Clinical trial NCT06324604: Safety, Pharmacokinetics, and Pharmacodynamics of MTX-101 in Healthy Adults and Patients
Official title: Safety, Pharmacokinetics, and Pharmacodynamics of MTX-101 in Healthy Adults and Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Healthy Volunteers
Celiac Disease
Type 1 Diabetes
Keywords: Healthy Volunteers
Celiac
Type 1 Diabetes
Lead sponsor: Mozart Therapeutics Australia Pty Ltd
Sponsor class: INDUSTRY
First posted: 2024-03-22
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
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 (CeD and/or T1D patients). Participants in Cohort B8 will be dosed with MTX-101 on Days 1 \& 29, then placebo on Day 57 or placebo on Day 1 and MTX-101 on days 29 \& 57. 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.
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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 ≤ 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.

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.
* Renal function calculated by the Chronic Kidney Disease-Epidemiology (CKD-EPI) equation with estimated glomerular filtration rate (eGFR) \&lt; 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.

Primary outcomes:
measure: Safety of single, ascending dose levels of MTX-101
timeFrame: Enrollment to 8 weeks post dose
measure: Safety of multiple, ascending dose levels of MTX-101
timeFrame: Enrollment to 11 weeks following the last dose
Secondary outcomes:
measure: pharmacokinetics (PK) of MTX-101
timeFrame: Enrollment to 11 weeks following the last dose
measure: pharmacokinetics (PK) of MTX-101
timeFrame: Enrollment to 11 weeks following the last dose
measure: pharmacokinetics (PK) of MTX-101
timeFrame: Enrollment to 11 weeks following the last dose
measure: anti-drug antibody (ADA) formation
timeFrame: Enrollment to 11 weeks following the last dose
Other outcomes:
measure: pharmacodynamics (PD) of MTX-101
timeFrame: Enrollment up to 11 weeks following the last dose
measure: Receptor occupancy of MTX-101
timeFrame: Enrollment up to 11 weeks following the last dose
Locations:
city: Auchenflower
country: Australia
facility: Wesley Research Institute
state: Queensland
city: Herston
country: Australia
facility: Nucleus Network Brisbane
state: Queensland
city: Melbourne
country: Australia
facility: The Royal Melbourne Hospital
state: Victoria
city: Box Hill
country: Austria
facility: Eastern Health; Box Hill Hospital
state: Victoria
Study officials:
References: