Investigating How NNC0487-0111 Regulates Insulin of Adults With Type 2 Diabetes

Official title

Effect of NNC0487-0111 on Insulin Sensitivity and Pancreatic Endocrine Function in Adults With Type 2 Diabetes

Overview

The purpose of this clinical study is to find out how NNC0487-0111 affects, how the body uses insulin (a hormone that helps the body control blood sugar) and how well the pancreas works in people living with type 2 diabetes. There are 2 study treatments. Participants will get either NNC0487-0111 (the treatment being tested) or Placebo (a treatment that has no active medicine in it). Which treatment participants get is decided by chance.

Interventions

• Drug NNC0487-0111
  NNC0487-0111 will be administered subcutaneously using PDS290 pre-filled pen-injectors to the abdomen.
• Drug Placebo
  Placebo matched to NNC0487-0111 will be administered subcutaneously using PDS290 pre-filled pen-injectors to the abdomen.

Primary outcome measures

• Change in M-value in Hyperinsulinaemic euglycaemic clamp (HEC) [Time frame: Baseline to week 40]

Secondary outcome measures (11)

• Change in M-value in HEC, normalised by lean body mass [Time frame: Baseline to week 40]
• Change in first-phase incremental Insulin Secretion Rate (ISR0-8 min) in Hyperglycaemic clamp (HGC) [Time frame: Baseline to week 40]
• Change in second-phase ISR (ISR20-120 min) in HGC [Time frame: Baseline to week 40]
• Change in total ISR (ISR0-120 min) in HGC [Time frame: Baseline to week 40]
• Change in ISR at fixed glucose concentration (ISRg) in HGC [Time frame: Baseline to week 40]
• Change in total insulin response [total area under curve (AUC0-120) min] in HGC [Time frame: Baseline to week 40]
• Change in clamp disposition index (cDI) calculated from HEC and HGC [Time frame: Baseline to week 40]
• Change in cDI calculated from HEC and HGC, based on lean body mass [Time frame: Baseline to week 40]
• Change in β-cell glucose sensitivity (insulin secretion) from HGC [Time frame: Baseline to week 40]
• Change in β-cell glucose sensitivity from mixed meal tolerance test (MMTT) (slope of dose-response for insulin secretion vs. plasma glucose) [Time frame: Baseline to week 40]
• Change in glycated haemoglobin (HbA1c) [Time frame: Baseline to week 40]

Eligibility criteria

Inclusion criteria

• Male or female.
• Age 18-75 years (both inclusive) at the time of signing the informed consent.
• Diagnosed with type 2 diabetes more than or equal to (≥)180 days before screening.
• Only stable daily dose(s) of metformin at effective or maximum tolerated dose, as judged by the investigator for at least 90 days before screening. If additional oral antidiabetic drug (OAD) is required, only stable dose(s) of sodium-glucose cotransporter-2 inhibitors (SGLT2i) is permitted, and this must also have been maintained for at least 90 days before screening.
• HbA1c at screening of 6.5-9.5% \[48-80 millimole per mole (mmol/mol)\] (both inclusive) if on metformin only, or 6.0-9.0% (42-75 mmol/mol) (both inclusive) if on metformin in combination with SGLT2i.

Exclusion criteria

• Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using highly effective contraceptive method.
• Presence of type 1 diabetes.
• Any clinically significant body weight change (≥5% self-reported change) or dieting attempts (e.g., participation in a weight reduction program) within 90 days before screening.
• Treatment with any medication for the indication of T2D or weight management other than stated in the inclusion criteria within 90 days before screening. However, short term insulin treatment for a maximum of 14 consecutive days and prior insulin treatment for gestational diabetes are allowed.
• Treatment with a GLP-1 receptor agonist.
• Participant with diabetic retinopathy or maculopathy who received treatment with retinal photocoagulation, vitrectomy or anti-Vascular Endothelial Growth Factor (anti-VEGF) before screening or are expected to require treatment after screening. Diabetic retinopathy or maculopathy must be verified by an eye examination performed within 90 days before screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.
• Presence or history of cardiovascular disease including stable and unstable angina pectoris, myocardial infarction, transient ischaemic attack, stroke, cardiac decompensation, clinically significant arrhythmias or clinically significant conduction disorders within 180 days before screening.
• Renal impairment with estimated glomerular filtration rate (eGFR) less than (<) 60.0 milliliter per minute per meter square (ml/min/1.73 m\^2) at screening.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Germany · 1 center

• Profil Institut für Stoffwechselforschung GmbH — Neuss

Identifiers

NCT: NCT07535307 · NN9490-8153 · U1111-1320-4780 · 2025-521595-55

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