A Phase 1, Open-Label, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Migaldendranib (MGB) in Healthy Volunteers
Overview
- Phase
- Phase 1
- Status
- Not yet recruiting
- Sponsor
- Ashvattha Therapeutics, Inc.
- Enrollment
- 36
- Primary Endpoint
- Safety and Tolerability of MGB
Overview
Brief Summary
This is a Phase 1, open-label, multiple-dose study to evaluate the safety, tolerability, and PK of MGB after weekly subQ MGB administration in up to 36 healthy volunteers at 1 site in Australia.
Detailed Description
This is a Phase 1, open-label, multiple-dose study to evaluate the safety, tolerability, and pharmacokinetics (PK) of MGB administered following weekly subcutaneous dosing in healthy adult volunteers. Up to 36 participants will be enrolled at a single site in Australia.
The study includes a screening period of up to 27 days, an 18-day treatment period, and follow-up visits on Days 22 and 29. Participants will be enrolled into up to six sequential dose-escalation cohorts (up to six participants per cohort) using a sentinel dosing approach. Dosing includes weekly subcutaneous administration of MGB at escalating doses.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Healthy man or woman age 18 to 65 years, inclusive, at the Screening Visit
- •Has the ability to understand and sign the written ICF and local medical privacy authorization forms, which must be obtained prior to any study-related procedures being completed
- •Is in general good health, based upon the results of a medical history assessment, physical examination, vital signs, and laboratory profile, as judged by the Investigator
- •Female participants of non-childbearing potential must be either surgically sterile (hysterectomy, bilateral tubal ligation, salpingectomy, and/or bilateral oophorectomy at least 26 weeks before the Screening Visit) or postmenopausal, defined as spontaneous amenorrhea for at least 1 year, with follicle-stimulating hormone (FSH) in the postmenopausal range at screening, based on the central laboratory's ranges
- •All female participants of childbearing potential with male partners and male participants with female partners of childbearing potential must consent to use 2 (two) highly effective methods of contraception from start of study and for at least 90 days following the EOS visit or last dose of study treatment, whichever is later. Women of childbearing potential on hormonal contraceptives must be stable on the medication for at least 2 menstrual cycles prior to Day -
- •The following are acceptable methods of highly effective contraception:
- •Using twice the normal protection of birth control by using a condom AND one other form of contraception; either birth control pills (The Pill), or injectable birth control, birth control patch or contraceptive implant associated with inhibition of ovulation, or intrauterine device; or
- •Surgical sterilization as a single form of birth control: i.e., tubal ligation, hysterectomy, bilateral oophorectomy, vasectomy, or equivalently effective surgical form of birth control (with documented proof of the absence of sperm in the post-vasectomy ejaculate) at least 6 months prior to screening; or
- •True sexual abstinence for the duration of the study and for at least 12 weeks following the EOS visit or after the last dose of IP, whichever is later, is acceptable only when in line with the preferred and usual lifestyle of the participant.
- •Periodic abstinence (calendar, symptothermal, post ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea methods are not considered "true" abstinence and are not acceptable methods of contraception.
Exclusion Criteria
- •Evidence of clinically significant hematologic, renal, endocrine, pulmonary, cardiac, gastrointestinal (GI), hepatic, psychiatric, neurologic, immunologic, allergic disease (including multiple or clinically significant drug allergies), or any other condition that, in the opinion of the Investigator, might significantly interfere with the absorption, distribution, metabolism, or excretion of study drug, or place the participant at an unacceptable risk as a participant in this study
- •Evidence of systemic inflammation as measured by C-reactive protein above the upper limit of normal, as measured by the local lab
- •History of malignancy (other than successfully treated basal cell or squamous cell skin cancer)
- •History or presence of an abnormal electrocardiogram (ECG) that, in the opinion of the Investigator, is clinically significant
- •Laboratory results (serum chemistry, hematology, coagulation, and urinalysis) outside the normal range at screening and Check-in and considered clinically significant in the opinion of the Investigator. Any elevation of aspartate transaminase (AST) and alanine transaminase (ALT) above the upper limit of normal at screening and/or Check-in is exclusionary. One retest of an exclusionary laboratory result is allowed at the discretion of the Investigator
- •Has had an acute illness considered clinically significant by the Investigator within 30 days prior to screening
- •History of alcoholism or drug abuse within 1 year prior to screening or excessive alcohol consumption defined as \>14 standard drinks per week.
- •Has used any product containing nicotine within 30 days prior to screening or intends to use any product containing nicotine during the study (exception of ≤ 5 cigarettes per week)
- •Has had any immunizations (live vaccines) in the 4 weeks prior to screening; COVID-19 vaccination within 7 days of Day 1
- •Has used any prescription (with the exception of hormonal contraceptives) or over-the counter medication (with the exception of acetaminophen), vitamins/herbal supplements within7 days prior to Day 1
Arms & Interventions
MGB 200 mg
Participants receive MGB 200 mg administered subcutaneously once weekly on Days 1, 8, and 15 to evaluate safety, tolerability, and pharmacokinetics.
Intervention: MGB 200 mg (Drug)
MGB 400 mg
Participants receive MGB 400 mg administered subcutaneously once weekly on Days 1, 8, and 15 following Safety Review Committee approval.
Intervention: MGB 400 mg (Drug)
MGB 600 mg
Participants receive MGB 600 mg administered subcutaneously once weekly on Days 1, 8, and 15, contingent upon acceptable safety and tolerability in prior cohorts.
Intervention: MGB 600 mg (Drug)
Outcomes
Primary Outcomes
Safety and Tolerability of MGB
Time Frame: Varying timepoints through end of treatment, up to approximately 22 days.
Safety will be assessed throughout the study by monitoring adverse events (AEs), including their incidence, severity, and relationship to study treatment. Additional safety assessments will include clinical laboratory evaluations (hematology, clinical chemistry, and urinalysis), physical examinations, and vital sign measurements, including pulse rate, blood pressure (BP), respiration rate, and tympanic temperature.
Secondary Outcomes
- Pharmacokinetic Parameter Area Under the Curve (AUC) for MGB(Varying timepoints through end of treatment, up to approximately 22 days.)
- Pharmacokinetic Parameter Maximum Concentration (Cmax) for MGB(Varying timepoints through end of treatment, up to approximately 22 days.)
- Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) for MGB(Varying timepoints through end of treatment, up to approximately 22 days.)
- Pharmacokinetic Parameter Total Clearance (CL) for MGB(Varying timepoints through end of treatment, up to approximately 22 days.)
- Pharmacokinetic Parameter Apparent Terminal Half-life (t1/2) for MGB(Varying timepoints through end of treatment, up to approximately 22 days.)