A First-in-Human Safety Trial of MTX-474
NCT Number: NCT06535841
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1
Conditions: Healthy
Interventions: BIOLOGICAL: MTX-474|OTHER: Placebo
Sponsor: Mediar Therapeutics
Collaborators: ProPharma Group
Sex: ALL
Age: ADULT
Enrollment: 80
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: TRIPLE (PARTICIPANT, CARE_PROVIDER, INVESTIGATOR)|Primary Purpose: OTHER
Start Date: 2024-07-10
Completion Date: 2025-05-28
Locations: Nucleus Network, Herston, Queensland, 4006, Australia

Summary:
A randomized, double-blind, placebo-controlled, single ascending dose (SAD) and multiple ascending dose (MAD) study to assess the safety, tolerability, and PK of single and multiple ascending doses of MTX-474 administered in healthy adults.

Primary Outcome Measures: Incidence of Treatment-Related Adverse Events in healthy volunteers, Clinical Safety Labs are collected, and Adverse Events are assessed in both inpatient and outpatient clinic visits, Through Day 29 (SAD Cohort) or Day 50 (MAD Cohort)|MTX-474 PK by dose will be evaluated for Cmax, as feasible, Blood serum samples will be collected at protocol-specified timepoints throughout the study, Through Day 29 (SAD Cohort) or Day 50 (MAD Cohort)|Serum sample results will be summarized for presence of Anti-Drug Antibodies during the SAD and MAD portions of the study, Blood serum samples will be collected at protocol-specified timepoints throughout the study to assess for the presence and titer (if applicable) of Anti-Drug Antibodies., Through Day 29 (SAD Cohort) or Day 50 (MAD Cohort)|MTX-474 PK by dose will be evaluated for AUC0-t, as feasible, Blood serum samples will be collected at protocol-specified timepoints throughout the study, Through Day 29 (SAD Cohort) or Day 50 (MAD Cohort)|MTX-474 PK by dose will be evaluated for AUC0-tau (MAD only), as feasible, Blood serum samples will be collected at protocol-specified timepoints throughout the study, Through Day 29 (SAD Cohort) or Day 50 (MAD Cohort)|MTX-474 PK by dose will be evaluated for AUC0-∞, as feasible, Blood serum samples will be collected at protocol-specified timepoints throughout the study, Through Day 29 (SAD Cohort) or Day 50 (MAD Cohort)
Secondary Outcome Measures: Blood serum samples will be collected to assess the target engagement of MTX-474 in healthy adult participants, These assessments will be summarized as:

Change from Baseline in bound EphrinB2 levels Change from Baseline in free EphrinB2 levels Change from Baseline in the percent phorphoEphB4 (pEpB4) positive cells and ratio of pEpB4 to total EphB4 positive cells, Through Day 29 (SAD Cohort) or Day 50 (MAD Cohort)
Other Outcome Measures: To assess the effect of MTX-474 on PD biomarker PRO-C3 for fibrosis in healthy adult participants, Change from Baseline in fibrosis biomarker PRO-C3 will be evaluated., Through Day 50 (MAD Cohort)|To assess the effect of MTX-474 on PD biomarker PRO-C6 for fibrosis in healthy adult participants, Change from Baseline in fibrosis biomarker PRO-C6 will be evaluated., Through Day 50 (MAD Cohort)|To assess the effect of MTX-474 on PD biomarker C7M for fibrosis in healthy adult participants, Change from Baseline in fibrosis biomarker C7M will be evaluated., Through Day 50 (MAD Cohort)|To assess the effect of MTX-474 on PD biomarker PRO-C4 for fibrosis in healthy adult participants, Change from Baseline in fibrosis biomarker PRO-C4 will be evaluated., Through Day 50 (MAD Cohort)|To assess the effect of MTX-474 on PD biomarker IFN-γ for inflammation in healthy adult participants, Change from Baseline in pro-inflammatory biomarker IFN-γ will be evaluated., Through Day 50 (MAD Cohort)|To assess the effect of MTX-474 on PD biomarker IL-1β for inflammation in healthy adult participants, Change from Baseline in pro-inflammatory biomarker IL-1β will be evaluated., Through Day 50 (MAD Cohort)|To assess the effect of MTX-474 on PD biomarker IL-2 for inflammation in healthy adult participants, Change from Baseline in pro-inflammatory biomarker IL-2 will be evaluated., Through Day 50 (MAD Cohort)|To assess the effect of MTX-474 on PD biomarker IL-4 for inflammation in healthy adult participants, Change from Baseline in pro-inflammatory biomarker IL-4 will be evaluated., Through Day 50 (MAD Cohort)|To assess the effect of MTX-474 on PD biomarker IL-6 for inflammation in healthy adult participants, Change from Baseline in pro-inflammatory biomarker IL-6 will be evaluated., Through Day 50 (MAD Cohort)|To assess the effect of MTX-474 on PD biomarker IL-10 for inflammation in healthy adult participants, Change from Baseline in pro-inflammatory biomarker IL-10 will be evaluated., Through Day 50 (MAD Cohort)|To assess the effect of MTX-474 on PD biomarker IL-12p70 for inflammation in healthy adult participants, Change from Baseline in pro-inflammatory biomarker IL-12p70 will be evaluated., Through Day 50 (MAD Cohort)|To assess the effect of MTX-474 on PD biomarker IL-17A for inflammation in healthy adult participants, Change from Baseline in pro-inflammatory biomarker IL-17A will be evaluated., Through Day 50 (MAD Cohort)|To assess the effect of MTX-474 on PD biomarker TNF-α for inflammation in healthy adult participants, Change from Baseline in pro-inflammatory biomarker TNF-α will be evaluated., Through Day 50 (MAD Cohort)