HealthyPhase 1NCT06535841
A First-in-Human Safety Trial of MTX-474
A Phase 1 study testing MTX-474 in people with Healthy, run by Mediar Therapeutics at 1 site in Australia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- MTX-474
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 78 participants
- Where
- 1 siteAustralia
- Study dates
- 10 Jul 2024to 24 Apr 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: MTX-474-S101: A Phase 1 Randomized, Double-Blind, Dose-Escalating Study to Assess the Safety, Tolerability, and Pharmacokinetics of MTX-474 in Healthy Adults
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.
Read the detailed 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-474 administered in healthy adults.
SAD Portion
The SAD portion of the study will consist of 6 planned dosing cohorts each comprising 8 healthy participants. The starting dose will be 0.125 mg/kg (Cohort 1) with subsequent planned doses of 0.25 mg/kg (Cohort 2), 0.5 mg/kg (Cohort 3), 1 mg/kg (Cohort 4), 2 mg/kg (Cohort 5), and 4 mg/kg (Cohort 6). 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-474 or matched placebo. The first 2 participants (sentinel participants) within each cohort will be randomized 1:1 to receive MTX-474 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, the additional 6 participants will be randomized to study drug (n=5 MTX-474; n=1 placebo).
Each participant will undergo assessments at specified timepoints on Days 1 through 29. End-of-Study (EOS) procedures will be completed on Day 29 or upon early termination (ET). An End-of-Follow-up (EOF) assessment of PK and ADA will be completed on Day 29.
MAD Portion
The MAD portion of the study will consist of 4 planned dosing cohorts. Each cohort will comprise 8 healthy participants (n=6 MTX-474; n=2 placebo). The starting dose will be 0.5 mg/kg (Cohort 1) with subsequent planned doses of 1 mg/kg (Cohort 2), 2 mg/kg (Cohort 3), and 4 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.
On Day 1, participants will be randomized to receive either MTX-474 or matched placebo. The randomized participants will receive a dose of study drug on Days 1, 8, 15, and 22. Participants will be housed inpatient from Day -1 through Day 2, Days 7 through 9, 14 through 16, and 21 through 23. All other visits will be conducted in the outpatient setting. Each participant will undergo assessments at specified timepoints on Days 1 through 50. 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 50.
Safety and tolerability of MTX-474 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 alternative doses.
- Conditions
- Healthy
- Being tested
- MTX-474, Placebo
- Keywords
- MTX-474-S101, MTX-474, Healthy Volunteer, MAD, SAD, Adult, Healthy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MTX-474Biological
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.
PlaceboOther
Matching Placebo - Normal Saline
| Study group | Role | What they receive |
|---|---|---|
| MTX-474 | Experimental | Biological: MTX-474 Receives: Biological: MTX-474 |
| Placebo | Placebo comparator | Placebo Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
These assessments will be summarized as:
Change from Baseline in bound EphrinB2 levels Change from Baseline in free EphrinB2 levels Change from Baseline in the percent phorphoEphB4 (pEpB4) positive cells and ratio of pEpB4 to total EphB4 positive cells
Measured: Through Day 29 (SAD Cohort) or Day 50 (MAD Cohort)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2024
- Study start10 Jul 2024
- Primary completion24 Apr 2025
- Study completion24 Apr 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 78 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mediar Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jeffrey Bornstein, MD, Study director, Mediar TherapeuticsGloria Wong, PhD, MBBS, Principal investigator, Nucleus Network Brisbane
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06535841
- Sponsor's protocol ID
- MTX-474-S101
- Status last verified
- May 2025
- First submitted
- 30 Jul 2024
- Last updated
- 18 May 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MTX-474-S101: A Phase 1 Randomized, Double-Blind, Dose-Escalating Study to Assess the Safety, Tolerability, and Pharmacokinetics of MTX-474 in Healthy Adults
- ClinicalTrials.gov ID
- NCT06535841
- Acronym / sponsor ID
- MTX-474-S101
- Conditions
- Healthy
- Keywords
- MTX-474-S101, MTX-474, Healthy Volunteer, MAD, SAD, Adult, Healthy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 78 participants (actual)
- Lead sponsor
- Mediar TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 10 Jul 2024 (actual)
- Primary completion
- 24 Apr 2025 (actual)
- Study completion
- 24 Apr 2025 (actual)
- First posted
- 2 Aug 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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-474 administered in healthy adults.
