Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623001089628
Ethics application status
Approved
Date submitted
31/08/2023
Date registered
17/10/2023
Date last updated
13/04/2024
Date data sharing statement initially provided
17/10/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
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
Scientific title
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 in Healthy Volunteers and participants with Type 1 Diabetes (T1D).
Secondary ID [1] 310336 0
SAB-142-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 1 diabetes 331067 0
Condition category
Condition code
Metabolic and Endocrine 327858 327858 0 0
Diabetes
Inflammatory and Immune System 328059 328059 0 0
Autoimmune diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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 cohort, or will be equivalent to the last dose level administered to the HVs if a transition to the T1D patients is recommended after the sentinel dosing.

Dosing in each cohort will commence with two sentinel participants, with one of the two sentinels randomised to receive SAB-142 and the other randomised to receive placebo. The sentinel participants will be monitored in the clinic for at least 7 days and at least 3 days of available safety/tolerability data (including blood and urine safety laboratory results) will be reviewed by the Safety Review Committee (SRC) prior to dosing the remainder of participants in each cohort.

SAB-142 or placebo will be diluted to the appropriate dose level in 500 mL of 0.9% sodium chloride by the unblinded study pharmacist. Intravenous infusion of study drug will be over approximately 8 hours. Participants in Cohorts 1 through to 3 will be administered the complete dose of study drug (up to 0.5 mg/kg) on Day 1. Participants in Cohorts 4 and 5 will be administered 0.5 mg/kg of study drug on Day 1 with the remaining dose with an additional 500 mL of 0.9% sodium chloride on Day 2.

The total maximum study duration for participants will be 232 days, which includes a 45-day screening period, 7-day confinement period, and a 173-day follow-up period.

Participants will be required to attend the study clinic at the 2 screening visits and at follow-up visits on Day 10, day 14, day 30, day 45, day 60, day 90, day 120 and at the end of study (EOS) visit on day 180. Participants will be confined to the clinical facility from Day -1 to Day 7 (a total of 7 nights and 8 days)

Clinical facility staff will administer the study drug only to participants included in this study following the procedures set out in this study protocol. Administration of study drugs will be recorded in the appropriate drug accountability records and the eCRF. Administration of study drug will be verified by a second staff member. Each participant will be given only the study drug preparation carrying his/her study number.
Intervention code [1] 326736 0
Treatment: Drugs
Comparator / control treatment
Placebo (commercially available sterile Saline solution 0.9%) will be indentical in appearance to the study drug and will be administered via intravenous infusion.
Control group
Placebo

Outcomes
Primary outcome [1] 335703 0
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)
Timepoint [1] 335703 0
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).
Primary outcome [2] 335733 0
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)
Timepoint [2] 335733 0
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).
Secondary outcome [1] 425240 0
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 Cmax (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)
Timepoint [1] 425240 0
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.
Secondary outcome [2] 425393 0
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 Cmax (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)
Timepoint [2] 425393 0
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.
Secondary outcome [3] 425395 0
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
Timepoint [3] 425395 0
- 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
Secondary outcome [4] 425398 0
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
Timepoint [4] 425398 0
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).
Secondary outcome [5] 427262 0
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.
Timepoint [5] 427262 0
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.

Eligibility
Key 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 index (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 and at check in on Day -1, including:
a. Physical examination without any clinically relevant findings;
b. No history of usual and/or multiple occasions of systolic blood pressure (BP) less than or equal to 95 mmHg;
c. Systolic BP in the range of 95 to 140 mmHg and diastolic BP in the range of 40 to 90 mmHg after 5 minutes in semi-supine position, measured on 3 occasions prior to randomisation (2 at the screening visit and on Day -1)
d. Heart rate (HR) in the range of 45 to 100 beats per minute (bpm) after 5 minutes rest in supine or semi-supine position measured on 3 occasions prior to randomisation (2 at the screening visit and on Day -1).
e. Tympanic temperature, between 35.5°C and 37.5°C, inclusive;
f. No clinically significant findings in serum chemistry, haematology, coagulation or urinalysis tests as judged by the PI (or delegate);
g. ECG without clinically significant abnormality including at screening, check-in Day -1, and pre-dose on Day 1, as determined by the investigator including intraventricular conduction delays (QRS interval greater than or equal to 120msec or PR interval greater than or equal to 220msec in individuals with a heart rate less than 70 beats per minute) and resting QT interval corrected for Fredericia (QTcF) less than or equal to 450msec for both male and female subjects;
h. No history or current signs and symptoms of autoimmune disorders for HVs. For T1D patients, no uncontrolled autoimmune disorders (T1D and comorbid autoimmune conditions such as autoimmune thyroiditis or celiac disease must be well controlled for the previous 6 months from Screening);
5. Participant is willing to refrain from consuming food or beverages containing caffeine and/or xanthene products, within 24 hours prior to check-in on Day -1.
6. Female participants must be of non-child-bearing potential i.e., surgically sterilised (hysterectomy, bilateral salpingectomy, bilateral oophorectomy at least 6 weeks before the screening visit) or postmenopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause and a follicle stimulating hormone [FSH] level consistent with postmenopausal status, per local laboratory guidelines). Females receiving hormone replacement therapy (HRT) may be considered for inclusion if the need for HRT is for no other medical reason than to treat symptoms associated with menopause. If female participants are of child-bearing potential:
a. Must have a negative pregnancy test at the screening visit and on Day -1. Note that urine test may be performed as an alternative to serum test. If the urine test is positive, pregnancy must be confirmed by a serum test;
b. Must agree not to donate ova or attempt to become pregnant from pre-dose on Day -1 and for the duration of the study;
c. If not exclusively in a same-sex relationship or abstinent as a committed lifestyle, must agree to use adequate contraception (which is defined as use of a condom by the male partner combined with use of a highly effective method of contraception from 1 month prior to first study drug administration for the duration of the study.
7. Male participants must:
a. Agree not to donate sperm from the time of pre-dose on Day 1 and for the duration of the study;
b. If engaging in sexual intercourse with a female partner who could become pregnant, must agree to use adequate contraception (defined as use of a condom plus a highly effective method of contraception from signing the consent form until at least 90 days after the last dose of study drug;
c. If engaging in sexual intercourse with a female partner who is not of childbearing potential, must agree to use a condom from the time of pre-dose on Day 1 and for the duration of the study.
8. All participants must be cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) polymerase-chain reaction (PCR)-negative within 45 days of randomisation and may not have had signs or symptoms of a CMV or EBV-compatible illness lasting longer than 7 days within 45 days of randomisation;
9. Be ‘social smokers’ (1 or 2 occasions in the 3 months prior to first study drug administration) or non-smokers (including tobacco, e-cigarettes, marijuana, cannabis-derived chemical (CBD), or other drugs). All volunteers must agree to refrain from smoking at least 7 days prior to admission to the clinic (Day -1), as confirmed by a negative test for cotinine at check-in on Day -1;
10. Have suitable venous access for blood sampling and Intravenous infusion;
11. Willing and able to comply with all study assessments and adhere to the protocol schedule and restrictions.

