Evaluation of MTX-439 in Healthy Adults and Adults With Diabetic Kidney Disease

NCT07473323 | Recruiting Phase 1

• 1 other identifier: MTX-439-K101
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 1 randomized, double-blind, single ascending dose (SAD) and multiple ascending dose (MAD) study to assess the safety, tolerability, and Pharmacokinetics (PK) of single and multiple ascending doses of MTX-439 administered in healthy adults and adults with diabetic kidney disease (DKD)

Conditions

Healthy Adult Participants; Diabetic Kidney Disease

Keywords

MTX-439-K101; MTX-439; Healthy Volunteers; Diabetic Kidney Disease; HV; DKD; Adult; Monoclonal Antibody; SMOC2; SAD; MAD

Outcome Measures

Primary Outcomes (15)

• Incidence of Dose-Limiting Toxicities (DLTs)

  Number and percentage of participants who experience a dose-limiting toxicity (DLT) as defined in the protocol. Unit of Measure: Number of participants; Percentage of participants (%)

  From first dose up to Day 85 for SAD cohorts and up to Day 113 for MAD cohorts

• Incidence of Treatment-Emergent Adverse Events (TEAEs)

  Number and percentage of participants with at least one treatment-emergent adverse event (TEAE). TEAEs will be summarized by seriousness and maximum severity according to protocol-defined criteria Unit of Measure: Number of participants; Percentage of participants (%)

  From first dose up to Day 85 for SAD cohorts and up to Day 113 for MAD cohorts

• Incidence of Treatment-Related Adverse Events (TRAEs)

  Number and percentage of participants with at least one adverse event considered related to study intervention by the investigator. Unit of Measure: Number of participants; Percentage of participants (%)

  From first dose up to Day 85 for SAD cohorts and up to Day 113 for MAD cohorts

• Incidence of Dose Modifications Due to Adverse Events

  Number and percentage of participants requiring dose interruption, dose reduction, or permanent discontinuation of study intervention due to adverse events. Unit of Measure: Number of participants; Percentage of participants (%)

  From first dose up to Day 85 for SAD cohorts and up to Day 113 for MAD cohorts

• Clinically Significant Changes in Physical Examination Findings

  Number and percentage of participants with clinically significant abnormalities in physical examination findings. Unit of Measure: Number of participants; Percentage of participants (%)

  Baseline up to Day 85 for SAD cohorts and up to Day 113 for MAD cohorts

• Clinically Significant Changes in Vital Signs

  Number and percentage of participants with clinically significant changes from baseline in vital signs measurements (including blood pressure, heart rate, respiratory rate, temperature, and pulse oximetry). Unit of Measure: Number of participants; Percentage of participants (%)

  Baseline up to Day 85 for SAD cohorts and up to Day 113 for MAD cohorts

• Clinically Significant Changes in Electrocardiogram (ECG) Parameters

  Number and percentage of participants with clinically significant abnormalities in ECG parameters (including but not limited to PR interval, QRS duration, and QT/QTc interval). Unit of Measure: Number of participants; Percentage of participants (%)

  Baseline up to Day 85 for SAD cohorts and up to Day 113 for MAD cohorts

• Clinically Significant Changes in Clinical Laboratory Parameters

  Number and percentage of participants with clinically significant changes from baseline in hematology, clinical chemistry, urinalysis, and other protocol-specified laboratory parameters. Unit of Measure: Number of participants; Percentage of participants (%)

  Baseline up to Day 85 for SAD cohorts and up to Day 113 for MAD cohorts

• Maximum Observed Plasma Concentration (Cmax) of MTX-439

  Maximum observed plasma concentration (Cmax) of MTX-439 following single and multiple ascending doses. Unit of Measure: Nanograms per milliliter (ng/mL)

  From first dose up to Day 85 for SAD cohorts and up to Day 113 for MAD cohorts

• Area Under the Plasma Concentration-Time Curve From Time Zero to Time t (AUC0-t) of MTX-439

  Area under the plasma concentration-time curve from time zero to the last measurable concentration (AUC0-t) of MTX-439. Unit of Measure: Nanogram·hour per milliliter (ng·h/mL)

  From first dose up to Day 85 for SAD cohorts and up to Day 113 for MAD cohorts

• Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of MTX-439

  Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC0-∞) of MTX-439. Unit of Measure: Nanogram·hour per milliliter (ng·h/mL)

  From first dose up to Day 85 for SAD cohorts and up to Day 113 for MAD cohorts

• Area Under the Plasma Concentration-Time Curve Over the Dosing Interval (AUC0-tau) of MTX-439

  Area under the plasma concentration-time curve over the dosing interval (AUC0-tau) of MTX-439 at steady state, where applicable Unit of Measure: Nanogram·hour per milliliter (ng·h/mL)

  From first dose up to Day 85 for SAD cohorts and up to Day 113 for MAD cohorts

• Time to Maximum Plasma Concentration (Tmax) of MTX-439

  Time to reach maximum observed plasma concentration (Tmax) of MTX-439 following dosing. Unit of Measure: Hours (h)

  From first dose up to Day 85 for SAD cohorts and up to Day 113 for MAD cohorts

• Terminal Elimination Half-Life (t1/2) of MTX-439

  Terminal elimination half-life (t1/2) of MTX-439 following dosing. Unit of Measure: Hours (h)

  From first dose up to Day 85 for SAD cohorts and up to Day 113 for MAD cohorts

• Incidence and Characterization of Anti-Drug Antibodies (ADA)

