Effects of Cofrogliptin on Beta-Cell Function in LADA Patients

Официальное название

Key Effects of Cofrogliptin on Beta-cell Function in Adults With Latent Autoimmune Diabetes (LADA): A Single-Center, Randomized, Controlled Trial - KOLA Study

Обзор

This single-center, randomized, open-label, controlled study aims to evaluate the effect of cofrogliptin on pancreatic β-cell function in adults with latent autoimmune diabetes in adults (LADA). Following a screening period of up to 6 weeks, 84 eligible participants will be randomized in a 1:1 ratio via a sealed-envelope method, stratified by baseline GADA titer (≥0.3 vs \<0.3). Participants will be assigned to one of two treatment arms: (1) metformin (with or without insulin) plus vitamin D3, or (2) metformin (with or without insulin) plus vitamin D3 and cofrogliptin. Cofrogliptin will be administered orally at a dose of 10 mg once every 2 weeks, and vitamin D3 at 2000 IU once daily, for a total treatment duration of 52 weeks. Study visits are planned at baseline and at Weeks 12, 26, 38, and 52, during which mixed-meal tolerance tests (MMTT) and other protocol-specified assessments will be conducted.

Подробное описание

Latent autoimmune diabetes in adults (LADA) is a form of autoimmune diabetes characterized by the progressive destruction of pancreatic beta cells. Preclinical and clinical evidence suggests that dipeptidyl peptidase-4 (DPP-4) inhibitors and vitamin D possess immunomodulatory effects that may help preserve residual beta-cell function. Cofrogliptin is a novel, ultra-long-acting DPP-4 inhibitor.

This study will enroll patients with LADA who will first enter a screening period. Eligible participants will be randomized (1:1) into two parallel arms on Day 1. The experimental group will receive cofrogliptin and vitamin D3 in addition to their background therapy. The active comparator group will receive vitamin D3 plus background therapy. Background therapy includes metformin, with insulin permitted and adjusted per investigator's judgment. Follow-up clinic visits are scheduled at Weeks 12, 26, 38, and 52. Efficacy will be assessed through MMTT-derived C-peptide and glucose measurements, as well as other glycemic indices. Safety will be monitored through the recording of adverse events, laboratory tests, and vital signs throughout the 52-week treatment period.

Вмешательства

• Препарат Cofrogliptin
  5 mg/tablet, oral; 2 tablets (10 mg) once every 2 weeks. Administered from randomization through Week 52.
• Препарат Vitamin D3
  400 IU/capsule, oral; 5 capsules (2000 IU) once daily. Administered from randomization through Week 52.
• Препарат Metformin
  Background therapy. Oral; typical daily dose 1.5 g, adjustable from 1.0 to 1.7 g/day per investigator judgment.
• Препарат Insulin
  Background therapy, as needed. Subcutaneous; individualized daily dose per investigator judgment.

Первичные конечные точки

• Change From Baseline in 2-hour Mixed-Meal Tolerance Test (MMTT) C-peptide Area Under the Curve (AUC) [Срок оценки: Baseline, Week 52]

Вторичные конечные точки (12)

• Change From Baseline in 2-hour MMTT C-peptide AUC at Weeks 12, 26, and 38 [Срок оценки: Baseline, Week 12, Week 26, Week 38]
• Change From Baseline in Fasting C-peptide (FCP) [Срок оценки: Baseline, Week 12, Week 26, Week 38, Week 52]
• Change From Baseline in 60-Minute Post-Meal C-peptide [Срок оценки: Baseline, Week 12, Week 26, Week 38, Week 52]
• Change From Baseline in 120-Minute Post-Meal C-peptide [Срок оценки: Baseline, Week 12, Week 26, Week 38, Week 52]
• Change From Baseline in Glycated Hemoglobin (HbA1c) [Срок оценки: Baseline, Week 26, Week 52]
• Proportion of Participants Achieving HbA1c < 7.0% [Срок оценки: Week 12, Week 26, Week 38, Week 52]
• Change From Baseline in Mean Daily Insulin Dose [Срок оценки: Baseline, Week 12, Week 26, Week 38, Week 52]
• Change From Baseline in Homeostatic Model Assessment of β-cell function (HOMA-β) [Срок оценки: Baseline, Week 12, Week 26, Week 38, Week 52]
• Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) [Срок оценки: Baseline, Week 12, Week 26, Week 38, Week 52]
• Change From Baseline in Glutamic Acid Decarboxylase Autoantibody (GADA) Titers [Срок оценки: Baseline, Week 52]
• Change From Baseline in Insulinoma-Associated Antigen-2 Autoantibody (IA-2A) Titers [Срок оценки: Baseline, Week 52]
• Change From Baseline in Zinc Transporter 8 Autoantibody (ZnT8A) Titers [Срок оценки: Baseline, Week 52]

Критерии участия

Критерии включения

• 1\. Voluntarily signed informed consent.
• 2\. Age 18 to 70 years, inclusive.
• 3\. Diagnosed with LADA, defined as meeting all of the following:
• (1) Meets 1999 WHO criteria for diabetes mellitus.
• (2) Age at diagnosis of diabetes ≥ 18 years.
• (3) Positive for at least one islet autoantibody (GADA, IA-2A, or ZnT8A).
• (4) Did not require continuous insulin therapy for at least 6 months after diagnosis.
• 4\. Stimulated C-peptide ≥ 200 pmol/L.
• 5\. Glycated Hemoglobin (HbA1c) ≤ 9.0%.
• 6\. For women of childbearing potential, must agree to use a highly effective method of contraception throughout the study.

Критерии исключения

• 1\. Pregnant, breastfeeding, or planning to become pregnant during the study.
• 2\. Gestational diabetes or other specific types of diabetes.
• 3\. Known hypersensitivity to Cogliptin, Vitamin D3, or their excipients.
• 4\. Use of DPP-4 inhibitors, GLP-1 receptor agonists, or thiazolidinediones (TZDs) within 8 weeks prior to randomization.
• 5\. Hypercalcemia (serum calcium above the upper limit of the normal range).
• 6\. Systemic corticosteroid therapy (oral or IV) for more than 7 consecutive days within 6 months prior to screening.
• 7\. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 times the upper limit of normal (ULN), or total bilirubin > 2 times ULN.
• 8\. Estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m².
• 9\. History of acute diabetic complications such as diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic state.
• 10\. History of pancreatitis or pancreatic surgery.
• 11\. New York Heart Association (NYHA) class III or IV congestive heart failure, or known left ventricular ejection fraction (LVEF) < 40%.
• 12\. History of malignancy.
• 13\. Severe psychiatric illness.
• 14\. History of alcohol or illicit drug dependence.
• 15\. Any other severe systemic disease that the investigator deems unsuitable for enrollment.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• The Second Xiangya Hospital, Central South University — Чанша

Идентификаторы

NCT: NCT07460336 · KOLA Study

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