Evaluation of MTX-463 Administered Subcutaneously in Healthy Adult Males
MTX-463-I102: A Phase 1 Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety, Tolerability, and Pharmacokinetics of MTX-463 Administered Subcutaneously in Healthy Adult Males
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This is a randomized, double-blind, placebo-controlled, study to assess the safety, tolerability, and PK of MTX-463 when administered via SC injection in healthy adult males. The study will consist of a single cohort comprising 8 healthy male participants, who on Day 1 will be randomly assigned to receive MTX-463 or matched placebo. Randomization will be in a 3:1 ratio such that 6 participants will receive MTX-463 and 2 will receive placebo. Participants randomized to MTX-463 will receive a dose of 250 mg of MTX-463.
Participants randomized to placebo will receive SC injections containing sodium chloride 0.9%. The injections will be given under the skin of the abdominal wall on Day 1. Blood will be drawn pre-dose on Day 1 for PK and antidrug antibodies (ADAs) and post-dose for PK at 6 and 24 hours. Participants will remain in the clinical research unit (CRU) for 24 hours after their injections, and then they will return for outpatient PK blood draws on Days 3 through 8, 15, and 22, with blood drawn for ADA assessment on Days 15 and 22. Each participant will undergo assessments at specified timepoints on Days 1 through 22 as detailed in Table 1. End-of-study procedures will be completed on Day 22 or upon early termination (ET). Local safety and tolerability at the injection site will be assessed at the time of the injections and for 24 hours afterward, and on Days 5, 8, 15 (±1 day), and 22 (±2 days) (EOS/ET).
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Utah
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Salt Lake City, Utah, United States, 84124
- Icon Slc Cru
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Males aged 18 to 60 years, inclusive
- Able to understand the study and provide signed, written informed consent
- Able to read and understand the language of the informed consent form and other study-related materials
- Willing and able to complete all protocol-required study visits and procedures
- Male participants with female partners of childbearing potential must use condoms during the treatment and until 125 days after the dose of study drug.
Exclusion Criteria:
- Any history of clinically significant lung disease as determined by the Investigator
- Any other concurrent active medical condition determined clinically significant by the Investigator
- Any current skin conditions or rashes that involve the planned area of injection
- Body mass index (BMI) >30 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
- Current infection with hepatitis B, hepatitis C, or human immunodeficiency virus (HIV)
- Planning to contribute to pregnancy during the study and up to 125 days after the participant's dose of study drug
- History of severe depression, psychosis, or suicidal ideation, as determined by the Investigator, within 5 years 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
- Known allergy to MTX-463 or any of its excipients, or a history of a prior allergic reaction to a monoclonal antibody therapeutic
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Placebo Comparator: Placebo
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Placebo
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Experimental: MTX-463
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MTX-463 is an immunoglobin G1 (IgG1) monoclonal antibody directed against WNT-inducible signaling pathway protein 1 (WISP1).
WISP1 (aka CCN-4) is a matricellular protein that appears to be upregulated locally in response to certain chronic diseases, including IPF, and malignancies.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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PK will be evaluated by area under the plasma concentration versus time curve from time zero to t (AUC0-t) of MTX-463
Time Frame: 22 Days
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Unit of Measure: Nanogram·hour per milliliter (ng·h/mL)
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22 Days
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PK will be evaluated by Maximum Observed Plasma Concentration (Cmax) of MTX-463
Time Frame: 22 Days
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Unit of measure: ng/mL
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22 Days
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Comparisons of Maximum Observed Plasma Concentration (Cmax) of MTX-463 will be made to historical single-dose 4-mg/kg IV data.
Time Frame: 22 Days
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Unit of measure: ng/mL
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22 Days
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Comparisons of area under the plasma concentration versus time curve from time zero to t (AUC0-t) of MTX-463 will be made to historical single-dose 4-mg/kg IV data.
Time Frame: 22 Days
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Unit of Measure: Nanogram·hour per milliliter (ng·h/mL)
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22 Days
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Incidence of serious adverse events (SAEs)
Time Frame: 22 days
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Number SAEs as defined by protocol criteria
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22 days
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Incidence of Treatment Emergent Adverse Events (TEAEs)
Time Frame: 22 days
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Number of TEAEs summarized by seriousness and maximum severity as defined by protocol criteria
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22 days
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Incidence of Treatment Related Adverse Events (TRAEs)
Time Frame: 22 days
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Number of TRAEs summarized by seriousness and maximum severity as defined by Protocol criteria
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22 days
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Clinically significant findings on clinical laboratory tests
Time Frame: 22 days
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Clinically significant findings in hematology, clinical chemistry, urinalysis, and other protocol-specified laboratory parameters will be summarized. Units of Measure: Standard laboratory units (e.g., g/dL, mEq/L, mg/dL, increase by factor) |
22 days
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Descriptive statistics on vital signs.
Time Frame: 22 Days
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Descriptive statistics on temperature (Units: degrees Celcius), pulse rate (Units: beats per minute), respiratory rate (Units: breaths per minute), and blood pressure (Units: mmHg) will be assessed for change from Baseline, when applicable, and summarized by timepoint.
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22 Days
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Descriptive statistics on electrocardiograms (ECGs)
Time Frame: 22 Days
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Descriptive statistics on ECG parameters (including but not limited to PR interval, QRS interval, QT, QTcF, and RR) will be assessed for change from Baseline, when applicable, and summarized by timepoint. Units: msec |
22 Days
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Descriptive statistics on clinical laboratory tests.
Time Frame: 22 Days
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Descriptive statistics on hematology, clinical chemistry, urinalysis, and other protocol-specified laboratory parameters will be assessed for change from Baseline, when applicable, and summarized by timepoint. Units of Measure: Standard laboratory units (e.g., g/dL, mEq/L, mg/dL, increase by factor) |
22 Days
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Incidence of injection site pain and injection site reactions
Time Frame: 22 days
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Number of incidents of injection site pain and injection site reactions as assessed by the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (V2.1)
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22 days
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Presence of Anti-Drug Antibodies (ADA)
Time Frame: 22 days
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Presence of ADAs against MTX-463 in serum as assessed by a validated ELICA assay.
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22 days
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Signal inhibition in the confirmatory assay of Anti-Drug Antibodies (ADA)
Time Frame: 22 days
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Signal inhibition in the confirmatory assay of Anti-Drug Antibodies (ADA) to assess the frequency with which positive signals are confirmed.
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22 days
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Titer of Anti-Drug Antibodies (ADA)
Time Frame: 22 days
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Titer of ADAs against MTX-463 in serum as assessed by a validated ELICA assay.
Units: titer units
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22 days
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Impact of Anti-Drug Antibodies (ADA)
Time Frame: 22 days
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To assess whether the presence of ADA impacts the concentration of MTX-463 and adverse events.
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22 days
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Collaborators and Investigators
Sponsor
Investigators
- Study Chair: Todd Astor, MD, Mediar Therapeutics
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Other Study ID Numbers
- MTX-463-I102
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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