A Phase I Randomised, Double-Blinded, Placebo-Controlled, Single Ascending Dose Adaptive Design Study Assessing the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Intravenous SAB-142

INTERVENTION: This is a randomised, double‐blind, placebo‐controlled Phase One single ascending dose (SAD) study, with an adaptive Type One diabetes (T1D) patient arm, to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of SAB‐142 in healthy participants, and (if relevant) T1D patients. The study is planned for 5 dose levels and is planned to be conducted in healthy volunteers unless the adaptive criteria in the study are met. The adaptive criteria are based on the data collected in each cohort. This data includes clinical labs, Adverse Events and other data that is reviewed by the Safety Review Committee. If the protocol defined criteria are met, the study will be transitioned to patients with T1D as it could be more beneficial to continue dosing in patients with T1D rather than in HV. Despite this being a Phase 1 study, if the preclinical and other comparator data is confirmed, there could be benefit for the patients with Type 1 Diabetes. Healthy adult volunteers will be enrolled and randomised to 5 cohorts: ‐ Cohort 1 (ratio 2:1 active: placebo) ‐ Cohorts 2 to 5 (8 each cohort, ratio 3:1 active: placebo). The starting dose will be 0.03 mg/kg with 5 dose levels planned (up to 2.5 mg/kg). SAB‐142 will be administered intravenously (IV), as a single dose, at the following dose levels: ‐ Cohort 1: 0.03 mg/kg ‐ Cohort 2: 0.1 mg/kg ‐ Cohort 3: 0.5 mg/kg ‐ Cohort 4: 1.5 mg/kg ‐ Cohort 5: 2.5 mg/kg In the event that the adaptive T1D patient arm of the study proceeds, dosing of healthy volunteers (HVs) will cease and T1D patients will be enrolled and randomised (6 each cohort, 2:1 active: placebo). The starting dose for the T1D patients will be equivalent to the next dose administered to the HVs full coho CONDITION: Inflammatory and Immune System ‐ Autoimmune diseases Metabolic and Endocrine ‐ Diabetes Type 1 diabetes; ; Type 1 diabetes PRIMARY OUTCOME: To evaluate the safety and tolerability of SAB‐142 in healthy volunteers following ascending intravenous infusion doses in cohort 1, 2 and 3. Possible adverse reactions include infusion reactions, hypersensitivity reaction including anaphylaxis, fever, chills and headache.; ; Incidence, type, severity, and relationship of Treatment‐Emergent Adverse Events (TEAEs)/Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) and TEAEs leading to discontinuation of study treatment.; Change from baseline in vital signs; Change from baseline in 12 lead electrocardiogram (ECG) parameters; Change from baseline in clinical laboratory results (haematology, serum chemistry, coagulation and urinalysis)[ AE's are graded using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI‐CTCAE) (Version 5) and assessed continuously as they are reported or observed and reviewed during screening, pre dose Day ‐1, pre and during dose on Day 1 and then post dose from Day 1 through to Day 180 (EOS) or Early Termination Visit (ETV).; ; Vital Signs (Blood pressure and pulse rate is measured using a sphygmomanometer, respiratory rate using manual breath count and temperature oral thermometer) are assessed at Screening, Day 1 pre‐dose and every 15 minutes during the first hour of the infusion, then every 30 minutes for the next 2 hours and then hourly until the end of infusion (EOI). Post dose vital signs will be assessed at 10, 12 and 16 hours post start of infusion (SOI) and again at Day 2, Day 3, Day 5, Day 6, Day 7, Day 10, Day 14, Day 30, Day 45, Day 90, Day 120 and Day 180 (EOS or ETV). ; ; 12‐Lead ECG: ECG recordings will be obtained in triplicate at Screening, Day ‐1, Day 1 pre‐dose and then post dose at 8 and 24 hrs, then daily on day 2, day 3, day 4, day 5, day 6, day 7, day 10, day 14, day 30, day 90, and day 180 (EOS or ETV). ; ; Clinical Laboratory Evaluations: ; Blood sample for haematology will be collected during the Screening period between day ‐45 and day ‐15 and again between day ‐14 and day ‐2, pre dose at day ‐1, post dose on Day 1 at EOI, day 2, day 3, day 4, day 5, day 6, day 7, day 10, day 14, day 30, day 45, day 90, day 120, and day 180 (EOS or ETV). ; ; Blood sample for serum chemistry will be collected during the screening period between day ‐45 and day ‐15 and again