MTX-439: MTX-439 is a recombinant human immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that binds human-secreted protein SMOC2 with high specificity and high affinity
Placebo: Placebo
Study 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)
Eligibility
Sex
ALL
Min age
18 Years
Max age
65 Years
Healthy volunteers
Accepted
Inclusion Criteria:
1. All genders, ages 18 to 65 years, inclusive.
2. Able to read and understand the study and all related materials (including the ICF), and provide a signed, written informed consent.
3. Willing and able to complete all protocol-required study visits and procedures.
4. 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.
5. Willing to refrain from marijuana- or cannabinol-containing products for 30 days before Screening and until the last study visit.
6. 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.
7. 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..
8. 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
DKD participants:
9. All of the above.
* Well-controlled diabetes requiring minimal dose adjustments of antidiabetic medications in the past 3 months and no adjustments within 30 days of Screening.
* Haemoglobin A1C \< 9.5%.
* Estimated glomerular filtration rate (eGFR) between 30 and 60.
Exclusion Criteria:
1. Any active medical condition determined clinically significant by the Investigator, except for DKD (for DKD participants).
2. Body mass index (BMI) \> 32 kg/m2 for healthy participants; \> 40 kg/m2 for DKD participants.
3. 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.
4. Received a vaccine within 30 days of Screening.
5. 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.
6. Current infection with hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) as evidenced by a positive hepatitis B surface antigen (HbsAg) test at Screening or a positive HIV test at Screening. For hepatitis C, a positive hepatitis C antibody (antiHCV) test is exclusionary unless the participant has previously been treated for hepatitis C, in which case they would be eligible with a negative HCV ribonucleic (RNA) test.
7. 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.
8. History of severe depression, psychosis, or suicidal ideation, as determined by the Investigator, within 5 years of Screening.
9. History of anaphylaxis or other significant allergies in the opinion of the Investigator.
10. History of substance use disorder as specified in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, within 1 year of Screening.
11. Positive screen for drugs of abuse or alcohol at Screening or admission to the CRU (Day -1).
12. Donation of blood within 28 days of Screening.
13. 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
* Platelet count \< 150 × 109/L or \> 450 × 109/L
* Any clinically significant abnormality on any of the Screening ECGs
* Alanine aminotransferase or aspartate aminotransferase greater than 1.2 times the upper limit of normal.
14. Any surgical procedure, including planned procedures within 12 weeks of Screening.
15. Known allergy to MTX-439 or any of its excipients.
16. Participation in another research study of an investigational agent within 30 days of Screening or 5 half-lives of the agent, whichever is longer.
Primary outcome measure(s)
Incidence of Dose-Limiting Toxicities (DLTs) — From first dose up to Day 85 for SAD cohorts and up to Day 113 for MAD cohorts 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 (%)
Incidence of Treatment-Emergent Adverse Events (TEAEs) — From first dose up to Day 85 for SAD cohorts and up to Day 113 for MAD cohorts 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 (%)
Incidence of Treatment-Related Adverse Events (TRAEs) — From first dose up to Day 85 for SAD cohorts and up to Day 113 for MAD cohorts 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 (%)
Incidence of Dose Modifications Due to Adverse Events — From first dose up to Day 85 for SAD cohorts and up to Day 113 for MAD cohorts 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 (%)
Clinically Significant Changes in Physical Examination Findings — Baseline up to Day 85 for SAD cohorts and up to Day 113 for MAD cohorts Number and percentage of participants with clinically significant abnormalities in physical examination findings.
Unit of Measure:
Number of participants; Percentage of participants (%)
Clinically Significant Changes in Vital Signs — Baseline up to Day 85 for SAD cohorts and up to Day 113 for MAD cohorts 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 (%)
Clinically Significant Changes in Electrocardiogram (ECG) Parameters — Baseline up to Day 85 for SAD cohorts and up to Day 113 for MAD cohorts 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 (%)
Clinically Significant Changes in Clinical Laboratory Parameters — Baseline up to Day 85 for SAD cohorts and up to Day 113 for MAD cohorts 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 (%)
Maximum Observed Plasma Concentration (Cmax) of MTX-439 — From first dose up to Day 85 for SAD cohorts and up to Day 113 for MAD cohorts Maximum observed plasma concentration (Cmax) of MTX-439 following single and multiple ascending doses.
Unit of Measure:
Nanograms per milliliter (ng/mL)
Area Under the Plasma Concentration-Time Curve From Time Zero to Time t (AUC0-t) of MTX-439 — 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 the last measurable concentration (AUC0-t) of MTX-439.
Unit of Measure:
Nanogram·hour per milliliter (ng·h/mL)
Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of MTX-439 — 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.
Unit of Measure:
Nanogram·hour per milliliter (ng·h/mL)
Area Under the Plasma Concentration-Time Curve Over the Dosing Interval (AUC0-tau) of MTX-439 — 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 at steady state, where applicable
Unit of Measure:
Nanogram·hour per milliliter (ng·h/mL)
Time to Maximum Plasma Concentration (Tmax) of MTX-439 — From first dose up to Day 85 for SAD cohorts and up to Day 113 for MAD cohorts Time to reach maximum observed plasma concentration (Tmax) of MTX-439 following dosing.
Unit of Measure:
Hours (h)
Terminal Elimination Half-Life (t1/2) of MTX-439 — 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 following dosing.
Unit of Measure:
Hours (h)
Incidence and Characterization of Anti-Drug Antibodies (ADA) — From first dose up to Day 85 for SAD cohorts and up to Day 113 for MAD cohorts 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)
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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