Dapansutrile in Diabetes and Diabetes-Related Complications - Dapan-Dia Trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Kantonsspital Baden AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

13 May 2025 → ongoing

Decision date (initial)

2025-01-13

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-511828-14-00

ClinicalTrials.gov

NCT06047262

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

Primary Objective:
- To evaluate the efficacy of dapansutrile as add-on therapy when compared to placebo in lowering HbA1c after 26 weeks of treatment in subjects with T2DM that is inadequately controlled on standard-of-care anti-diabetic therapy.

Secondary objectives 3

1. To assess the effect of dapansutrile compared to placebo on body weight, body mass index and waist-to-hip ratio and waist-to-height ratio
2. To assess the effect of dapansutrile compared to placebo on β-cell secretory function, insulin resistance, and glycaemic parameters
3. To assess the safety and tolerability of dapansutrile relative to placebo

Conditions and MedDRA coding

Type II diabetes melittus (10067585)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Male and female adults age ≥ 18 and ≤ 75 years at the Screening Visit.
2. Diagnosis of T2DM as defined by the criteria of the American Diabetes Association (ADA) Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (see Appendix 1) and recognized by the World Health Organization (WHO, 2019), for at least 3 months prior to the Baseline Visit/Day 1.
3. HbA1c value of ≥ 7.7% to ≤ 11.0% at the Screening Visit. Note: Refer to Exclusion Criterion #2) for further HbA1c criteria (assessed at the Baseline Visit/Day 1).
4. High-sensitivity C-reactive protein (hsCRP) ≥ 1.5 mg/L at the Screening Visit.
5. Body mass index (BMI) between 25 to 40 kg/m2 at the Screening Visit.
6. Acceptable overall medical condition to safely participate in the study and complete all study procedures (particularly with regard to cardiovascular, renal, and hepatic conditions), in the opinion of the Investigator.
7. Able and willing to provide written informed consent prior to initiation of any study-related procedures.
8. Ability, in the opinion of the Investigator, to understand and comply with all the requirements of the study, which includes the ability to use CGM and to complete the 2 hour mixed-meal tolerance test (MMT). Note: The MMT at the Week 8 Visit is optional. Thus, subjects who are willing to perform an MMT only at the Baseline Visit/Day 1 and Week 26 Visit may be enrolled.
9. Fasting Glucose levels at run-in and baseline < 11 mmol/l (200 mg/dl)

