A First-in-Human Safety Trial of MTX-474

NCT06535841 | Completed Phase 1

• 1 other identifier: MTX-474-S101
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Healthy

Keywords

MTX-474-S101; MTX-474; Healthy Volunteer; MAD; SAD; Adult; Healthy

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (1)

• Blood serum samples will be collected to assess the target engagement of MTX-474 in healthy adult participants

  Through Day 29 (SAD Cohort) or Day 50 (MAD Cohort)

Other Outcomes (13)

• To assess the effect of MTX-474 on PD biomarker PRO-C3 for fibrosis in healthy adult participants

  Through Day 50 (MAD Cohort)

• To assess the effect of MTX-474 on PD biomarker PRO-C6 for fibrosis in healthy adult participants

  Through Day 50 (MAD Cohort)

• To assess the effect of MTX-474 on PD biomarker C7M for fibrosis in healthy adult participants

  Through Day 50 (MAD Cohort)

Study Arms (2)

MTX-474

EXPERIMENTAL

Biological: MTX-474

Biological: MTX-474

Placebo

PLACEBO COMPARATOR

Placebo

Other: Placebo

Interventions

MTX-474 BIOLOGICAL

MTX-474 is an immunoglobin G1 (IgG1) monoclonal antibody directed against Ephrin B2 that binds to and has demonstrated ability to block phosphorylation of its preferred receptor EphB4. Increased levels of circulating soluble EphrinB2 have been found in patients with systemic sclerosis.

MTX-474

Placebo OTHER

Matching Placebo - Normal Saline

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• All genders, ages 18 to 60 years, inclusive
• Willing and able to complete all protocol-required study visits and procedures
• Consumption of not more than 5 cigarettes or other cotinine-containing products (including tobacco, nicotine gum, patches, and e-cigarettes) per week as long as they are willing to abstain nicotine use approximately 5 days prior to admission and during inpatient stays
• Willing to refrain from marijuana- or cannabinol-containing products for 30 days before Screening and until the last study visit
• Agree to a highly effective method of contraception for 28 days prior to the first dose of study drug, and persist through 65 days after the last dose of study drug.

You may not qualify if:

• Any concurrent active medical condition determined clinically significant by the Investigator
• Body mass index (BMI) \>32 kg/m2 or body weight \>100kg
• Use of any systemic immunosuppressant medications, medications to treat diabetes, antipsychotics, anticoagulants, or other medications within 90 days of Screening
• Cancer or a history of cancer or lymphoproliferative disorder within 5 years of Screening other than adequately treated non-melanomatous skin cancers or cervical carcinoma in situ
• Current infection with hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) as evidenced by a positive hepatitis B surface antigen or a positive HIV test at Screening
• Currently pregnant, lactating, or planning to conceive or contribute to pregnancy during the trial and up to 65 days (for women of childbearing potential) or 125 days (for males) after the participant's last dose of study drug, if applicable
• History of severe depression, psychosis, or suicidal ideation within 5 years of Screening
• History of anaphylaxis or other significant allergies in the opinion of the Investigator
• History of substance use disorder as specified in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, within 1 year of Screening
• Positive screen for drugs of abuse or alcohol intake at Screening or admission to the CRU (Day -1)
• Any clinically significant disease or laboratory abnormality detected at Screening that might interfere with a participant's ability to complete the study, on-study evaluations, or participant safety
• Any surgical procedure, including planned procedures within 12 weeks of Screening
• Participation in another research study of an investigational agent within 30 days of Screening or 5 half-lives of the agent, whichever is longer.

Sponsors & Collaborators

• Mediar Therapeutics: lead

Study Sites (1)

Nucleus Network

Herston, Queensland, 4006, Australia

Location

Study Officials

• Jeffrey Bornstein, MD

  Mediar Therapeutics

  STUDY DIRECTOR

• Gloria Wong, PhD, MBBS

  Nucleus Network Brisbane

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2024
• First Posted: August 2, 2024
• Study Start: July 10, 2024
• Primary Completion: April 24, 2025
• Study Completion: April 24, 2025
• Last Updated: May 18, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)