between day ‐14 and day ‐2, pre dose at day ‐1, and post dose at 24, 48, and 96 hours post SOI and again at day 3, day 5, day 7, day 10, day 14, day 30, day 45, day 90, day 120, and day 180 (EOS or ETV). ; ; Blood sample for coagulation will be collected during the Screening period between day ‐45 and day ‐15, pre dose at day ‐1, post dose on Day 1 at EOI, day 2, day 3, day 4, day 6, day 7, day 10, day 14, day 30, day 45, day 90, and day 180 (EOS or ETV).; ; Urine sample for urinalysis will be collected at screening, pre dose at day ‐1, and post dose day 1 and at 8, 24, 48, 72 and 96 hours, then again at day 7, day 14, day 30, day 45, day 90, day 120, and day 180 (EOS or ETV). ] To evaluate the safety and tolerability of SAB‐142 in healthy volunteers following ascending intravenous infusion doses in cohort 4 and 5. Possible adverse reactions include infusion reactions, hypersensitivity reaction including anaphylaxis, fever, chills and headache.; ; Safety endpoints include:; Incidence, type, severity, and relationship of Treatment‐Emergent Adverse Events (TEAEs)/Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) and TEAEs leading to discontinuation of study treatment.; Change from baseline in vital signs; Change from baseline in 12 lead electrocardiogram (ECG) parameters; Change from baseline in clinical laboratory results (haematology, serum chemistry, coagulation and urinalysis)[ AE's are graded using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI‐CTCAE) (Version 5) and assessed continuously as they are reported or observed and reviewed during screening, pre dose Day ‐1, pre and during dose on Day 1 and then post dose from Day 1 through to Day 180 (EOS) or Early Termination Visit (ETV).; ; Vital Signs (Blood pressure and pulse rate is measured using a sphygmomanometer, respiratory rate using manual breath count and temperature oral thermometer) are assessed pre‐dose on Day 1 and every 15 minutes during the first hour of the infusion, then every 30 minutes for the next 2 hours and then hourly until the EOI. Post dose vital signs will be assessed at 10, 12 and 16 hours on Day 1. Vital signs are assessed again pre‐dose on Day 2 and every 15 minutes during the first hour of the infusion, then every 30 minutes for the next 2 hours and then hourly until the EOI . Post dose vital signs will be assessed at 10, 12 and 16 hours on Day 2. Vital signs will then be assessed again at Day 3, Day 5, Day 6, Day 10, Day 14, Day 30, Day 45, Day 90, Day 120 and Day 180 (EOS or ETV). ; ; 12‐Lead ECG: ECG recordings will be obtained in triplicate at Screening, Day ‐1, Day 1 pre‐dose and then post dose at 6hrs, 12 hrs and 24hrs, For patients in Cohort 4 and 5, 12‐lead ECG will be recorded pre‐dose on Day 2 and then post dose at 8 and 24 hrs then daily on day 3, day 4, day 5, day 6, day 7, day 10, day 14, day 30, day 90, and day 180 (EOS or ETV). ; ; Clinical Laboratory Evaluations: ; Blood sample for haematology will be collected during the Screening period between day ‐45 and day ‐15 and again between day ‐14 and day ‐2, pre dose at day ‐1 and post dose Day 1 at EOI. For patients in cohort 4 and 5, blood for haemtology will be collected pre‐dose at day 2, and once post dose at EOI day 2, day 3, day 4, day 5, day 6, day 7, day 10, day 14, day 30, day 45, day 90, day 120, and day 180 (EOS or ETV). ; ; Blood sample for serum chemistry will be collected at screening visit, pre dose at day ‐1, and pre‐start of second dose at day 2, then post dose at 48 hours, 96 hours, day 7, day 10, day 14, day 30, day 45, day 90, day 120, and day 180 (EOS or ETV). ; ; Blood sample for coagulation will be collected during the Screening period between day ‐45 and day ‐15, pre dose at day ‐1, post dose on Day 1 at EOI, For patients in cohort 4 and 5, blood for coagulation will be collected pre‐dose at day 2, post dose at the EOI on day 2, day 3, day 4, day 6, day 7, day 10, day 14, day 30, day 45, day 90, and day 180 (EOS or ETV).; ; Urine sample for urinalysis will be collected pre dose at day ‐1, and 8 hours post day 1 dose then again at pre dose day 2 and post day 2 dose at 32hrs, 48hrs, 72hrs, 96hrs, day 7, day 14, day 30, day 45, day 90, day 120, and day 180 (EOS or ETV). ] INCLUSION CRITERIA: Healthy volunteers will be included in the study only if they satisfy all the following criteria: 1. Must have given written informed consent before any study‐related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects; 2. Adult males and females, aged 18 to 45 years of age (inclusive) at the time of enrolment. 