Healthy Volunteers, Type 1 Diabetes
Conditions
Keywords
Healthy Volunteers, Type 1 Diabetes
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
A Phase 1, Part A -prospective, randomized, single-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). Part B - A multi-center, randomized, open-label study to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of MTX-101 in participants with type 1 diabetes (T1D).
Interventions
DRUGPlacebo
MTX-101
DRUGMTX-101
MTX-101 (bispecific CD8 Treg modulator)
Sponsors
Mozart Therapeutics Australia Pty Ltd
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
Part A will enroll Healthy Adult Volunteers will be randomized, double-blind, placebo-controlled, single ascending dose (SAD), randomized to MTX-101 or placebo in a 1:1 ratio for the first 2 participants (sentinel dosing) and a 3:1 ratio thereafter. Participants in the multiple ascending dose (MAD) will be randomized in a 3:1 ratio and be dosed on Days 1 and 22. Part B of this study plans to enroll at least 24 (up to 44) participants with CeD or T1D, randomized in a 1:1 ratio, in 2 sequential cohorts. Approximately 12 CeD and 12 T1D patients will be enrolled in Part B, with the option to enroll up to a maximum of 44 total (T1D patients). Participants in Cohort B8 will be dosed with MTX-101 on Days 1 & 29. Participants in Cohort B9 will be dosed with MTX-101 or placebo on Day 1 and MTX-101 on Day 29. Patients will be followed for 6 months after the first dose.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* 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 ≤ 35 kg/m2 AND body weight ≥ 55 and ≤ 120 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.
Exclusion criteria
* 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. * Prior or concurrent malignancies. * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| pharmacokinetics (PK) of MTX-101 | Enrollment to 11 weeks following the last dose | Characterize the pharmacokinetics (PK) of MTX-101 by measuring the maximum time of occurrence for maximum plasma drug concentration (Cmax) |
| 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. |
Countries
Australia
Contacts
CONTACTHeather Director, Clinical Operations
Outcome results
None listed