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Trial registered on ANZCTR


Registration number
ACTRN12624001043527
Ethics application status
Approved
Date submitted
31/07/2024
Date registered
28/08/2024
Date last updated
28/08/2024
Date data sharing statement initially provided
28/08/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Investigating the safety, tolerability and immune modulation of a novel treatment for stage 3 type one diabetes and help preserve remaining beta cells.
Scientific title
A phase 1, randomised, double-blind, placebo-controlled, single-dose and multi-dose escalation study to investigate the safety, tolerability and pharmacodynamics of subcutaneously administered proinsulin peptide/calcitriol liposomes (ASITI-201) in stage 3 Type 1 Diabetes.
Secondary ID [1] 311553 0
ASITI-24-01-T1D
Universal Trial Number (UTN)
Trial acronym
ASITI-201-T1D
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetes 332914 0
Type one diabetes 332915 0
Metabolic and Endocrine 332916 0
Stage 3 type one diabetes 334045 0
Condition category
Condition code
Metabolic and Endocrine 329628 329628 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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 497 ng/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 0.3 mL subcutaneous injection of ASITI-201 containing 497 ng/mL calcitriol and 13.8 µg/mL proinsulin peptide, or approximately 2.1 ng/kg calcitriol and 0.059 µg/kg proinsulin peptide (4 patients);
• Single 0.3 mL subcutaneous injection of placebo containing sterile 0.9% saline for injection (2 patients).
Dose Level 3
• Single 1 mL subcutaneous injection of ASITI-201 containing 497 ng/mL calcitriol and 13.8 µg/mL proinsulin peptide, or approximately 7.1 ng/kg calcitriol and 0.197 µg/kg proinsulin peptide (4 adult patients);
• Single 1 mL subcutaneous injection of placebo containing sterile 0.9% saline for injection (2 patients)

Part B: The 2 dose levels for the 2 groups in Part B will be determined based on the results of Part A. Part B will commence after 29 days of observation of Part A participants post injection. Dose levels between minimum 0.1 mL and maximum 1 mL will be administered by a research nurse at the hospital site three times weekly doses i.e. 3 weeks
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.
Intervention code [1] 328785 0
Treatment: Drugs
Comparator / control treatment
Single 0.3 mL subcutaneous injection of placebo containing sterile 0.9% saline for injection
Control group
Placebo

Outcomes
Primary outcome [1] 338495 0
To determine the short-term safety of single and multiple doses of ASITI-201 in patients with stage 3 type one diabetes. Composite primary outcome
Timepoint [1] 338495 0
Timepoint 4 hours after first injection, then after each visit at Day 8, Day 15 and D29 for part A,
Timepoint 4 hours after first injection, then after each dose at Day 8 and Day 15, and at each visit at week 4, 12 and 24 for part B.
Secondary outcome [1] 436151 0
To monitor pharmacokinetics of calcitriol in plasma before and after first dose of ASITI-201.
Timepoint [1] 436151 0
pre-dose and at 1, 2 and 4 hours post administration of IMP in parts A and B.
Secondary outcome [2] 436152 0
To assess the effect of ASITI-201 relative to placebo on mechanistic outcomes
Timepoint [2] 436152 0
Timepoint 8 hours post administration after first injection, then after each Day 8, Day 15 and Day 29 for part A.
Secondary outcome [3] 436153 0
To evaluate ß cell function after ASITI administration relative to placebo for Part B before and 6 months post dose 1 for Part B.
Timepoint [3] 436153 0
2-hour post mixed meal completion before and 6 months post dose 1.
Secondary outcome [4] 436155 0
To evaluate the change in random C-peptide and stimulated C-peptide AUC over 24 weeks. This will be assessed as a composite outcome.
Timepoint [4] 436155 0
Timepoint 8 hours post administration after first injection, then after each Day 8, Day 15 and Day 29 for part A and Day 8, Day 15, Day 29, week 12 and week 24 for Part B..
Secondary outcome [5] 439084 0
To assess the effect of ASITI-201 relative to placebo on mechanistic outcomes
Timepoint [5] 439084 0
Timepoint 8 hours post administration after first injection, then after each visit at Day 8, Day 15 and Day 29 for part A.
Secondary outcome [6] 439085 0
To assess the effect of ASITI-201 relative to placebo on mechanistic outcomes
Timepoint [6] 439085 0
Timepoint 8 hours post administration after first injection, then after each visit at Day 8, Day 15 and Day 29 for part A.
Secondary outcome [7] 439086 0
To assess the effect of ASITI-201 relative to placebo on mechanistic outcomes
Timepoint [7] 439086 0
Timepoint 8 hours post administration after first injection, then after each visit at Day 8, Day 15 and Day 29 for part A.

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
45 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

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)
central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
simple randomisation using a randomisation tablet created by computer software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
No formal sample size calculations were performed for this study. This is a conventional phase 1 design to assess the relationship between dose and the primary and secondary endpoints. Analyses of outcomes will be conducted on both Per Protocol (PP) intention-to-treat (ITT) basis. Results for both ITT and PP analyses will be reported separately.

Per Protocol (PP) Population
The PP population will include all randomised participants who fully adhere to the study protocol, i.e, receiving study drug who are compliant with inclusion/exclusion criteria, study drug administration, study procedures, and measurement follow-up.

Intention to Treat (ITT) Population
The ITT population will include all participants who are randomised into the study, regardless of adherence to the study protocol, compliance with the treatment, or completion of the study. Participants will be analysed according to the group to which they were originally assigned.

Safety Analysis Set
The safety analysis set will include all participants who receive at least one injection of study drug. Participants will be included in the treatment group according to the actual treatment received regardless of their randomised assignment.

Per Protocol (PP) Analysis
This will be the primary analysis set. Only participants who complete the study per the protocol without major deviations will be included in the PP analysis.

For these analyses:
• Descriptive statistics will be used to summarise baseline characteristics of the PP population.
• Summary statistics of secondary and exploratory endpoints will be tabulated
• The secondary efficacy endpoint will be analysed using linear regression.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
28/08/2024
Actual
Date of last participant enrolment
Anticipated
31/05/2025
Actual
Date of last data collection
Anticipated
30/11/2025
Actual
Sample size
Target
36
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 26669 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 42709 0
4102 - Woolloongabba

Funding & Sponsors
Funding source category [1] 315848 0
Government body
Name [1] 315848 0
Australia Government Department of Health and Aged Care: Medical Research Commercialisation Fund
Country [1] 315848 0
Australia
Funding source category [2] 316707 0
Charities/Societies/Foundations
Name [2] 316707 0
JDRF
Country [2] 316707 0
Australia
Primary sponsor type
University
Name
UniQuest Pty Ltd
Address
Country
Australia
Secondary sponsor category [1] 318909 0
None
Name [1] 318909 0
None
Address [1] 318909 0
Country [1] 318909 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314704 0
Metro South Human Research Ethics Committee
Ethics committee address [1] 314704 0
https://metrosouth.health.qld.gov.au/research/about-us/hrec
Ethics committee country [1] 314704 0
Australia
Date submitted for ethics approval [1] 314704 0
31/05/2024
Approval date [1] 314704 0
12/07/2024
Ethics approval number [1] 314704 0
HREC/2024/QMS/107946

Summary
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, where after dose finding in Part A, Part B will commence. Part A is a randomised double blind, placebo-controlled, single centre, single-dose escalation study. Up to 18 eligible participants will be randomised into Part A of the study and three dose levels will be assessed in a single dose escalation. Part B is a randomised double blind, placebo-controlled, multi centre, multiple-dose escalation study. Up to 18 eligible participants will be randomised into Part B and the dose levels to be tested will be based upon review of aggregated data for safety by the Safety Monitoring Committee and immunomodulatory effects by the statistician for all dose levels tested in Part A.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 132454 0
Dr Aakansha Zala
Address 132454 0
The Princess Alexandra Hospital, 199 Ipswich Rd, Woolloongabba QLD 4102
Country 132454 0
Australia
Phone 132454 0
+61 7 3443 6956
Fax 132454 0
Email 132454 0
[email protected]
Contact person for public queries
Name 132455 0
Michelle Roch
Address 132455 0
The Frazer Institute (The University of Queensland) 37 Kent Street, Woolloongabba QLD 4102
Country 132455 0
Australia
Phone 132455 0
+61 73443 6956
Fax 132455 0
Email 132455 0
[email protected]
Contact person for scientific queries
Name 132456 0
Aakansha Zala
Address 132456 0
The Princess Alexandra Hospital, 199 Ipswich Rd, Woolloongabba QLD 4102
Country 132456 0
Australia
Phone 132456 0
+61 73443 6956
Fax 132456 0
Email 132456 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
the data will be aggregated.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.