SAD Portion
The SAD portion of the study will consist of 6 planned dosing cohorts each comprising 8 healthy participants. The starting dose will be 0.125 mg/kg (Cohort 1) with subsequent planned doses of 0.25 mg/kg (Cohort 2), 0.5 mg/kg (Cohort 3), 1 mg/kg (Cohort 4), 2 mg/kg (Cohort 5), and 4 mg/kg (Cohort 6). 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-474 or matched placebo. The first 2 participants (sentinel participants) within each cohort will be randomized 1:1 to receive MTX-474 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, the additional 6 participants will be randomized to study drug (n=5 MTX-474; n=1 placebo).
Each participant will undergo assessments at specified timepoints on Days 1 through 29. End-of-Study (EOS) procedures will be completed on Day 29 or upon early termination (ET). An End-of-Follow-up (EOF) assessment of PK and ADA will be completed on Day 29.
MAD Portion
The MAD portion of the study will consist of 4 planned dosing cohorts. Each cohort will comprise 8 healthy participants (n=6 MTX-474; n=2 placebo). The starting dose will be 0.5 mg/kg (Cohort 1) with subsequent planned doses of 1 mg/kg (Cohort 2), 2 mg/kg (Cohort 3), and 4 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.
On Day 1, participants will be randomized to receive either MTX-474 or matched placebo. The randomized participants will receive a dose of study drug on Days 1, 8, 15, and 22. Participants will be housed inpatient from Day -1 through Day 2, Days 7 through 9, 14 through 16, and 21 through 23. All other visits will be conducted in the outpatient setting. Each participant will undergo assessments at specified timepoints on Days 1 through 50. 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 50.
Safety and tolerability of MTX-474 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 alternative doses.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MTX-474 | Experimental | Biological: MTX-474Biological: MTX-474 |
| Placebo | Placebo comparator | Other: PlaceboPlacebo |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MTX-474MTX-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. | Biological | MTX-474 |
| PlaceboMatching Placebo - Normal Saline | Other | Placebo |
Primary outcome
Incidence of Treatment-Related Adverse Events in healthy volunteers
Time frame: Through Day 29 (SAD Cohort) or Day 50 (MAD Cohort)
Clinical Safety Labs are collected, and Adverse Events are assessed in both inpatient and outpatient clinic visits
MTX-474 PK by dose will be evaluated for Cmax, as feasible
Time frame: Through Day 29 (SAD Cohort) or Day 50 (MAD Cohort)
Blood serum samples will be collected at protocol-specified timepoints throughout the study
Serum sample results will be summarized for presence of Anti-Drug Antibodies during the SAD and MAD portions of the study
Time frame: Through Day 29 (SAD Cohort) or Day 50 (MAD Cohort)
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.
MTX-474 PK by dose will be evaluated for AUC0-t, as feasible
Time frame: Through Day 29 (SAD Cohort) or Day 50 (MAD Cohort)
Blood serum samples will be collected at protocol-specified timepoints throughout the study
MTX-474 PK by dose will be evaluated for AUC0-tau (MAD only), as feasible
Time frame: Through Day 29 (SAD Cohort) or Day 50 (MAD Cohort)
Blood serum samples will be collected at protocol-specified timepoints throughout the study
MTX-474 PK by dose will be evaluated for AUC0-∞, as feasible
Time frame: Through Day 29 (SAD Cohort) or Day 50 (MAD Cohort)
Blood serum samples will be collected at protocol-specified timepoints throughout the study
1 secondary outcome
Blood serum samples will be collected to assess the target engagement of MTX-474 in healthy adult participants
Time frame: Through Day 29 (SAD Cohort) or Day 50 (MAD Cohort)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeffrey Bornstein, MD study director
Mediar Therapeutics
Gloria Wong, PhD, MBBS principal investigator
Nucleus Network Brisbane
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MTX-474 in people with Healthy, run by Mediar Therapeutics at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment-Related Adverse Events in healthy volunteers (time frame: Through Day 29 (SAD Cohort) or Day 50 (MAD Cohort)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 May 2025.