An Adaptive Design Study of MTX228

NCT06474598 | Recruiting Phase 2 DMC

• 1 other identifier: MTX228-2024
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

MTX228 has been identified as a medication that might allow the re-growth of insulin producing beta cells in people with Type 1 Diabetes. Promoting the re-growth of lost beta cells would be beneficial to people with Type 1 Diabetes because it would allow them to take less insulin by injection and would improve their overall blood sugar control while reducing the risk and rate of low blood sugars. This open-label dose selection study aims to determine the optimal dose ofMTX228 for use in a future phase IIb study. The purpose is to investigate the relative effectiveness of different doses of MTX228 and to select the most effective dose for further investigation in a phase 2b study.

Conditions

Type 1 Diabetes Mellitus

Outcome Measures

Primary Outcomes (2)

• Change in AUC C-peptide

  C-peptide level as it relates to MTX228 doses Change in postprandial C-peptide level area under the curve (AUC), in a 2-hour Mixed Meal Tolerance Test (MMTT), between Days 0 and 84, as well as a change in AUC C-peptide between subjects receiving different doses of MTX228. Justification being that the ideal dose of MTX228 will cause the largest relative increase in C-peptide levels.

  Days 0 and 84

• Dose selection for phase IIb study

  A change in AUC C-peptide between subjects receiving different doses of MTX228 will determine the best doses Justification being that the ideal dose of MTX228 will cause the largest relative increase in C-peptide levels.

  Days 0 and 84

Secondary Outcomes (6)

• Lowered or increased total daily insulin dose

  Days 84 and 168

• To assess the time spent in a plasma glucose range of 3.9-10.0 mol/L

  Days 84 and 168

• Time spent in high range (10.1-13.9 mmol/L) and very high range (>13.9) based upon CGM in the last two weeks of the main treatment period and separately of the extended treatment

  Days 84 and 168

• Change in HbA1c

  Days 84 and 168

• Change in fasting plasma glucose (FPG)

  Days 84 and 168

Other Outcomes (3)

• Changes in AUC C-peptide between days 0 and 168, and between Days 84 and 168 in those completing the optional extension study.

  days 0 and 168, and between Days 84 and 168

• •Changes in secondary end-points between days 0 and 168, and between Days 84 and 168 (in subjects completing the extension study)

  days 0 and 168, and between Days 84 and 168

• •Stratified analysis by baseline C-peptide level, diabetes duration, age of diabetes onset, HbA1c

  days 0 and 168, and between Days 84 and 168

Study Arms (3)

100 mg QD

ACTIVE COMPARATOR

Participants will be assigned to receive 3 months oral tablet administration of MTX228 at the 100mg QD dose

Drug: MTX228; Device: DEXCOM G6

100 mg BID

ACTIVE COMPARATOR

Participants will be assigned to receive 3 months oral tablet administration of MTX228 at the 100mg BID dose

Drug: MTX228; Device: DEXCOM G6

200 mg QD

ACTIVE COMPARATOR

Participants will be assigned to receive 3 months oral tablet administration of MTX228 at the 200mg BID dose

Drug: MTX228; Device: DEXCOM G6

Interventions

MTX228 DRUG

Tolimidone was developed as a treatment for gastric ulcers but did not advance beyond phase 2 clinical trials because of lack of efficacy. Subsequently, tolimidone has been identified as an activator of Lyn kinase and was considered as a treatment for type 2 diabetes as an insulin sensitizer because of Lyn's interaction with insulin signaling molecules. More recently, Lyn has been identified as a critical regulator of beta-cell mass, with genetic and biochemical inactivation of Lyn provoking beta-cell death in isolated human islets and precipitated diabetes in mice, and activation of Lyn stimulating beta-cell survival and beta-cell proliferation. These findings strongly suggest that small molecule activators of Lyn, such as Tolimidone, could represent new therapeutic options to promote beta-cell regeneration in type 1 diabete

Also known as: Tolimidone

100 mg BID; 100 mg QD; 200 mg QD

DEXCOM G6 DEVICE

To monitor participants blood glucose levels continuously

100 mg BID; 100 mg QD; 200 mg QD

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• clinical diagnosis of T1DM with onset before the age of 35 requiring continuous treatment with insulin within 1 year of diagnosis and the presence of positive T1DM autoantibody titer if diagnosed after age 35 (past or present
• HbA1c between 6.0 - 10.0 %.
• Willing to wear study-provided CGM and share CGM data via cloud.
• Diagnosis of T1DM ≥1year at time of screening.
• Fasting or random (post-prandial) C-peptide level ≥ 100 pmol/l (or 0.3 ng/mL) during screening or pre-screening. Pre-screening C-peptide levels may be obtained by the study team (subject to patient's written consent) up to 56 days before planned enrolment to reduce the number of screen failures.
• BMI ≤ 35 kg/m2
• eGFR \>45 ml/min/1.73m2
• Able and willing to comply with the study protocol for the duration of the study
• Written informed consent must be obtained before any study-related assessment is performed.

You may not qualify if:

• Diagnosis or history indicative of monogenic, Type 2 or post-pancreatectomy diabetes
• History of \>1 episode of severe (level 3) hypoglycemia in the prior 6 months
• Significant cardiovascular history defined as:
• History of myocardial infarction, coronary angioplasty or bypass grafts, valvular disease or repair, unstable angina pectoris, transient ischemic attack, or cerebrovascular accidents within six months prior to entry into the study
• Congestive heart failure defined as New York Heart Association (NYHA) stage III and IV
• Uncontrolled hypertension defined as SBP \> 160 mmHg and/or DBP \> 100 mmHg
• Symptomatic postural hypotension
• Use of systemic corticosteroids (except physiologic replacement doses for adrenal insufficiency) or other medications that would influence insulin sensitivity
• Use of non-insulin antihyperglycemic agents within prior 30 days.
• History of significant other major or unstable neurological, metabolic, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, or urological disorder including previous solid organ or cell transplant that would impact patient safety or data interpretation.
• History of cancer, other than squamous cell or basal cell carcinoma of the skin, that has not been in full remission for at least 5 years before screening (any history of treated cervical intraepithelial neoplasia is allowed)
• Known recreational substance use or psychiatric illness that, in the opinion of the Investigator, may impact the safety of the subject or objectives with scheduled visits
• A history of alcohol or drug abuse or drug addiction in the previous 12 months
• A positive pregnancy blood test for women of childbearing age or breast-feeding women 12 Are unwilling to use an "effective" method of contraception during the course of the study. Sexually active male patients, who could have children, are required to use a condom or abstained from intercourse, and refrain from sperm donation for the purposes of conception. Females have to be surgically sterile (via hysterectomy or bilateral tubal ligation) or post-menopausal or using a medically acceptable barrier method of contraception (i.e. IUD, barrier methods with spermicide or abstinence).

Sponsors & Collaborators

• University of Alberta: lead

Study Sites (1)

University of Alberta

Edmonton, Alberta, T6G 2R3, Canada

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Central Study Contacts

Dominique Forrest

CONTACT

7802481770; dforres1@ualberta.ca

Peter Senior

CONTACT

psenior@ualberta.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2024
• First Posted: June 25, 2024
• Study Start: November 14, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: April 13, 2026

Record last verified: 2026-04

Locations

CA (1)