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
- Conditions
- Type 1 diabetesMetabolic and Endocrine - DiabetesInflammatory and Immune System - Autoimmune diseases
- Registration Number
- ACTRN12623001089628
- Lead Sponsor
- Sab BioTherapeutuics
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 78
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
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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method