None listed
Conditions
Brief summary
MTAI-1025 as a novel agent for the treatment of ulcerative colitis (UC), a debilitating chronic disease caused by inflammation in the colon and rectum. The primary purpose of this study is to test a new oral medication called MTAI-1025 to see if the medication is safe when given as a single dose or when given over 2 weeks of dosing. This study also assesses blood samples to understand how much of the medication is in the blood stream and the impact of food on how much medication is absorbed into the body. The hypothesis is that the new medication will be safe to take.
Interventions
This is a Phase 1, first-in-human study for MTAI-1025 interventional product. This a randomized study to assess the safety, tolerability, and PK of single (SAD) and multiple (MAD) ascending doses of oral MTAI-1025 in healthy participants. This study will be conducted in below mentioned phases-All study durations are per each participant and include a 28-day Screening period and the Follow-up.
Part A: SAD—randomized, double-blind, placebo-controlled, in up to 5 sequential cohorts; approximately 5
This is a Phase 1, first-in-human study for MTAI-1025 interventional product. This a randomized study to assess the safety, tolerability, and PK of single (SAD) and multiple (MAD) ascending doses of oral MTAI-1025 in healthy participants. This study will be conducted in below mentioned phases-All study durations are per each participant and include a 28-day Screening period and the Follow-up. Part A: SAD—randomized, double-blind, placebo-controlled, in up to 5 sequential cohorts; approximately 5 weeks. Part B: MAD (14 days treatment)—randomized, double-blind, placebo-controlled, in up to 3 sequential cohorts; approximately 7 weeks Part A: SAD Eligible participants in Part A will receive single ascending doses of MTAI-1025 in up to 5 sequential cohorts of 8 participants each. In each cohort, participants will be randomized to receive a single dose of MTAI-1025 or placebo in a 3:1 ratio (active to placebo) in a fasted state and in a double-blinded fashion, Participants remain as inpatients throughout treatment. Additional cohorts of participants may be added based on emerging data in a 3:1 ratio (active: placebo) in a fasted state and a double-blinded fashion. The starting dose for Part A will be 40 mg of MTAI-1025. The maximum dose escalation between cohorts will be no more than 3-fold. A dose level may be repeated or decreased, or a new dose cohort added as required, based on emerging results. The first dose in each cohort will be administered to a sentinel group of 2 participants in which 1 participant will receive MTAI-1025 and 1 participant will receive placebo in a blinded fashion. The remaining participants will be dosed after at least 24 h postdose and only after review of safety data (including reported adverse events [AEs], clinical laboratory results, and ECGs) from these 2 participants by the Medical Monitor and the Investigator. For the next 6 participants, 5 will receive MTAI-1025 and 1 will receive placebo. Each participant will be in 1 study period to receive a single-day oral dose of MTAI-1025 or matching placebo after an overnight fast of at least 8 h. Dose escalation decisions will be based on satisfactory review of blinded safety, tolerability, and available PK data by the Investigator and the Medical Monitor from at least 6 participants who have completed Day 3 of the previous dose. All participants will be admitted to the clinical research unit on Day -1 and remain in the unit for approximately 3 days after dosing. Scheduled safety and PK assessments will be conducted while participants remain in the unit as summarized in the Schedule of Events. Participants will be allowed to enroll in only a single cohort and will not be permitted to enroll in another part of the study. Part B: MAD Part B may begin before the completion of Part A. However, participants in Part B will be enrolled only after Part A cohorts at doses equal to or higher than the proposed first dose for Part B have completed and a blinded review of data from these cohorts by the Investigator and Medical Monitor indicates adequate safety, tolerability, and PK. It is expected that up to 3 cohorts of 8 participants each (Cohorts 1-3) will be enrolled in the MAD portion of the study. In each cohort, participants will be randomized in a double-blinded fashion to receive MTAI-1025 or placebo in a 3:1 ratio (active to placebo). Participants will receive daily doses of MTAI-1025 or matching placebo for 14 consecutive days following an overnight fast (~8 h). An additional cohort (Cohort 4) may be added after review of data in the previous cohorts. The maximum dose escalation between cohorts will be no more than 3-fold. Dose escalation decisions will be based on satisfactory review of blinded safety, tolerability, and available PK data by the Investigator and the Sponsor from at least 6 participants who have completed Day 3 of the previous dose. All participants will be admitted to the clinical research unit on Day -1 and remain in the unit for approximately 15 days after first dose. Scheduled safety and PK assessments will be conducted while participants remain in the unit as summarized in the Schedule of Events. Participants will be allowed to enroll in only a single cohort and will not be permitted to enroll in another part of the study.
