2024-511828-14-00招募中2 期
A Multi-Centre, Randomised, Double-Blind, Placebo-Controlled Trial of the Safety and Efficacy of the Oral NLRP3 Inhibitor Dapansutrile in Subjects with Type 2 Diabetes Mellitus Dapan-Dia Study
Universitaetsspital Basel3 个研究点 分布在 3 个国家目标入组 230 人开始时间: 2025年1月13日最近更新:
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 230
- 试验地点
- 3
- 主要终点
- Change from baseline in HbA1c at Week 26 for dapansutrile compared to placebo.
研究概览
简要总结
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.
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Male and female adults age ≥ 18 and ≤ 75 years at the Screening Visit.
- •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
- •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).
- •High-sensitivity C-reactive protein (hsCRP) ≥ 1.5 mg/L at the Screening Visit.
- •Body mass index (BMI) between 18 to 40 kg/m2 at the Screening Visit.
- •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.
- •Able and willing to provide written informed consent prior to initiation of any study-related procedures.
- •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.
- •Fasting Glucose levels at run-in and baseline < 9 mmol/l (162 mg/dl)
排除标准
- •Diagnosis of type 1 diabetes mellitus.
- •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.
- •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).
- •Thyroid stimulating hormone (TSH) outside of the normal range at the Screening Visit.
- •Evidence/suspicion of an active infection including cellulitis.
- •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
- •Positive test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, if tested, within 4 weeks of the Screening Visit
- •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.
- •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).
- •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).
- •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.
- •HbA1c value of ≤ 7.5% or ≥ 10.5% at the Baseline Visit/Day 1, as determined at point of care (local laboratory).
- •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.
- •Enrolment in any trial investigating a medicinal product within 3 months prior to the Screening Visit.
- •Active malignancy or recent malignancy with any systemic anti-cancer treatment (e.g., immunotherapy or chemotherapy) within 6 months prior to the Screening Visit.
- •Has a serious illness that resulted in hospitalisation within 30 days prior to the Screening Visit.
- •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).
- •Is an employee, family member, or student of the Investigator or study site.
- •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.
- •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.
- •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
- •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.
- •Significant weight loss (> 5 kg) in the 12 weeks prior to the Screening Visit
- •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.
- •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.
- •Clinical symptoms compatible with New York Heart Association (NYHA) class III or IV heart failure.
- •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).
结局指标
主要结局
Change from baseline in HbA1c at Week 26 for dapansutrile compared to placebo.
Change from baseline in HbA1c at Week 26 for dapansutrile compared to placebo.
次要结局
- Change from baseline in HbA1c at Weeks 4, 8, 12, 16, and 20
- Change from baseline in fasting plasma glucose at Weeks 4, 8, 12, 16, 20, and 26
- 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
- Change from baseline in fasting proinsulin to insulin ratio at Weeks 8 and 26
- 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.
研究者
Prof Dr Marc Y. Donath
Scientific
Kantonsspital Baden AG
研究点 (3)
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