A First-in-Human Safety Trial of MTX-463

Mediar Therapeutics

Status and phase

Completed

Phase 1

Conditions

Healthy

Treatments

Biological: MTX-463

Other: Placebo

Study type

Interventional

Funder types

Industry

Identifiers

NCT06401213

MTX-463-I101

Details and patient eligibility

About

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-463 administered in healthy adults.

Full description

This is 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-463 administered in healthy adults.

SAD Portion

The SAD portion of the study will consist of 4 planned dosing cohorts each comprising 8 healthy participants. The starting dose will be 4 mg/kg (Cohort 1) with subsequent planned doses of 8 mg/kg (Cohort 2), 16 mg/kg (Cohort 3), and 30 mg/kg (Cohort 4). Planned doses may be adjusted in response to the data. Additional participants and/or additional dosing cohorts may be added as needed based on the data.

Within each cohort, participants will be randomly assigned to receive MTX-463 or matched placebo. The first 2 participants (sentinel participants) within each cohort will be randomized 1:1 to receive MTX-463 or placebo on Day 1. These participants will be monitored for 24 hours, and after review of the safety data from both participants and approval by the study Investigator and Sponsor's responsible medical officer (SRMO), the additional 6 participants will be randomized to study drug (n=5 MTX-463; n=1 placebo).

Each participant will undergo assessments at specified timepoints on Days 1 through 60. End-of-Study (EOS) procedures will be completed on Day 28 or upon early termination (ET). An End-of-Follow-up (EOF) assessment of PK and ADA will be completed on Day 60.

MAD Portion

The MAD portion of the study will consist of 3 planned dosing cohorts. Each cohort will comprise 8 healthy participants (n=6 MTX-463; n=2 placebo). The starting dose will be a 6.6 mg/kg loading dose and 4 mg/kg maintenance doses (Cohort 1) with subsequent planned doses of a 13 mg/kg loading dose and 8 mg/kg maintenance doses (Cohort 2), and a 27 mg/kg loading dose and 16 mg/kg maintenance doses (Cohort 3). Planned doses may be adjusted in response to the data. Additional participants and/or additional dosing cohorts may be added as needed based on the data.

On Day 1, participants will be randomized to receive either MTX-463 or matched placebo. The randomized participants will receive a single loading dose on Day 1 followed by 2 maintenance doses of study drug on Day 8 and Day 22. Participants will be housed inpatient from Day -1 through post-dose observation on Day 8 and from Day 21 through assessments on Day 29. All other visits will be conducted in the outpatient setting. Each participant will undergo assessments at specified timepoints on Days 1 through 82. End-of-study procedures will be completed on Day 50, or upon ET. An EOF assessment of PK and ADA will be completed on Day 82.

Safety and tolerability of MTX-463 will be reviewed through Day 29 by the study Investigator and SRMO to inform dose escalation decisions for the next dose cohort.

Additional cohorts for the SAD and MAD portions of the study may be added as needed to potentially explore lower doses.

Enrollment

56 patients

Sex

All

Ages

18 to 60 years old

Volunteers

Accepts Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

All genders, ages 18 to 60 years, inclusive
Willing and able to complete all protocol-required study visits and procedures
Non-smoker and has not used nicotine- or cotinine-containing products (including tobacco, nicotine gum, patches, and e-cigarettes) for at least 90 days before Screening and until the last study visit
Willing to refrain from marijuana- or cannabinol-containing products for 90 days before Screening and until the last study visit
Willing to refrain from ingestion of alcohol from 7 days before Screening 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 28 days after the last dose of study drug

Key Exclusion Criteria:

- Any history of clinically significant lung disease as determined by the Investigator, including but not limited to asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, pulmonary embolus, or pulmonary arterial hypertension
Any other concurrent active medical condition determined clinically significant by the Investigator
Body mass index (BMI) >40 kg/m2
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 28 days 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 substance use disorder as specified in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, within 1 year of Screening
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