Exclusion criteria 26

1. 1) Diagnosis of type 1 diabetes mellitus.
2. 2) HbA1c value of ≤ 7.5% or ≥ 10.5% at the Baseline Visit/Day 1, as determined at point of care (local laboratory).
3. 3) Use of thiazolidinediones (glitazones), pramlintide, or short-acting insulin/insulin analogues (as bolus or premixed insulin) within 12 weeks prior to the Screening Visit. Note: Basal (long-acting) insulin, glucagon-like peptide 1 (GLP-1) receptor agonists, dual glucose-dependent insulinotropic polypeptide (GIP)-GLP-1 receptor agonists, sodium-glucose cotransporter-2 (SGLT2) inhibitors, dipeptidyl peptidase (DPP)-IV inhibitors, metformin, and sulfonylureas are permitted.
4. 4) Less than 80% compliance in taking IMP (placebo tablets) by pill count during the Single-Blind Run-In Period, as assessed at the Baseline Visit/Day 1. Note: If compliance is < 80% over the 4-week run-in interval due to a significant life event, the run-in interval may be extended by 2 weeks at the discretion of the Investigator, but then the subject must have ≥ 90% compliance during the final 2 weeks of the Single-Blind Run-In Period to be considered eligible.
5. 5) Significant weight loss (> 5 kg) in the 12 weeks prior to the Screening Visit
6. 6) Systolic blood pressure (BP) ≥ 160 mmHg, diastolic BP ≥ 100 mmHg, or resting heart rate (HR) ≥ 100 beats/minute at the Screening Visit. Note: Subjects not meeting BP criteria may be re-screened once within 4 weeks of the initial assessment.
7. 7) Previous myocardial infarction, any cardiac surgery (including percutaneous transluminal coronary angioplasty), coronary artery bypass graft, a documented history of unstable angina, or a cerebrovascular accident within 6 months prior to the Screening Visit.
8. 8) Clinical symptoms compatible with New York Heart Association (NYHA) class III or IV heart failure.
9. 9) Known diagnosis of advanced chronic kidney disease or known history of renal impairment (e.g., estimated glomerular filtration rate [eGFR] < 45 mL/min/1.73 m2, according to Modification of Diet in Renal Disease [MDRD] equation).
10. 10) Clinically significant hepatic disease or alanine aminotransferase (ALT)/aspartate aminotransferase (AST) > 3.5 × the upper limit of the normal (ULN) reference range or total bilirubin > 1.5 × ULN (other than Gilbert’s syndrome) at the Screening Visit.
11. 11) Clinically significant anaemia (i.e., haemoglobin concentration < 12.0 g/dL for males or < 11.0 g/dL for females) at the Screening Visit or known diagnosis of haemoglobinopathies (e.g., sickle cell anaemia or thalassaemia).
12. 12) Thyroid stimulating hormone (TSH) outside of the normal range at the Screening Visit.
13. 13) Evidence/suspicion of an active infection including cellulitis.
14. 14) History of, or known positive for, human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or antibodies to hepatitis C virus (HCV) with a positive polymerase chain reaction (PCR) result for HCV
15. 15) Positive test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, if tested, within 4 weeks of the Screening Visit
16. 16) Any concurrent conditions or any clinically significant abnormalities identified on the screening physical examination, laboratory tests, or electrocardiogram (ECG) that, in the opinion of the Investigator, may affect the interpretation of the study results, or would otherwise contraindicate participation in a clinical study with a new chemical entity.
17. 17) Current use of any of the following medications or any other prohibited medications per Table 4-2: a. Oral or injectable corticosteroids (topical hydrocortisone and inhaled corticosteroids are permitted; replacement dosing [15 mg or less hydrocortisone] for primary or secondary adrenal insufficiency is permitted). b. Any drugs specifically targeting the immune system (e.g., tumour necrosis factor [TNF]- blockers, canakinumab, anakinra, rituximab, abatacept, tocilizumab) or oral immune-suppressants (e.g., Janus kinase [JAK] inhibitors, tyrosine kinase 2 [TYK2] inhibitors, methotrexate, hydroxychloroquine). c. Colchicine or sulfasalazine. Low-dose aspirin for cardiovascular disease or anti-thrombotic prophylaxis is allowed. d. Bile acid sequestrants (e.g., cholestyramine or colestipol).
18. 18) Woman of childbearing potential, or man whose sexual partner(s) is a woman of childbearing potential, who: a. Is or intends to become pregnant (including use of fertility drugs) while participating in the study (i.e., through the Week 30 follow-up call) b. Is lactating/breastfeeding or plans to breastfeed while participating in the study (female subjects only) c. Is not willing to use an acceptable, highly effective method of contraception until all follow-up procedures are complete (see Section 4.11.2 for more details on acceptable forms of contraceptives and required duration of use).
19. 19) Any other concomitant medical or psychiatric conditions, diseases, or prior surgeries that, in the opinion of the Investigator, would impair the subject from safely participating in the trial and/or completing protocol requirements.
20. 20) History of alcohol or substance abuse within 12 months prior to the Screening Visit or an Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) score ≥ 5 at the Screening Visit.
21. 21) Enrolment in any trial investigating a medicinal product within 3 months prior to the Screening Visit.
22. 22) Active malignancy or recent malignancy with any systemic anti-cancer treatment (e.g., immunotherapy or chemotherapy) within 6 months prior to the Screening Visit.
23. 23) Has a serious illness that resulted in hospitalisation within 30 days prior to the Screening Visit.
24. 24) Has a hypersensitivity or allergy to dapansutrile or other drugs in its class and/or the components of the IMP (dapansutrile tablets or placebo tablets).
25. 25) Is an employee, family member, or student of the Investigator or study site.
26. 26) For substudy participants only: Has a contraindication to undergoing magnetic resonance [MR]-based assessments. Note: The substudy will only be conducted at select study sites.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline in HbA1c at Week 26 for dapansutrile compared to placebo.

Secondary endpoints 7

1. Change from baseline in body weight and body mass index at weeks 4, 8, 12, 16, 20 and 26
2. Change from baseline in body waist-to-hip ratio and waist-to-height ratio at weeks 8 and 26
3. Change from baseline in HbA1c at Weeks 4, 8, 12, 16, and 20
4. Change from baseline in fasting plasma glucose at Weeks 4, 8, 12, 16, 20, and 26
5. Change from baseline in β-cell secretory function (β-cell responsivity index) and insulin sensitivity (Si) derived by mathematical modelling of glucose, insulin, and C-peptide after a 2-hour standardized MMT at Weeks 8 and 26
6. Change from baseline in fasting proinsulin to insulin ratio at Weeks 8 and 26
7. Change from baseline in glycaemic control (3.4-10.0 mmol/l), measured as percentage of time spent in target glycaemic range, below target range (hypoglycaemia levels between 2.6-3.3 mmol/l and below 2.6 mmol/l), and above target range (hyperglycaemia) as assessed by CGM at Week 26

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Kantonsspital Baden AG

Sponsor organisation

Kantonsspital Baden AG

Address

Im Ergel 1

City

Baden

Postcode

5404

Country

Switzerland

Scientific contact point

Organisation

Kantonsspital Baden AG

Contact name

Prof Dr Marc Y. Donath

Public contact point

Organisation

Kantonsspital Baden AG

Contact name

Prof Dr Marc Y. Donath

Third parties 1

Locations

3 EU/EEA countries · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 18 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications