Clinical trial NCT06047262: Dapansutrile in Diabetes and Diabetes-Related Complications - Dapan-Dia
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
Collaborators: name: European Union (Horizon Europe Programme)
name: State Secretariat for Education Research and Innovation, Switzerland
name: Olatec Therapeutics LLC
First posted: 2023-09-21
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: randomised controlled trial
Primary purpose: TREATMENT

Brief summary: The aim of the study is to determine whether NLRP3 inhibition with dapansutrile represents a new pharmacological option for diabetes management with potential as an anti-inflammatory agent to also address micro- and macro-vascular risk and complications from diabetes.

Detailed description: To date, no other oral NLRP3 inhibitor has sufficiently advanced in development to be tested in a chronic low-grade inflammatory disease such as type 2 diabetes mellitus over a period of 3 to 4 months as proposed in this trial. Based on the publicly available information, dapansutrile is the most advanced oral NLRP3 inhibitor in development. The rationale is built upon dapansutrile's clinical and extensive preclinical and safety findings, and from data in chronic animal toxicology studies to date, which together enable and support its investigation in select chronic low-grade inflammatory diseases. Therefore, the investigators have selected type 2 diabetes mellitus and its complications, including risk for cardiovascular disease, as a disease with clinical features of low-grade inflammation to further investigate the therapeutic potential of NLRP3 inhibition with dapansutrile.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of type 2, Diabetes mellitus 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
* HbA1c value of ≥ 7.7% to ≤ 11.0% at the Screening Visit.
* High-sensitivity C-reactive protein (hsCRP) ≥ 1.5 mg/L at the Screening Visit.
* Body mass index (BMI) ≥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

Exclusion Criteria:

* Diagnosis of type 1 diabetes mellitus
* HbA1c value of ≤ 7.5% or ≥ 10.5% at the Baseline Visit/Day 1, as determined at point of care (local laboratory)
* Use of thiazolidinediones (glitazones), pramlintide, or short-acting insulin/insulin analogues (as bolus or premixed insulin) within 12 weeks prior to the Screening Visit
* Less than 80% compliance in taking investigational medicinal product by pill count during the Run-In Period, as assessed at the Baseline Visit/Day 1
* 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
* Previous myocardial infarction, any cardiac surgery

Primary outcomes:
measure: Change in HbA1c in blood of patients for dapansutrile compared to placebo
timeFrame: two time assessment at baseline and week 26
Secondary outcomes:
measure: Change in HbA1c in blood of patients for dapansutrile compared to placebo
timeFrame: six time assessment at baseline and week 4, 8, 12, 16, 20
measure: Change in fasting plasma glucose for dapansutrile compared to placebo
timeFrame: seven time assessement at baseline and week 4, 8, 12, 16, 20, 26
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: Marc Y. Donath, Prof.
role: PRINCIPAL_INVESTIGATOR
References: