None listed
Conditions
Brief summary
This Phase 1 clinical trial will test the hypothesis that co-delivery of calcitriol with PI33-63 self-antigen in a liposome is safe and promotes antigen-specific immune regulation in adult patients with Stage 3 type one diabetes. The study is in two parts, Part A is complete and Part B is now recruiting. Part A was a randomised double blind, placebo-controlled, single centre, single-dose escalation study. Up to 18 eligible participants were randomised, and three dose levels were evaluated in a single dose escalation. Part A is now complete. Part B is a randomised double blind, placebo-controlled, multiple-dose escalation study. Up to 18 eligible participants will be randomised. The two dose levels to be tested (0.2 mL and 0.4 ml) were approved by the Safety Monitoring Committee based on safety and immunomodulatory effects assessed by the unblinded statistician for all dose levels tested in Part A.
Interventions
ASITI-201 will be administered subcutaneously by a research nurse in a single-dose escalation and multiple dose, dose-ranging parallel group study in two parts.
Part A: Three dose levels will be assessed in a single dose escalation study design Participants will be assigned to a dose level and s.c. site administration will be monitored.
Dose Level 1 (4 active, 2 placebo)
Dose Level 2 (4 active, 2 placebo)
Dose Level 3 (4 active, 2 placebo)
At each dose level two sentinel participants (1 active,
ASITI-201 will be administered subcutaneously by a research nurse in a single-dose escalation and multiple dose, dose-ranging parallel group study in two parts. Part A: Three dose levels will be assessed in a single dose escalation study design Participants will be assigned to a dose level and s.c. site administration will be monitored. Dose Level 1 (4 active, 2 placebo) Dose Level 2 (4 active, 2 placebo) Dose Level 3 (4 active, 2 placebo) At each dose level two sentinel participants (1 active, 1 placebo) will be initially randomised. Dose Level 1 • Single 0.1 mL subcutaneous injection of ASITI-201 containing 0.5 µg/mL calcitriol and 13.8µg/mL proinsulin peptide, or approximately 0.7 ng/kg calcitriol and 0.020 µg/kg proinsulin peptide (4 patients); • Single 0.1 mL subcutaneous injection of placebo containing sterile 0.9% saline for injection (2 patients). Dose Level 2 • Single 0.2 mL subcutaneous injection of ASITI-201 containing 0.5 µg/mL calcitriol and 13.8 µg/mL proinsulin peptide, or approximately 1.4 ng/kg calcitriol and 0.04 µg/kg proinsulin peptide (4 patients); • Single 0.2 mL subcutaneous injection of placebo containing sterile 0.9% saline for injection (2 patients). Dose Level 3 • Single between 0.05 mL to 1 mL subcutaneous injection of ASITI-201 containing 0.5 µg/mL calcitriol and 13.8 µg/mL proinsulin peptide, or approximately 0.4 to 7.1 ng/kg calcitriol and 0.01 to 0.20 µg/kg proinsulin peptide (4 adult patients); • Single equivalent volume subcutaneous injection of placebo containing sterile 0.9% saline for injection (2 patients) Part B: Study participants will receive three administrations of IMP at weekly intervals (Day 1, Day 8, Day 15). There will be two patient cohorts and each of these groups will receive a different dose level of ASITI-201. Six patients in each cohort will receive subcutaneous ASITI-201 and 3 patients will receive placebo. Final dose selection will be based upon results from Parts A of the study with pre-defined selection criteria by the SMC and Dose Monitoring Team. Dose Group 1 (6 active, 3 placebo) Dose Group 2 (6 active, 3 placebo). The 2 dose levels to be tested in Part B will be based upon review of results in Part A. Subcutaneous site injection will be monitored.
Sponsors
UniQuest Pty Ltd
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver)
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
1. Adults who meet the American Diabetes Association T1D criteria; Female of child-bearing potential must agree to use two effective forms of contraception from enrolment to completion of the study 2. Diagnosis of T1D within 5 years of enrolment; 3. Positive for at least one diabetes-related autoantibody, including but not limited to: Glutamate decarboxylase-65 (GAD-65); Insulin, if obtained within 10 days of the onset of exogenous insulin therapy; Insulinoma antigen-2 (IA-2); or Zinc transporter-8 (ZnT8); 4. Random C-peptide >0.2 nmol/L or MMTT-stimulated mean C-peptide AUC of >0.2 nmol/L; 5. Positive for HLA-DQB1*03:02 or HLA-DQB1*02:01; 6. Written informed consent; 7. Agree to forego vaccinations during the first 4 weeks of the study.
Exclusion criteria
1. Latent autoimmune diabetes of adults (LADA) 2. History of malignancy or serious uncontrolled cardiovascular, nervous system, pulmonary, renal, liver or gastrointestinal disease. 3. An active inflammatory disease other than T1D with the exception of stable thyroid or celiac disease; 4. Current or prior treatment that is known to cause a significant, ongoing change in the course of T1D or immunologic status e.g. including Teplizumab, TNF inhibitors or JAK inhibitors. 5. Current use of drugs other than insulin to treat hyperglycaemia (e.g. metformin, sulfonylureas, glinides, thiazolidinedione, GLP1 agonists, SGLT2 inhibitors, DPP-IV inhibitors, or amylin). 6. Current use of any medication known to significantly influence glucose tolerance (e.g., atypical antipsychotics, diphenylhydantoin, niacin, systemic glucocorticoids, beta blockers). 7. Serious infection requiring hospitalisation within last 28 days; 8. Receipt of any live attenuated vaccines within 4 weeks prior to entry; 9. Major surgery within last 28 days; 10. CBC, haemoglobin, platelets, creatinine, bilirubin, and AST/ALT greater than 1.5 x out of normal laboratory ranges at entry 11. Positive serology for HIV, or infection with HBV or HCV; 12. Any known or suspected allergies to the study drug or its constituents or a history of severe allergy or anaphylaxis; 13. Inadequate venous access to allow collection of blood samples; 14. History of drug or alcohol abuse; 15. Participation in any other clinical trial of an investigational medical product or device within 30 days or 5 half-lives before study start, whichever comes later; 16. If, in the opinion of the PI, the participant appears not to be able to perform the needed responsibilities of participation in the clinical study.
Outcome results
None listed