Type 1 Diabetic Patients
Stable T1D patients will be included in the study if they satisfy all of the above criteria for HVs and the following criteria:
1. Adult male and females with stable T1D defined as.
a. Type 2 diabetes (T2D) has been excluded;
b. b. Confirmed (electronic or paper medical records, letter from general practitioner or specialist) onset of T1D less than or equal to 5 years;
c. c. T1D and other comorbid autoimmune disorders must be well-controlled within the last 6 months prior to screening;
Minimum age
18 Years
Maximum age
45 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Healthy volunteers and TID patients will be excluded from the study if there is evidence of any of the following at screening or Day -1:
1. History of immunodeficiency or clinically significant chronic lymphopaenia: leukoepaenia; neutropaenia; lymphopaenia, or thrombocytopaenia;
2, History of acute metabolic emergency or other T1D-related events requiring emergency medical service or healthcare professional intervention/Emergency Department visit/hospitalisation within 6 months prior to screening (T1D patients only);
3. Lymphocytes are < 1.25 times the lower limit of normal (LLN) laboratory range on 2 out of 3 (2 screening visits and Day -1 check-in visit) haematology blood draws prior to randomisation;
4. High-sensitivity C-reactive protein (hsCRP) above upper limit of normal range on 2 blood draws prior to randomisation;
5. History of moderate to severe infusion reaction, or moderate to severe allergic reaction including anaphylaxis;
6. Known allergy, hypersensitivity or moderate to severe allergic reaction including anaphylaxis to natural or recombinant antibodies, passive vaccines, or any other component of the study drug formulation (including biologic medications or beef, dairy and gelatin products);
7. Known allergic reactions to the required pre-medication (acetaminophen/paracetamol, methylprednisolone or diphenhydramine) including skin hypersensitivity reaction, moderate to severe hypersensitivity reactions including anaphylaxis, or dizziness;
8. The participant had a loss of more than 500mL blood (e.g. blood donation or participation in a clinical trial) within 1 month before randomisation, or had received any blood, plasma, or platelet transfusion within 3 months before Day-1 check in, or plans to donate blood during the study;
9. Any skin condition or abnormality at an intended injection site that could interfere with the administration of study drug;
10. Previous exposure to rabbit anti-thymocyte immunoglobulin or horse anti-thymocyte immunoglobulin;
11. Receipt of any immunoglobulin or biologic drug such as monoclonal antibodies within 90 days or 5 half-lives (whichever is longer) of the last dose of the drug or receipt of any systemic or high potency topical immunomodulatory or immunosuppressive drug within 1 year from Screening;
12. For HVs: History or presence of any clinically relevant disorder, including cardiovascular (including unstable angina, myocardial infarction, chronic heart failure), haematologic, pulmonary (with the exception of fully resolved childhood asthma), hepatic, renal, gastrointestinal (with the exception of fully resolved childhood food allergies), connective tissue disease, uncontrolled endocrine/metabolic, oncologic (excludes surgically resected skin squamous cell or basal cell carcinoma), neurologic, and psychiatric diseases, or any disorder that may prevent the accurate assessment of the short and long-term safety profile of the investigational drug, successful completion of the study or influence the absorption, distribution, metabolism, excretion, or action of the study drug. For T1D patients: T1D and its comorbidities are not in stable state and/or may prevent the accurate assessment of the short and long-term safety profile of the investigational drug, successful completion of the study, and safe patient participation in the study;
13. Participants with a personal or family history of arrhythmia (at the PI’s discretion), sudden unexplained death at a young age (before 40 years) in a first-degree relative, short or long QT syndrome, or a personal history of syncope within the 4 weeks prior to Screening, or treatment for high blood pressure (medications only);
14. A history of more than one herpes zoster episode or herpes zoster at more than one dermatome;
15. A history of any opportunistic infection (e.g. CMV, Pneumocystis carinii, aspergillosis, Clostridium difficile, Klebsiella, etc.);
16. A history of ongoing chronic or recurrent (more than 2 times in one year) infections (e.g. infected indwelling prosthesis, osteomyelitis, chronic sinusitis, others);
17. History of or positive test result for active human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies;
18. History of active, latent or inadequately treated tuberculosis (TB) infection.
19. Presence or having sequelae of gastrointestinal, liver, kidney, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs excluding cholecystectomy;
20. Use of any vaccine or any prescription medication within 14 days prior to dosing, or use of over-the-counter medication/vitamins/supplements within 7 days prior to planned first dose of study drug. Exceptions include contraception and occasional paracetamol (up to a maximum of 2 g per day), sand for T1D patients, a stable dose of any medications used to manage the disease and its comorbidities (e.g., insulin). Use of St. John’s Wort (hypericin) may not be taken within 30 days prior to planned first dose of study drug. Other medications may be permissible on a case-by-case basis with approval of Sponsor;
21. Any active infection with or without treatment within 30 days prior to screening;
22. History of drug dependence within the last 12 months prior to screening or current substance abuse or drug dependence on any intoxicating substance
23. History or current medical, psychological, or social conditions that, in the opinion of the PI (or delegate), may interfere with the participants inclusion in the clinical study or evaluation of the clinical study results;
24. History of alcohol dependence within the last 12 months prior to screening and/or regular consumption of greater than 14 standard alcoholic drinks/week for females and greater than 21 standard alcoholic drinks/week for males, where 1 standard drink is 10 g of pure alcohol and is equivalent to 285 mL beer [4.9 percent Alc/Vol], 100 mL wine [12 percent Alc/Vol], 30 mL spirit [40 percent Alc/Vol]);
25. History of any malignant disease (excludes surgically resected skin squamous cell or basal cell carcinoma);
26. Positive alcohol breath test upon admission to the clinic on Day -1;
27. Positive urine drugs of abuse test at screening or upon admission to the clinic on Day -1;
28. Participant has a positive cotinine test at screening or upon admission to the clinic on Day -1;
29. Laboratory results at screening that indicate inadequate renal function (estimated creatinine clearance of less than 60 mL/min calculated by the Cockcroft and Gault formula);
30. Liver function test results elevated above the upper limit of normal (ULN) for gamma glutamyl transferase (GGT), ALP, AST or ALT, or total bilirubin; A repeat test is allowed, with 1 of the 2 values being in range.
31. Any abnormality in serum chemistry, haematology, coagulation, or urinalysis at screening and/or at check-in on Day -1 that is outside of the laboratory reference range and considered clinically significant or potentially indicative of infection, inflammation, coagulopathies, liver and/or renal dysfunction by the Investigator and that, in the opinion of the Investigator, could interfere with the objective of the study. Any laboratory abnormality may be re-tested and a participant may be enrolled at the discretion of the PI (or delegate) if any conditions above are excluded;
32. Participant is breastfeeding, or pregnant, or planning to breastfeed or become pregnant during the study;
33. Treatment with a small molecule investigational drug or an investigational vaccine (including those drugs and vaccines used under Emergency Use Authorisation) or a participation in another clinical trial within 30 days or 5 half- lives from the last dose (whichever is longer) prior to the first administration of study drug in this trial or at any time through the study up to the EoS visit;
34. Any other condition or prior therapy that in the opinion of the PI would make the volunteer unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance with any study requirements.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
All study participants who sign an informed consent form (ICF) at screening will receive a unique sequential number (i.e., a screening number). Participants who meet the study eligibility criteria will be assigned a randomisation number pre-dose on Day 1, which corresponds to a study treatment (SAB-142 or placebo).