Sponsors
Montai Therapeutics, Inc.
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Participants eligible for enrollment in the study must meet all the following criteria: 1. Males and females 18 to 55 years of age, inclusive. 2. Medically healthy with no clinically significant medical history, physical examination, laboratory results, vital signs, or ECGs at Screening and admission day. 3. Body mass index (BMI) of 18 to 40 kg/m2 4. Non-smoker or casual smoker (up to 5 cigarettes per week) who are willing to abstain from smoking for equal to 2 weeks prior to dosing and throughout the study. 5. Females of childbearing potential involved in any sexual intercourse that could lead to pregnancy: the participant must agree to use two highly effective contraceptive methods from Screening until at least 1 week after the last study drug administration. a. Female participants of childbearing potential must have a negative serum pregnancy test at Screening and on admission day. 6.Females not of childbearing potential or postmenopausal defined as follows: a. Have had surgical sterilization (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) b. Have had amenorrhea for minimum of 1 year with confirmation by levels of follicle stimulating hormone (FSH) testing 7. For male participants involved in any sexual intercourse that could lead to pregnancy, participant must agree to use 2 highly effective contraceptive methods from Day 1 until at least 12 weeks after the last study drug administration. Note: No restrictions are required for males who have undergone a documented vasectomy at least 4 months prior to Screening. If vasectomy procedure is not documented or was performed less than 4 months prior to Screening, males must follow the same contraception as for non-vasectomized participants. 8. Capable of giving signed informed consent and able to comply with study procedures.
Exclusion criteria
Participants will be excluded from the study if any of the following criteria are met: 1. Any acute or chronic medical condition that would prevent the participant from complying with the procedures or place the participant at risk if they participate in the study. 2. Positive for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (anti-HCV), or human immunodeficiency virus (HIV) at Screening. 3. Any history of malignancy in the last 5 years, excluding non-melanoma skin cancer that has been completely resected. 4. Any history of significant liver disease. 5. Positive drug screen at Screening or on the admission day visit. 6. Participation in another investigational drug trial within 3 months of screening or, if known, 5 half-lives of the investigational drug (whichever is longer). 7. History of drug/alcohol abuse in the last year. 8. Alcohol consumption within 5 days of randomization and/or unwilling to abstain during the study. 9. Use of any medications that are inhibitors or inducers of cytochrome P450 (CYP)3A4 within 4 weeks prior to randomization and unwilling and/or unable to avoid these medications throughout the treatment duration 10. Use of any medications, dietary supplements including vitamins and herbal preparations, or non-prescription drugs, susceptible to altering absorption, affecting gastrointestinal motility, changing the gastric pH, increasing or decreasing the metabolism and excretion of MTAI-1025. 11. Use of any NRF2 agonists within 2 weeks of screening 12. History of infection requiring: a. Hospitalization or parenteral antimicrobial therapy within 2 months prior to Screening OR b. Treated with oral antimicrobial therapy within 2 weeks prior to Day 1. 13. Current, recent, or suspected infection within 2 weeks of Screening of SARS-CoV-2/COVID-19. 14. Recent vaccination with live attenuated vaccines within 30 days prior to Screening. 15. Unable to tolerate oral medication. 16. Allergy to MTAI-1025 or any component of the investigational product. 17. Blood donation or significant blood loss (greater than 500 mL) within 30 days prior to Screening. 18. Estimated GFR by 2021 CKD-EPI creatinine equation of upper limit of normal (ULN) • Total bilirubin greater than ULN • Hemoglobin lesser than 11.0 g/dL • White blood cell count lesser than 4.5 × 109/L • Platelet count lesser than 150 × 109/L
Outcome results
None listed