DAPANSUTRILE for Type 2 diabetes mellitus

Inclusion criteria

• {"criterion_text":"- Male and female adults age ≥ 18 and ≤ 75 years at the Screening Visit."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- High-sensitivity C-reactive protein (hsCRP) ≥ 1.5 mg/L at the Screening Visit."}
• {"criterion_text":"- Body mass index (BMI) between 25 to 40 kg/m2 at the Screening Visit."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Able and willing to provide written informed consent prior to initiation of any study-related procedures."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Fasting Glucose levels at run-in and baseline < 11 mmol/l (200 mg/dl)"}

Exclusion criteria

• {"criterion_text":"- 1)\tDiagnosis of type 1 diabetes mellitus."}
• {"criterion_text":"- 10)\tClinically 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."}
• {"criterion_text":"- 11)\tClinically 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)."}
• {"criterion_text":"- 12)\tThyroid stimulating hormone (TSH) outside of the normal range at the Screening Visit."}
• {"criterion_text":"- 13)\tEvidence/suspicion of an active infection including cellulitis."}
• {"criterion_text":"- 14)\tHistory 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"}
• {"criterion_text":"- 15)\tPositive test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, if tested, within 4 weeks of the Screening Visit"}
• {"criterion_text":"- 16)\tAny 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."}
• {"criterion_text":"- 17)\tCurrent use of any of the following medications or any other prohibited medications per Table 4-2: a.\tOral 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.\tAny 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.\tColchicine or sulfasalazine. Low-dose aspirin for cardiovascular disease or anti-thrombotic prophylaxis is allowed. d.\tBile acid sequestrants (e.g., cholestyramine or colestipol)."}
• {"criterion_text":"- 18)\tWoman of childbearing potential, or man whose sexual partner(s) is a woman of childbearing potential, who: a.\tIs 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.\tIs lactating/breastfeeding or plans to breastfeed while participating in the study (female subjects only) c.\tIs 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)."}
• {"criterion_text":"- 19)\tAny 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."}
• {"criterion_text":"- 2)\tHbA1c value of ≤ 7.5% or ≥ 10.5% at the Baseline Visit/Day 1, as determined at point of care (local laboratory)."}
• {"criterion_text":"- 20)\tHistory 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."}
• {"criterion_text":"- 21)\tEnrolment in any trial investigating a medicinal product within 3 months prior to the Screening Visit."}
• {"criterion_text":"- 22)\tActive malignancy or recent malignancy with any systemic anti-cancer treatment (e.g., immunotherapy or chemotherapy) within 6 months prior to the Screening Visit."}
• {"criterion_text":"- 23)\tHas a serious illness that resulted in hospitalisation within 30 days prior to the Screening Visit."}
• {"criterion_text":"- 24)\tHas a hypersensitivity or allergy to dapansutrile or other drugs in its class and/or the components of the IMP (dapansutrile tablets or placebo tablets)."}
• {"criterion_text":"- 25)\tIs an employee, family member, or student of the Investigator or study site."}
• {"criterion_text":"- 26)\tFor substudy participants only: Has a contraindication to undergoing magnetic resonance [MR]-based assessments. Note: The substudy will only be conducted at select study sites."}
• {"criterion_text":"- 3)\tUse 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."}
• {"criterion_text":"- 4)\tLess 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."}
• {"criterion_text":"- 5)\tSignificant weight loss (> 5 kg) in the 12 weeks prior to the Screening Visit"}
• {"criterion_text":"- 6)\tSystolic 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."}
• {"criterion_text":"- 7)\tPrevious 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."}
• {"criterion_text":"- 8)\tClinical symptoms compatible with New York Heart Association (NYHA) class III or IV heart failure."}
• {"criterion_text":"- 9)\tKnown 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)."}

Primary endpoints

• {"endpoint_text":"- Change from baseline in HbA1c at Week 26 for dapansutrile compared to placebo.","definition_or_measurement_approach":"Change from baseline in HbA1c measured at Week 26 compared between dapansutrile and placebo."}

Secondary endpoints

• {"endpoint_text":"- Change from baseline in body weight and body mass index at weeks 4, 8, 12, 16, 20 and 26","definition_or_measurement_approach":"Change from baseline in body weight and BMI measured at weeks 4, 8, 12, 16, 20 and 26."}
• {"endpoint_text":"- Change from baseline in body waist-to-hip ratio and waist-to-height ratio at weeks 8 and 26","definition_or_measurement_approach":"Change from baseline in waist-to-hip ratio and waist-to-height ratio measured at weeks 8 and 26."}
• {"endpoint_text":"- Change from baseline in HbA1c at Weeks 4, 8, 12, 16, and 20","definition_or_measurement_approach":"Change from baseline in HbA1c measured at Weeks 4, 8, 12, 16 and 20."}
• {"endpoint_text":"- Change from baseline in fasting plasma glucose at Weeks 4, 8, 12, 16, 20, and 26","definition_or_measurement_approach":"Change from baseline in fasting plasma glucose measured at specified weeks."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"β-cell responsivity index and insulin sensitivity (Si) derived by mathematical modelling of glucose, insulin and C-peptide after a standardized 2-hour mixed-meal tolerance test at Weeks 8 and 26."}
• {"endpoint_text":"- Change from baseline in fasting proinsulin to insulin ratio at Weeks 8 and 26","definition_or_measurement_approach":"Change in fasting proinsulin:insulin ratio measured at Weeks 8 and 26."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Continuous glucose monitoring (CGM) assessment at Week 26 reporting percent time in target range (3.4-10.0 mmol/l), time below target (2.6-3.3 mmol/l and <2.6 mmol/l), and time above target."}

Belgium

Earliest CTIS Part Ii Submission Date

26-09-2024

Latest Decision Or Authorization Date

20-02-2026

Processing Time Days

512

Number Of Sites

1

Number Of Participants

45

France

Earliest CTIS Part Ii Submission Date

28-10-2024

Latest Decision Or Authorization Date

25-02-2026

Processing Time Days

485

Number Of Sites

2

Number Of Participants

110

Germany

Earliest CTIS Part Ii Submission Date

19-12-2024

Latest Decision Or Authorization Date

23-03-2026

Processing Time Days

459

Number Of Sites

1

Number Of Participants

75

Primary sponsor

Full Name

Kantonsspital Baden AG

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Switzerland

Third parties

• {"country":"Germany","full_name":"Ivers-Lee AG","duties_or_roles":"Sponsor duties codes: 14, 9; contact: j.mueller@il-csm.de","organisation_type":"SME"}