index of beta-cell function (HOMA-B)	change in HOMA-IR and HOMA-B	baseline through Day 85
change in Partial area glucose level versus time curve from time 0 to 4 hours (△AUC0-4h)	change in Partial area glucose levels versus time curve from time 0 to 4 hours (△AUC0-4h)	baseline through Day 85
change in Partial area insulin level versus time curve from time 0 to 4 hours (△AUC0-4h)	change in Partial area insulin levels versus time curve from time 0 to 4 hours (△AUC0-4h)	baseline through Day 85
change in Partial area C-peptide level versus time curve from time 0 to 4 hours (△AUC0-4h)	change in Partial area C-peptide levels versus time curve from time 0 to 4 hours (△AUC0-4h)	baseline through Day 85
change in Partial area glucagon level versus time curve from time 0 to 4 hours (△AUC0-4h)	change in Partial area glucagon levels versus time curve from time 0 to 4 hours (△AUC0-4h)	baseline through Day 85
change percentage of time spent of glucose in target range 3.9 to 10 mmol/L (TIR), time above target range (TAR), time below target range (TBR), 24-hour mean glucose, and glucose variability	change in TIR, TAR, TBR, 24-hour mean glucose, and glucose variability	baseline through Day 85
change in hepatic fat fraction measured by magnetic resonance imaging-proton density fat fraction (MRI-PDFF ) in part 2	change in hepatic fat fraction measured by MRI-PDFF in part 2	baseline through Day 85
Change in liver stiffness by FibroScan in subjects with baseline hepatic fat of at least 8%	Change in liver stiffness by FibroScan in subjects with baseline hepatic fat of at least 8%	baseline through Day 85
Change in the liver function parameters (ALT, AST, alkaline phosphatase (ALP), and gamma-glutamyltransferase (GGT))	Change in the liver function (ALT, AST, alkaline phosphatase (ALP), and gamma-glutamyltransferase (GGT))	baseline through Day 85
Change in Fibrosis 4 score (FIB-4) and non-alcoholic fatty liver disease fibrosis score (NFS)	Change in FIB-4 and NFS	baseline through Day 85

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of hypoglycemic events per week	Rate of hypoglycemic events per week (overall and night-time event rates) in T2D subjects at baseline and following multiple SubQ doses of DR10624	24 months

Collaborators and Investigators

• Sponsor: Zhejiang Doer Biologics Co., Ltd.
• Investigators: Study Chair: Yanshan Huang, PhD, Zhejiang Doer Biologics Co., Ltd.; Study Director: Junfang Xu, MD, Huadong Medicine Co., Ltd.; Principal Investigator: Alexandra Cole, DHPharm, New Zealand Clinical Research (NZCR); Study Director: Yongliang Fang, PhD, Zhejiang Doer Biologics Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2022
• Primary Completion (Actual): October 10, 2024
• Study Completion (Actual): January 31, 2025

Study Registration Dates

• First Submitted: March 25, 2022
• First Submitted That Met QC Criteria: May 12, 2022
• First Posted (Actual): May 18, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 1, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Obese, obese with metabolic syndrome, Type 2 Diabetes
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Insulin Resistance; Hyperinsulinism; Diabetes Mellitus, Type 2; Metabolic Syndrome
• Other Study ID Numbers: DR10624-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No