Glucokinase Activator in Monogenic Diabetes

Phase 2

Not yet recruiting

• Conditions: Diabetes Mellitus; Monogenic Diabetes
• Interventions: Drug: Dorzagliatin; Drug: matched placebo

• Registration Number: NCT06976658
• Lead Sponsor: Chinese University of Hong Kong

Brief Summary

Evaluating a novel, allosteric glucokinase activator in monogenic diabetes secondary to inactivating glucokinase mutations: a randomised, cross-over trial

Detailed Description

Evaluating a novel, allosteric glucokinase activator in monogenic diabetes secondary to inactivating glucokinase mutations: a randomised, cross-over trial

Study Timeline

• Study First Submitted: 2025-03-22
• Status Verified: 2025-05
• Study First Submitted QC: 2025-05-14
• Last Update Submitted: 2025-05-14
• Study First Posted: 2025-05-16
• Last Update Posted: 2025-05-16
• Study Start: 2025-05-28
• Primary Completion: 2026-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 44

Inclusion Criteria

1. Age ≥18 and <75 years
2. body mass index (BMI) >18 and <30 kg/m2
3. fasting plasma glucose >5.6 mmol/L at screening
4. Participants with GCK-MODY had and are heterozygous carriers of a pathogenic or likely pathogenic GCK mutation at screening based on guidelines published by the American College of Medical Genetics and Genomics (ACMG), Association for Clinical Genomic Science (ACGS) and the ClinGen Monogenic Diabetes Expert Panel (MDEP) .

Exclusion Criteria

1. Body weight <45kg at screening
2. Current or planning pregnancy or lactating
3. troke or cardiovascular disease within 6 months of recruitment
4. severe renal dysfunction (estimated glomerular filtration rate <30mL/min/1.73m2 or renal replacement therapy)
5. severe hepatic dysfunction (aspartate transaminase and/or alanine transaminase > 3 times upper limit of normal)
6. history of drug abuse or excessive alcohol intake
7. severe hypoglycemia within 6 months prior to screening
8. anaemia with Hb <10 g/dL at screening
9. excessive blood loss >300mL within 1 month of screening
10. use of strong or moderate CYP3A4 inhibitors or inducers
11. use of sulfonylureas, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 agonists, sodium glucose transporter 2 inhibitors, insulin, thiazolidinediones, acarbose in the 6 weeks prior to randomisation
12. use of long-term high-dose corticosteroids at randomisation
13. serious concurrent infections at time of screening

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Intervention	Dorzagliatin	active drug or placebo in a cross over randomised sequence
placebo	matched placebo	placebo in a cross over randomised sequence

Primary Outcome Measures

Name	Time	Method
Fasting plasma glucose	8 weeks	Difference in fasting plasma glucose (FPG) between treatment periods

Secondary Outcome Measures

Name	Time	Method
CGM metric coefficient of variation	8 weeks	Difference in % CV at end of treatment periods
Glucose area under the curve during OGTT	8 weeks	Difference between AUC glucose at end of treament periods
Insulin area under the curve during OGTT	8 weeks	Difference between AUC insulin at end of treament periods
GLP1 area under the curve during OGTT	8 weeks	Difference between AUC GLP-1 at end of treament periods
• HbA1c	8 weeks	Difference between HbA1c at end of treatment periods
CGM metrics time in range	8 weeks	Time in range defined by CGM at end of treatment periods

Trial Locations

Locations (1)

3M, Diabetes and Endocrine Research Center; 🇭🇰 Hong Kong, Hong Kong