3. Body mass inde X(BMI) in the range of greater than or equal to 19.0 and less than or equal to 32.0 kg/m2 at screening with weight of greater or equal to than 45 kg for females and less than or equal to 50 kg for males 4. The subject is in good health and has no medical conditions of clinical significance that may impact the outcomes of the study, as determined by the Investigator based on medical and psychiatric history, physical evaluation, 12‐lead electrocardiogram (ECG), serum chemistry, haematology, coagulation, urinalysis at screening visits an SECONDARY OUTCOME: To evaluate the immunogenicity of SAB‐142 following ascending doses will be assessed via the presence of anti‐SAB‐142 antibodies including optional neutralising antibodies (nAbs) in serum [ Presence of anti‐SAB‐142 antibodies including optional nAbs in serum will be collected via venepuncture and assessed pre‐dose Day 1 and post dose on day 14, day 30, day 45, day 90, day 120, and day 180 (EOS or ETV). ] To evaluate the pharmacodynamics (PD) of SAB‐142 in healthy volunteers following ascending doses in cohorts 1, 2 and 3. ; PD parameters to be evaluated after SAB‐142 administration include: ; ‐ Changes in cytokine levels in plasma ; ‐ Percentage changes in peripheral blood mononuclear cell (PBMC) subpopulations [ ‐ Changes in cytokine levels in plasma will be collected via venepuncture at screening between day ‐14 and day ‐2, pre dose at Day 1, EOI day 1, and day 2, day 3, day 4, day 5, day 7, day 14, and day 30 post‐dose. ; ‐ Percentage changes in PBMC will be collected via venepuncture at screening between day ‐14 and day‐2, pre dose at Day 1, end of infusion day 1, and day 2, day 7, day 14, day 30, day 45, day 90, day 120, and day 180 (EOS or ETV) post‐dose] To evaluate the pharmacodynamics (PD) of SAB‐142 in T1D patients following ascending doses in cohorts 1, 2 and 3. ; PD parameters to be evaluated after SAB‐142 administration include: ; ‐ Changes in C‐peptide and HbA1C levels in plasma (T1D patients only). ; This outcome will only be assessed if the T1D cohort dosing proceeds per the specific study criteria.[ Changes in C‐peptide and HbA1C levels in plasma collected via venepuncture pre dose at screening and post dose at day 90 and day 180.] To evaluate the pharmacokinetics (PK) of SAB‐142 in Cohorts 1, 2 and 3 following ascending doses in healthy volunteers. ; PK parameters to be evaluated after SAB‐142 administration include (but are not limited to): ; Plasma ; ‐ Maximum observed concentration (Cmax) ; ‐ Time to Cma X(Tmax) ; ‐ Area under the concentration‐time curve from time 0 to time t (AUC0‐t) ; ‐ Area under the concentration‐time curve from time 0 to the last measurable concentration (AUClast) ; ‐ Half‐life (t1/2) ; ‐ Clearance (Cl) ; ‐ Volume of distribution (Vz) ; ‐ Area under the drug concentration‐time curve from time zero infinity (AUCinf) [ Plasma PK samples will be collected via venepuncture at the following timepoints: within 2 hours pre‐dose on day 1 then 8 hrs post dose on Day 1. PK samples are then collected again post dose at 24hrs, 32hrs, 48hrs, 96hrs then at day 7, day 14, day 30, day 45, day 90 and day 120. ] To evaluate the pharmacokinetics (PK) of SAB‐142 in Cohorts 4 and 5 following ascending doses in healthy volunteers. ; PK parameters to be evaluated after SAB‐142 administration include (but are not limited to): ; Plasma ; ‐ Maximum observed concentration (Cmax) ; ‐ Time to Cma X(Tmax) ; ‐ Area under the concentration‐time curve from time 0 to time t (AUC0‐t) ; ‐ Area under the concentration‐time curve from time 0 to the last measurable concentration (AUClast) ; ‐ Half‐life (t1/2) ; ‐ Clearance (Cl) ; ‐ Volume of distribution (Vz) ; ‐ Area under the drug concentration‐time curve from time zero infinity (AUCinf) [ Plasma PK samples will be collected via venepuncture at the following timepoints: within 2 hours pre‐dose on Day 1 and then 8 hours on Day 1. PK samples are collected within 2 hours pre‐dose on Day 2 and then 8 hours post dose on Day 2. PK samples are then collected again post dose at 48hrs post SOI Day 1 and 96hrs post SOI Day 1 and then at day 7, day 14, day 30, day 45, day 90 and day 120.]