An Adaptive Design Study of MTX228
NCT Number: NCT06474598
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Type 1 Diabetes Mellitus
Interventions: DRUG: MTX228|DEVICE: DEXCOM G6
Sponsor: University of Alberta
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 24
Study Design: Allocation: NON_RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-08
Completion Date: 2027-12

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.

Primary Outcome Measures: 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 Outcome Measures: Lowered or increased total daily insulin dose, Changes in total daily insulin dose will be monitored as per:

•Change in daily insulin use as recorded in subject's journal

To observe if an increase in MTX228 will decrease daily insulin usage, Days 84 and 168|To assess the time spent in a plasma glucose range of 3.9-10.0 mol/L, Changes in total daily insulin dose will be monitored based upon continuous glucose monitoring (CGM) Which dose of MTX228 helps facilitate a longer period of time spent in this optimal plasma glucose range, 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, Changes in total daily insulin dose will be monitored based on continuous glucose monitoring (CGM)

Assessing which dose of MTX228 is least effective at keeping the participant out of the high and very high range. This will help aide in the dose selection phase, Days 84 and 168|Change in HbA1c, Changes in total daily insulin dose will be monitored as per CGM and blood tests.

Ideally, HbA1c should be lowered over time with an increased dose of MTX228, Days 84 and 168|Change in fasting plasma glucose (FPG), If the beneficial metabolic effects are mediated by an expansion of beta cell mass they should persist during the washout period., Days 84 and 168|The number of episodes of level 2 and 3 hypoglycemia in study participants, The number and duration of level 2 and 3 hypoglycemic events based upon CGM throughout treatment and follow up. Ideal doses of MTX228 should decrease the number of episodes for participants., Days 84 and 168
Other Outcome Measures: Changes in AUC C-peptide between days 0 and 168, and between Days 84 and 168 in those completing the optional extension study., •Changes observed in C-peptide or metabolic responses which increase during the extension period would support a longer treatment duration., 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), •Early onset type 1 diabetes is associated with a more rapid decline in beta cell mass, days 0 and 168, and between Days 84 and 168|•Stratified analysis by baseline C-peptide level, diabetes duration, age of diabetes onset, HbA1c, The potential for beta cell regeneration may be dependent on how many beta cells are present and current metabolic demands, days 0 and 168, and between Days 84 and 168