Healthy Adult Participants
Conditions
Brief summary
SAB01 is an investigational bispecific monoclonal antibody targeting mast cells. This first-in-human Phase 1 clinical trial evaluates the safety, pharmacokinetics, and pharmacodynamics of single ascending doses of SAB01 in healthy adult participants.
Detailed description
This is a first-in-human, randomized, double-blind, placebo-controlled, single ascending dose (SAD) study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of SAB01 administered subcutaneously (SC) and intravenously (IV) in healthy participants. The design comprises 7 planned cohorts (6 SC and 1 IV) and up to 4 optional cohorts (up to 3 additional SC and up to 1 additional IV) for up to a maximum of 88 participants enrolled. The Safety Review Committee will oversee dose escalation. Within each cohort, 8 participants will be randomized 6:2 to SAB01 or placebo Optional cohorts may be added to evaluate select SC and IV dose levels selected based on emerging safety, PK, and PD data and Safety Review Committee review. IV dose levels will not exceed dose levels previously evaluated by SC administration.
Interventions
DRUGSubcutaneous (SC) single dose of SAB01
Single-dose administration of SAB01 by SC administration.
DRUGIntravenous (IV) infusion of SAB01
Intravenous doses of SAB01 via IV infusion.
DRUGPlacebo SC
Single-dose of placebo by subcutaneous (SC) administration.
Placebo administration via IV infusion.
Sponsors
Santa Ana Bio
Altasciences Company Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Provision of signed and dated ICF. 2. Stated willingness to comply with all study procedures and availability for the duration of the study. 3. Healthy adult male or female aged at least 18 years but not older than 55 years. 4. Body mass index (BMI) within 18.0 to 32.0 kg/m2 inclusive, and up to a maximum body weight of 100 kg at Screening. 5. Non- or ex smokers. Participants must not have used any tobacco products within 6 months prior to Screening. Participants who have discontinued smoking or the use of nicotine or nicotine-containing products for at least 3 months prior to Screening may be enrolled at the discretion of the Investigator 6. Have no clinically significant diseases captured in the medical history or evidence of clinically significant findings on the physical examination (including vital signs) and/or electrocardiogram (ECG), as determined by an Investigator 7. Have clinical laboratory values within the normal range or, if abnormal, deemed not clinically significant by the Investigator (following consultation with the Sponsor, as appropriate). 8. Serum tryptase levels within clinically accepted normal ranges (ie, ≥ 1.4 to ≤11.5 µg/L) at Screening.
Exclusion criteria
1. Female who is breastfeeding or is pregnant according to the pregnancy test at Screening or on Day -1, or is planning to become pregnant any time during the study and for 8 months after study drug administration. 2. Body temperature ≥ 38°C/100.4 F or symptomatic viral or bacterial infection within 2 weeks prior to Screening, or active or acute infection requiring systemic antibiotic treatment (oral or IV) within 4 weeks prior to Screening. 3. History of clinically significant anaphylaxis, food allergies, asthma, or allergies (chronic or seasonal) requiring medication, as determined by an Investigator. 4. Known or suspected intolerance to SAB01 or any related products (including excipients of the formulations). 5. History of clinically significant diseases within 5 years prior to study drug administration. 6. Clinically significant illness within 4 weeks of study drug administration. 7. Previous or concurrent malignancy with the following exceptions: 1. Adequately treated basal cell or squamous cell carcinoma, 2. In situ carcinoma of the uterine cervix or breast, treated curatively and without evidence of recurrence for at least 3 years prior to Screening. 8. History of alcohol or drug abuse (within 1 year of Screening). 9. History of benign neutropenia and/or an absolute neutrophil count of \< 2.0 × 109/L or 2.0 × 103/µL at Screening or on Day -1. 10. Use of any prescription drugs (with the exception of hormonal contraceptives or hormonal replacement therapy), over-the-counter (OTC) medications, vitamins, herbal medicines (including St. John's wort) or cannabis within 7 days or 5 half-lives (whichever is longer) prior to study drug administration, that in the opinion of an Investigator would put into question the status of the participant as healthy. Acetaminophen is permitted provided the total daily dose does not exceed 2 g per day. 11. Consumption of \> 21 alcohol units per week (where 1 unit = 284 mL of beer, 25 mL of 40% spirit, or a 125 mL glass of wine). 12. Currently enrolled in another investigational drug or device study, or less than 30 days or 5 half-lives of the prior investigational agent (whichever is longer) have passed since completion of another investigational drug or device study; or plans to enroll in another investigational drug or device study during participation in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability of single ascending doses of SAB01 | Day 1 through Day 113 | To assess the safety and tolerability of single ascending doses of SAB01 administered via subcutaneous (SC) and intravenous (IV) infusion in healthy participants |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma PK profile. | Day 1 through Day 113 | Maximum SAB01 concentration observed (Cmax). |
| Plasma PK profile | Day 1 through Day 113 | Time of maximum SAB01 concentration (Tmax) |
| Pharmacodynamic (PD) effects of SAB01 | Day 1 through Day 113 | Plasma concentration of tryptase over time |
| Absolute bioavailability | Day 1 through Day 113 | Fraction of SAB01 AUC after subcutaneous (SC) injection compared to AUC after intravenous (IV) infusion |
| Subcutaneous (SC) Clearance | Day 1 through Day 113 | Volume of plasma cleared of SAB01 compared to the fraction absorbed after SC injection (CL/F) |
| Intravenous clearance | Day 1 through Day 113 | volume of plasma cleared of SAB01 after IV infusion (CL) |
| Apparent volume of distribution | Day 1 through Day 113 | Apparent SAB01 volume of distribution during terminal elimination (Vz/F) after SC injection |
| Apparent Volume of Distribution | Day 1 through Day 113 | Apparent SAB01 volume of distribution during terminal elimination (Vz/F) after IV infusion |
| Half-life of SAB01 in plasma | Day 1 through Day 113 | Time for SAB01 plasma concentration to decrease by 50% (T1/2) |
| Volume of Distribution | Day 1 through Day 113 | Volume of distribution of SAB01 after IV infusion (Vss) |
| Immunogenicity of SAB01 | Day 1 through Day 113 | To evaluate the presence of anti-drug antibodies to SAB01 |
Countries
Canada, United States
Outcome results
None listed