None listed
Conditions
Brief summary
This is a Phase I, randomised, double-blind, placebo-controlled, ascending dose study, with an adaptive patient arm. Healthy volunteers (HVs) and/or patients with Type 1 Diabetes will be enrolled and randomised to 6 cohorts: - Cohort 1: 6 partcipants randomised at a ratio of 2:1 (active: placebo) - Cohorts 2 to 6: 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 4.5 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.
Interventions
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 6 dose levels and is planned to be conducted in healthy volunteers and participants with T1D.
Healthy adult volunteers or T1D patients will be enrolled across a to
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 6 dose levels and is planned to be conducted in healthy volunteers and participants with T1D. Healthy adult volunteers or T1D patients will be enrolled across a total of upto 11 cohorts (6 cohorts + 2 additional cohorts for potential repeated or intermediate dose + up to 3 additional repeat cohorts evaluating the Pharmacodynamic (PD) effects of the new clinical lot of study drug SAB-142): - Cohort 1 (ratio 2:1 active: placebo) - Cohorts 2 to 6 and additional cohorts (8 each cohort, ratio 3:1 active: placebo). The starting dose will be 0.03 mg/kg with 6 dose levels planned (up to 4.5 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 - Cohort 6: 4.5 mg/kg The doses for the 2 repeated or intermediate potential cohorts is yet to be confirmed. The 3 additional repeat PD cohorts will be dosed with dose levels of 0.5 mg/kg, 1.5 mg/kg and/or 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. Participants in Cohort 6 will receive 0.5 mg/kg of SAB-142/placebo on Day 1, 2.0mg/kg on Day 2 and 2.0mg/kg on Day3. The total maximum study duration for participants will be 165 days, which includes a 45-day screening period, 7-day confinement period, and a 113-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 90 and at the end of study (EOS) visit on day 120. 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.
Sponsors
Sab BioTherapeutuics
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 45 Years
Healthy volunteers
Yes
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;
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. History of moderate to severe infusion reaction, or moderate to severe allergic reaction including anaphylaxis; 5. 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); 6. 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; 7. 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; 8. Any skin condition or abnormality at an intended injection site that could interfere with the administration of study drug; 9. Previous exposure to rabbit anti-thymocyte immunoglobulin or horse anti-thymocyte immunoglobulin; 10. 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; 11. 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; 12. 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); 13. A history of more than one herpes zoster episode or herpes zoster at more than one dermatome; 14. A history of any opportunistic infection (e.g. CMV, Pneumocystis carinii, aspergillosis, Clostridium difficile, Klebsiella, etc.); 15. A history of ongoing chronic or recurrent (more than 2 times in one year) infections (e.g. infected indwelling prosthesis, osteomyelitis, chronic sinusitis, others); 16. History of or positive test result for active human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies; 17. History of active, latent or inadequately treated tuberculosis (TB) infection. 18. 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; 19. 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; 20. Any active infection with or without treatment within 30 days prior to screening; 21. History of drug dependence within the last 12 months prior to screening or current substance abuse or drug dependence on any intoxicating substance 22. 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; 23. 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]); 24. History of any malignant disease (excludes surgically resected skin squamous cell or basal cell carcinoma); 25. Positive alcohol breath test upon admission to the clinic on Day -1; 26. Positive urine drugs of abuse test at screening or upon admission to the clinic on Day -1; 27. Participant has a positive cotinine test at screening or upon admission to the clinic on Day -1; 28. 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); 29. 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. 30. 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; 31. Participant is breastfeeding, or pregnant, or planning to breastfeed or become pregnant during the study; 32. 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; 33. 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.
Outcome results
None listed