Safety, Pharmacokinetics, and Pharmacodynamics of MTX-101 in Healthy Adults and Patients
- Conditions
- Celiac DiseaseHealthy VolunteersType 1 Diabetes
- Interventions
- Drug: Placebo
- Registration Number
- NCT06324604
- Lead Sponsor
- Mozart Therapeutics Australia Pty Ltd
- Brief Summary
First in human study to understand the potential side effects of MTX-101, how long MTX-101 lasts in the human body, and how MTX-101 affects specific human immune cells.
- Detailed Description
This is a prospective, multi-center, randomized, double-blind, placebo-controlled, single ascending dose (SAD) and multiple ascending dose (MAD) study to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of MTX-101 in healthy adults (HA) and participants with celiac disease (CeD) and type 1 diabetes (T1D). This study will enroll HAs only in Part A and CeD and T1D patients only in Part B.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 96
- Adults, age ≥ 18 and ≤ 65 years at the time of anticipated dosing (Day 1).
- Healthy individuals without known current or chronic medical conditions, including no history of any autoimmune diseases, in the opinion of the Investigator.
- Body mass index (BMI) ≥ 18 kg/m2 and ≤ 32 kg/m2.
- Body weight ≥ 45and ≤ 100 kg.
- Negative Coronavirus Disease 2019 (COVID-19) test within 24 hours prior to each dose.
- Persons of child-bearing potential must have a negative pregnancy test and either abstain from sex or use highly effective method(s) of birth control from Day 1 through the duration of the study.
- Clinically significant findings in physical examination (PE), vital signs (blood pressure, heart rate, and body temperature), electrocardiogram (ECG), and safety laboratory parameters at Screening in the opinion of the Investigator.
- Renal function calculated by the Chronic Kidney Disease-Epidemiology (CKD-EPI) equation with estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m2 or abnormal level of proteinuria detected by dipstick at the time of Screening.
- Any disease or condition that, in the opinion of the Investigator, might significantly compromise the cardiovascular, hematological, renal, hepatic, pulmonary (including chronic asthma), endocrine (e.g., diabetes), central nervous, or gastrointestinal (including an ulcer) systems.
- Receipt of an investigational drug within 28 days or 5 half-lives (whichever is longer) of the investigational drug(s) prior to Day 1.
- Positive serology for human immunodeficiency virus (HIV) type 1 or 2, hepatitis (Hep) B surface antigen, or Hep C.
- Positive test results for drug screen, including alcohol, at the time of Screening or on Day 1 prior to randomization.
- Use of tobacco or nicotine-containing products more than the equivalent of 5 cigarettes/week within 30 days prior to (first) dosing.
Participants must abstain from nicotine use while inpatient.
- History of receiving a live vaccine within 1 month of Screening.
- History of splenectomy.
- History of COVID or influenza vaccine within 2 weeks prior to Screening.
- Planning to receive any vaccinations during the study period.
- History of recurrent infections of uncertain cause.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Cohort AS1 - Healthy Volunteers Placebo (n = 6): MTX-101, Dose level 1 IV or Placebo IV, Single dose Cohort AS1 - Healthy Volunteers MTX-101 (n = 6): MTX-101, Dose level 1 IV or Placebo IV, Single dose Cohort AS2 - Healthy Volunteers Placebo (n = 6): MTX-101, Dose Level 2 IV or Placebo IV, Single dose Cohort AS2 - Healthy Volunteers MTX-101 (n = 6): MTX-101, Dose Level 2 IV or Placebo IV, Single dose Cohort AS3 - Healthy Vounteers Placebo (n = 6): MTX-101, Dose Level 3 IV or Placebo IV, single dose Cohort AS4 - Healthy Volunteers Placebo (n =6): MTX-101, Dose Level 4 IV or Placebo IV, single dose Cohort AS5 - Healthy Volunteers Placebo (n = 6): MTX-101, Dose level 6 IV or Placebo IV, Single Dose Cohort AM1 - Healthy Volunteers Placebo Cohort AM1 (n = 6): MTX-101, Dose Level 5 IV or Placebo IV, dosed on Days 1 and 22 for a total of 2 doses Cohort AM1 - Healthy Volunteers MTX-101 Cohort AM1 (n = 6): MTX-101, Dose Level 5 IV or Placebo IV, dosed on Days 1 and 22 for a total of 2 doses Cohort B8 - Celiac Disease or Type 1 Diabetes Patients Placebo * Dose Group 1 (n = 6): MTX-101 Dose Level 4 IV Day 1 and 29, placebo IV Day 57 * Dose Group 2 (n = 6): Placebo IV Day 1, MTX-101 Dose Level 3 IV Day 29 and 57 Cohort B9 -Celiac Disease or Type 1 Diabetes Patients Placebo Dose Group 1 (n = 6): MTX-101 Dose Level 5 IV Days 1 and 29 Dose Group 2 (n = 6): Placebo IV Day 1, MTX-101 Dose Level 5 IV (or the maximum tolerated dose in Part A MAD) Day 29 Cohort AS3 - Healthy Vounteers MTX-101 (n = 6): MTX-101, Dose Level 3 IV or Placebo IV, single dose Cohort AS4 - Healthy Volunteers MTX-101 (n =6): MTX-101, Dose Level 4 IV or Placebo IV, single dose Cohort AS5 - Healthy Volunteers MTX-101 (n = 6): MTX-101, Dose level 6 IV or Placebo IV, Single Dose Cohort B8 - Celiac Disease or Type 1 Diabetes Patients MTX-101 * Dose Group 1 (n = 6): MTX-101 Dose Level 4 IV Day 1 and 29, placebo IV Day 57 * Dose Group 2 (n = 6): Placebo IV Day 1, MTX-101 Dose Level 3 IV Day 29 and 57 Cohort B9 -Celiac Disease or Type 1 Diabetes Patients MTX-101 Dose Group 1 (n = 6): MTX-101 Dose Level 5 IV Days 1 and 29 Dose Group 2 (n = 6): Placebo IV Day 1, MTX-101 Dose Level 5 IV (or the maximum tolerated dose in Part A MAD) Day 29
- Primary Outcome Measures
Name Time Method Safety of multiple, ascending dose levels of MTX-101 Enrollment to 11 weeks following the last dose Assess the safety of multiple, ascending dose levels of MTX-101by evaluating the incidence, severity, and seriousness of treatment-emergent adverse events
Safety of single, ascending dose levels of MTX-101 Enrollment to 8 weeks post dose Assess the safety of single, ascending dose levels of MTX-101 by evaluating the incidence, severity, and seriousness of treatment-emergent adverse events
- Secondary Outcome Measures
Name Time Method pharmacokinetics (PK) of MTX-101 Enrollment to 11 weeks following the last dose Characterize the pharmacokinetics (PK) of MTX-101 by measuring the maximum plasma drug concentration (Cmax), minimum plasma drug concentration (Cmin), and area under the plasma drug concentration versus time curve from time 0 to last measurable concentration (AUC(0-t))
anti-drug antibody (ADA) formation Enrollment to 11 weeks following the last dose Evaluate incidence of anti-drug antibody (ADA) formation by measuring the detect the presence of anti-MTX-101 antibodies in participant's blood.
Trial Locations
- Locations (4)
Wesley Research Institute
🇦🇺Auchenflower, Queensland, Australia
Nucleus Network Brisbane
🇦🇺Herston, Queensland, Australia
The Royal Melbourne Hospital
🇦🇺Melbourne, Victoria, Australia
Eastern Health; Box Hill Hospital
🇦🇹Box Hill, Victoria, Austria