Neurodegenerative diseases Nervous System Diseases
Conditions
Interventions
Subjects receive a single subcutaneous dose of SBT-272 or placebo on one occasion in the single ascending dose (SAD) part of the study.
Subjects receive daily subcutaneous doses of SBT 272 or placebo
Sponsors
Stealth BioTherapeutics (United States)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Willing and able to provide a signed informed consent form (ICF) prior to participation in any study-related procedures 2. Healthy subjects aged 18 to 55 years (inclusive) at the time of informed consent 3. Body mass index =18.5 and =32.0 kg/m2 at screening and body weight =120kg 4. Must, in the opinion of the PI, be in good health based upon medical history and physical examination, including lack of clinically significant abnormalities during vital signs, ECG, and laboratory assessments at screening and Day-1 5. Willing to comply with all study restrictions 6. Women of childbearing potential must confirm at least one of the following highly effective methods of birth control will be adhered to from the Screening Visit until 90 days after the last dose of IMP: a. Abstinence from heterosexual intercourse, when it is in line with the preferred and usual lifestyle of the subject. Subject agrees to use the contraceptive methods described below should they become heterosexually active b. Maintenance of a monogamous relationship with a male partner who has been surgically sterilized by vasectomy (the vasectomy procedure must have been conducted at least 60 days prior to the Screening Visit or confirmed via sperm analysis) c. Barrier method (e.g., condom or occlusive cap) with spermicidal foam/gel/film/ cream AND either hormonal (may be either a combined estrogen and progesterone-containing form or a progesterone-only form) contraception (oral, implanted, or injectable) associated with inhibition of ovulation, an intrauterine device (IUD), or an intrauterine hormone-releasing system (IUS) at least 30 days prior to the Screening Visit d. Bilateral tubal occlusion Note: Non-childbearing potential is defined as subject confirmed: a. Surgical sterilization (e.g., bilateral oophorectomy, hysterectomy, or bilateral salpingectomy) at least 60 days prior to the Screening Visit b. Postmenopausal (defined as permanent cessation of menstruation for at least 12 consecutive months without an alternative medical cause prior to screening) with follicle stimulating hormone = 40 mIU/mL at screening 7. Male subjects with female partners of child-bearing potential must use a condom and confirm use of another highly effective form of contraception from the Screening Visit until 90 days after the last dose of IMP: a. Surgically sterilized by vasectomy (the vasectomy procedure must have been conducted at least 60 days prior to the Screening Visit or confirmed via sperm analysis) or having undergone bilateral tubal occlusion at least 60 days prior to the Screening Visit b. Usage by the female partner of any form of hormonal contraception (i.e., either a combined estrogen and progesterone-containing form or a progesterone-only form, associated with inhibition of ovulation), an IUD, or an IUS plus usage by one of the partners of an additional spermicide-containing barrier method of contraception, both of which should be established prior to the start of the study (at least 30 days before screening) and continue for 90 days after the last dose of IMP c. Alternatively, male subjects with female partners of child-bearing potential may abstain from heterosexual intercourse, when it is in line with the preferred and usual lifestyle of the subject. Subject agrees to use the methods of contraception described above should they become heterosexually active Note: Male subjects with pregnant partners, partners of non-childbearing potential or same sex partners must use a co
Exclusion criteria
Exclusion criteria: 1. Serum potassium, calcium or sodium outside the normal reference range at screening (unless considered not clinically significant by the PI) a. Or any other clinically significant laboratory abnormalities as determined by the PI at screening, 2. Estimated glomerular filtration rate (eGFR) 400 mL within the 3 months prior to screening, 11. Fever greater than 37.5°C within 1 week of planned dosing, 12. Any disease or condition that might compromise the cardiovascular, hematological, renal, hepatic (including Gilbert’s Syndrome), pulmonary (including chronic asthma), endocrine (e.g., diabetes), central nervous, or gastrointestinal (including an ulcer) systems, 13. History of seizures or history of epilepsy (including childhood febrile convulsions), 14. History of significant mental illness, at the discretion of the PI, 15. Female subjects who are pregnant (determined by serum hCG at screening and/or urine hCG at screening or Day-1), planning to become pregnant, or lactating, 16. Subject has undergone an in-patient hospitalization within 30 days prior to screening, 17. Subject has a clinically significant hypersensitivity or allergy to any pharmaceutical agent at any time, 18. Presence or history of clinically significant allergy requiring treatment, as judged by the PI. Hay fever is allowed unless it is active, 19. Clinical evidence of current or recent (< 21 days prior to screening) COVID-19 (SARS-CoV-2) infection, 20. Subject has received study medication in a clinical study within 90 days prior to screening, 21. Subject has any prior or current medical condition that, in the judgment of the PI, would prevent the subject from safely participating in and/or completing all trial requirements or failure to satisfy the PI of fitness to participate for any other reason, 22. Subjects who are study site employees, or immediate family members of a study site or sponsor employee, 23. Subjects who report to have previously received SBT-272, 24. Subjects who have previously been enrolled in this study. Subjects may only participate in either the SAD or MAD part of the study, 25. Subjects who do not have suitable veins for m
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The collective safety and tolerability profile of single and multiple ascending doses of SBT-272 compared with placebo from the time of signing the informed consent form up until discharge from the study. Variables for comparative analysis between active (by dose level) and placebo subjects within each of the SAD and MAD portions of the study: 1. Incidence, type, severity of treatment emergent adverse events 2. Vital signs parameters, including change from baseline 3. 12-lead ECG parameters, including change from baseline 4. Clinical laboratory parameters (including serum tryptase and plasma histamine), including change from baseline 5. Physical examination findings, including change from baseline | — |
Secondary
| Measure | Time frame |
|---|---|
| Characterization of the following PK parameters for SBT-272 in plasma where possible and appropriate using blood samples taken at multiple timepoints up to 48 hours post final dose: Cmax, Tlag, Tmax, AUC0-24, AUC0-last, AUC0-inf, AUCextrap, t1/2, ?z z, CL/F, Vd/F and accumulation ratios | — |
Countries
England, United Kingdom
Contacts
Public ContactAnthony Abbruscato
Outcome results
None listed