  Number and percentage of participants with detectable anti-drug antibodies (ADA), including ADA titer and assessment of the impact of ADA on PK and safety, if applicable. Unit of Measure: Number of participants; Percentage of participants (%); Titer (unitless dilution factor)

  From first dose up to Day 85 for SAD cohorts and up to Day 113 for MAD cohorts

Secondary Outcomes (2)

• Change From Baseline in Total SMOC2 Levels

  Baseline up to Day 85 for SAD cohorts and up to Day 113 for MAD cohorts

• Change From Baseline in Free SMOC2 Levels

  Baseline up to Day 85 for SAD cohorts and up to Day 113 for MAD cohorts

Other Outcomes (2)

• Change From Baseline in Pro-inflammatory Biomarkers

  Baseline up to Day 85 for SAD cohorts and up to Day 113 for MAD cohorts

• Change From Baseline in Fibrosis Biomarkers

  Baseline up to Day 85 for SAD cohorts and up to Day 113 for MAD cohorts

Study Arms (2)

MTX-439

EXPERIMENTAL

MTX-439

Biological: MTX-439

Placebo

PLACEBO COMPARATOR

Placebo

Other: Placebo

Interventions

MTX-439 BIOLOGICAL

MTX-439 is a recombinant human immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that binds human-secreted protein SMOC2 with high specificity and high affinity

MTX-439

Placebo OTHER

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All genders, ages 18 to 65 years, inclusive.
• Able to read and understand the study and all related materials (including the ICF), and provide a signed, written informed consent.
• Willing and able to complete all protocol-required study visits and procedures.
• Consumption of no more than 5 cigarettes or other cotinine-containing products (including tobacco, nicotine gum, patches, nicotine pouches, and e-cigarettes) per week and agreement to abstain from all such products during inpatient stays.
• Willing to refrain from marijuana- or cannabinol-containing products for 30 days before Screening and until the last study visit.
• Agrees to not donate eggs (if applicable) from the time of the first infusion until 65 days after the final dose, or 125 days after the final dose for sperm (if applicable); additionally agrees to not donate blood from 56 days prior to the time of first infusion until 90 days after the last study visit or platelets/plasma from 14 days prior to the time of first infusion until 90 days after the last study visit.
• Participants are required to follow specific contraception measures as follows:
• Participants assigned male at birth must use a condom (even if vasectomised) at the time of Screening and for 125 days after the final dose.
• Participants assigned female at birth must be of nonchildbearing potential (defined as either at least 6 months surgically sterilised or at least 1 year postmenopausal and confirmed by follicle-stimulating hormone \[FSH\] level \> 40 U/L) OR, if of childbearing potential (defined as not sterilised via bilateral oophorectomy or hysterectomy; still menstruating; or \< 1 year has passed since the last menses, if menopausal), must use a combination of 1 highly effective method of contraception and 1 effective method of contraception. This contraceptive practice should begin at least 28 days before the first dose of study drug, continue during the study, and persist for 65 days after the final dose of study drug, if applicable.
• Male participants agree to ensure that their female partners who are of childbearing potential will use a highly effective method of contraception..
• Vital signs within the following ranges:
• Systolic blood pressure: 90-140 mmHg
• Diastolic blood pressure: \< 90 mmHg
• Pulse rate: 55-100 bpm
• Respiration rate: 10-16 respirations per minute

You may not qualify if:

• Any active medical condition determined clinically significant by the Investigator, except for DKD (for DKD participants).
• Body mass index (BMI) \> 32 kg/m2 for healthy participants; \> 40 kg/m2 for DKD participants.
• Use of any systemic immunosuppressant medications, medications to treat diabetes (except DKD participants), antipsychotics, anticoagulants, or other prescription medications other than contraceptives within 90 days of Screening that, as determined by the Investigator, could confound their participation in the study.
• Received a vaccine within 30 days of Screening.
• Cancer or a history of cancer or lymphoproliferative disorder within 5 years of Screening except for adequately treated non-melanoma cancers of the skin and cervical carcinoma in situ.
• Currently pregnant, lactating, or planning to conceive or contribute to pregnancy during the trial and up to 65 days (for participants 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, as determined by the Investigator, 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 at Screening or admission to the CRU (Day -1).
• Donation of blood within 28 days of Screening.
• Any clinically significant disease or laboratory abnormality detected at Screening, including diabetes mellitus, that might interfere with a participant's ability to complete the study, on-study evaluations, or participant safety, including the following:
• Haemoglobin \< 115 g/L (female) or \< 135 g/L (male); \> 160 g/L (female) or \> 180 g/L (male)
• Absolute neutrophils \< 2.0 × 109/L or \> 7.5 × 109/L
• White blood cells \< 4.0 × 109/L or \> 11.0 × 109/L

Sponsors & Collaborators

• Mediar Therapeutics: lead

Study Sites (1)

Doherty Clinical Trials

Melbourne, Victoria, 3002, Australia

RECRUITING

MeSH Terms

Conditions

Diabetic Nephropathies

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Central Study Contacts

Jeffrey Bornstein, MD

CONTACT

(617) 936-0960; jeffrey@mediartx.com

Jordan Jara

CONTACT

617-936-0960; jordan.jara@mediartx.com

Study Design

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

Study Record Dates

• First Submitted: February 26, 2026
• First Posted: March 16, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): January 1, 2028
• Last Updated: May 20, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)