None listed
Conditions
Brief summary
This study is intended to study the safety and tolerability of a new investigational medication, MTX-474 in healthy adults. The study is "randomized", meaning that the study drug will be compared against a placebo comparator. MTX-474 as well as Placebo will be administered intravenously to study volunteers over the course of 1 hour, and safety assessments (Clinical Labs, ECG, Physical Examinations) will be performed at various timepoints throughout the study.
Interventions
This is a randomised, 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 by a qualified designee of the study doctor intravenously over 60 minutes in healthy adults. The SAD portion of the study will consist of 6 planned dosing cohorts each comprising 8 healthy participants. The starting dose will be 0.125mg/kg (Cohort 1) with subsequent pla
This is a randomised, 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 by a qualified designee of the study doctor intravenously over 60 minutes in healthy adults. The SAD portion of the study will consist of 6 planned dosing cohorts each comprising 8 healthy participants. The starting dose will be 0.125mg/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). Within each cohort, participants will be randomly assigned to receive MTX-474 or matched placebo. The MAD portion of the study will consist of 4 planned dosing cohorts administered once weekly (QW) for 4 infusions. 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 cohorts may be added as long as no Dose-Limiting Toxicity (DLT) emerges. A cumulative review of safety and tolerability of MTX-474 will be conducted by the study Investigator, Medical Monitor, and Sponsor's Responsible Medical Officer (SRMO) to inform dose escalation decisions for the next dose cohort. The Investigator, Medical Monitor, and SRMO will also verify that none of the stopping criteria for safety parameters was met before proceeding.
Sponsors
Mediar Therapeutics
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver)
Eligibility
Sex/Gender
All
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
- All genders, ages 18 to 60 years, inclusive - 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 - Willing to refrain from ingestion of alcohol from 7 days before Screening until the last study visit - Agrees to not donate egg or sperm (if applicable) from the time of first infusion until 125 days after the final dose; additionally agrees to not donate blood from 56 days prior to the time of first infusion until 90 days after the last study visit, or platelets/plasma 14 days prior to the time of first infusion until 90 days after the last study visit. - All participants assigned female at birth must have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Baseline. - Participants are required to follow specific contraception measures as follows: Participants assigned male at birth must use a condom (even if vasectomized) at the time of Screening and for 125 days after the final dose. Participants assigned female at birth must be of non-childbearing potential (defined as either at least 6 months surgically sterilized or at least 1 year postmenopausal and confirmed by FSH (Follicle Stimulating Hormone) level >40U/L) OR, if of childbearing potential (defined as not sterilized via bilateral oophorectomy, or hysterectomy, ; still menstruating; or <1 year has passed since the last menses, if menopausal), must use a combination of 1 highly effective method of contraception and 1 effective method of contraception . This contraceptive practice should begin at least 28 days before the first dose of study drug, continue during the study, and persist for 65 days after the final dose of study drug, if applicable.
Exclusion criteria
Any concurrent active medical condition determined clinically significant by the Investigator - Body mass index (BMI) >32 kg/m2. - Use of any systemic immunosuppressant medications, medications to treat diabetes, antipsychotics, anticoagulants, or other prescription medications other than oral contraceptives within 90 days of Screening that, as determined by the Investigator, could confound their participation in the study - 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, positive hepatitis B core antibody (HBcAb), hepatitis C, or human immunodeficiency virus (HIV) as evidenced by a positive hepatitis B surface antigen (HbsAg) at Screening or a positive HIV test at Screening. For hepatitis C, a positive hepatitis C antibody (anti-HCV) test is exclusionary unless the participant has previously been treated for hepatitis C, in which case they would be eligible with a negative HCV RNA. - Currently pregnant, lactating, or planning to conceive or contribute to pregnancy during the trial and up to 28 days after the participant’s last dose of study drug, if applicable - History of severe depression, psychosis, or suicidal ideation, as determined by the Investigator, 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). - Donation of blood within 28 days of Screening. - 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, including the following: Hemoglobin outside of the normal range for the study laboratory Absolute neutrophils outside of the normal range for the study laboratory White blood cells outside of the normal range for the study laboratory Platelet count outside of the normal range for the study laboratory - Any clinically significant abnormality on any of the screening ECGs - Alanine aminotransferase or aspartate aminotransferase up to 1.2 times the upper limit of normal - 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
Outcome results
None listed