The randomisation schedule will be prepared by an unblinded statistician and maintained under controlled access. A copy of the randomisation schedule will be provided to unblinded site staff responsible for dispensing the study drugs. The unblinded site staff will store the randomisation schedule in a secure, restricted access area. The unblinded site staff involved in the dispensing of the study drugs will be accountable for ensuring compliance to the randomisation schedule.

Where code-break envelopes are used a record, including date, time, name and signature of the person opening the envelope and reason, must be made both on the opened envelope and in the participant’s medical records
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The allocation to SAB-142 or placebo will be performed using a block randomisation algorithm and will be documented in the study randomisation schedule. Randomisation numbers assigned will be in accordance with this randomisation schedule.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
This study is the FIH study with SAB-142 and as such no formal sample size calculation was performed. The chosen sample size chosen is deemed adequate to evaluate all study endpoints.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
23/11/2023
Actual
28/11/2023
Date of last participant enrolment
Anticipated
1/06/2024
Actual
Date of last data collection
Anticipated
1/12/2024
Actual
Sample size
Target
38
Accrual to date
6
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 25469 0
Nucleus Network Brisbane Clinic - Herston
Recruitment postcode(s) [1] 41277 0
4006 - Herston

Funding & Sponsors
Funding source category [1] 314542 0
Commercial sector/Industry
Name [1] 314542 0
Sab BioTherapeutics
Country [1] 314542 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Sab BioTherapeutuics
Address
40 City Road, Southbank, Victoria, 3006
Country
Australia
Secondary sponsor category [1] 316497 0
Commercial sector/Industry
Name [1] 316497 0
Avance Clinical
Address [1] 316497 0
213 Glynburn Road, Firle, South Australia, 5070
Country [1] 316497 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313583 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 313583 0
55 Commercial Rd, Melbourne VIC 3004
Ethics committee country [1] 313583 0
Australia
Date submitted for ethics approval [1] 313583 0
06/09/2023
Approval date [1] 313583 0
01/10/2023
Ethics approval number [1] 313583 0
540/23 (HREC/101827-Alfred-2023)

Summary
Brief summary
This is a Phase I, randomised, double-blind, placebo-controlled, ascending dose study, with an adaptive patient arm. Healthy volunteers (HVs) will be enrolled and randomised to 5 cohorts:
- Cohort 1: 6 partcipants randomised at a ratio of 2:1 (active: placebo)
- Cohorts 2 to 5: 8 participants in each cohort at a ratio of 3:1 (active: placebo).

SAB-142 is currently being developed as a disease-modifying therapeutic agent to delay the onset and progression of T1D. The purpose of this study is to test the safety of SAB-142 when given to healthy volunteers or Type 1 diabetes patients.

The starting dose will be 0.03 mg/kg with 5 dose levels planned (up to 2.5 mg/kg). Dosing in each cohort will commence with two sentinel participants, with one of the two sentinels randomised to receive SAB-142 and the other randomised to receive placebo. The sentinel participants will be monitored in the clinic for at least 7 days and at least 3 days of available safety/tolerability data will be reviewed by the Safety Review Committee (SRC) prior to dosing the remainder of participants in each cohort.

In the event that adaptive design criteria are met, dosing of HVs will cease, and the study will transition to an adaptive T1D patient part of the study. In this case, T1D patients will be enrolled and randomised (6 participants in each cohort, ratio 2:1 active: placebo). The starting dose for the T1D patients will be equivalent to the next dose level from the last dose administered to the HVs full cohort, or will be equivalent to the last dose level administered to the HVs if a transition to the T1D patients is recommended after the sentinel cohort.

The decision to escalate between dose levels and proceed to the next cohort in HVs or to move to the adaptive T1D patient arm of the study, will be made by the SRC following review of available safety and tolerability data from Day 1 up to Day 14 for all participants in the cohort.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 128638 0
Dr Kristi McLendon
Address 128638 0
Level 5 Clive Berghofer Cancer Centre Research Centre, 300 Herston Road, Herston, QLD 4006
Country 128638 0
Australia
Phone 128638 0
+61 7 3845 3620
Fax 128638 0
Email 128638 0
k.mclendon@nucleusnetwork.com.au
Contact person for public queries
Name 128639 0
Dr Nucleus Network Brisbane
Address 128639 0
Level 5 Clive Berghofer Cancer Centre Research Centre, 300 Herston Road, Herston, QLD 4006
Country 128639 0
Australia
Phone 128639 0
+61 1800 243 733
Fax 128639 0
Email 128639 0
brisbane@nucleusnetwork.com
Contact person for scientific queries
Name 128640 0
Dr Tom Luke
Address 128640 0
SAB Biotherapeutics, Inc. 2100 East 54th Street. N Sioux Falls, South Dakota, 57104
Country 128640 0
United States of America
Phone 128640 0
+1 605 377 6027
Fax 128640 0
Email 128640 0
tluke@sab.bio

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
No Results