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Trial registered on ANZCTR


Registration number
ACTRN12622001236785
Ethics application status
Approved
Date submitted
8/09/2022
Date registered
13/09/2022
Date last updated
30/09/2022
Date data sharing statement initially provided
13/09/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Combination immunotherapy for children and young adults with recently-diagnosed type 1 diabetes
Scientific title
Effect of abatacept with or without nasal insulin on beta cell function in children and young adults with recently-diagnosed type 1 diabetes
Secondary ID [1] 307952 0
None
Universal Trial Number (UTN)
U1111-1282-3502
Trial acronym
IAA Trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 1 diabetes 327605 0
Condition category
Condition code
Metabolic and Endocrine 324692 324692 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Abatacept 125mg weekly by subcutaneous injection for 48 doses combined with nasal insulin (100U/mL) dosed as 4x100mcl sprays (2 per nostril) daily for 10 consecutive days, starting on the day of the first abatacept injection, and then on two consecutive days each week for another 46 weeks.
Adherence determined by review of home diary and inspection of returned syringes and spray bottles.
Intervention code [1] 324407 0
Treatment: Drugs
Comparator / control treatment
Abatacept subcutaneous injection combined with nasal placebo (0.9% sodium chloride) administered in the same manner as the active treatment of abatacept and nasal insulin described above.
Control group
Placebo

Outcomes
Primary outcome [1] 332509 0
2-hour C-peptide area under the curve following mixed meal (Resource® Protein Nutritional Drink manufactured by Nestle´ Nutrition; 6ml/kg body weight to a maximum of 360ml), measured using serum samples collected at times -5, 0, 15, 30, 60, 90 and 120 minutes of the meal.
Timepoint [1] 332509 0
48 weeks after first dose of study drugs.
Secondary outcome [1] 413774 0
2-hour C-peptide area under the curve following mixed meal (Resource® Protein Nutritional Drink manufactured by Nestle´ Nutrition; 6ml/kg body weight to a maximum of 360ml), measured using serum samples collected at times -5, 0, 15, 30, 60, 90 and 120 minutes of the meal.
Timepoint [1] 413774 0
24, 72 and 96 weeks after first dose of study drugs.
Secondary outcome [2] 413775 0
Estimated C-peptide AUC according to the equation described by Wentworth et al (Diabetologia; volume 62, p 33–40; 2019). The equation inputs are: body mass index, days since diagnosis of type 1 diabetes, fasting C-peptide, fasting glucose and HbA1c. Body mass index will be calculated from weight obtained from a calibrated scale and height from a stadiometer. C-peptide, fasting C-peptide and fasting glucose will be measured by a NATA-accredited laboratory using a blood sample.
Timepoint [2] 413775 0
-2, 24, 48, 72 and 96 weeks after first dose of study drugs.
Secondary outcome [3] 413776 0
HbA1c measured by NATA-accredited laboratory using a blood sample.
Timepoint [3] 413776 0
0, 12, 24, 36, 48, 60, 72 and 96 weeks after first dose of study drugs.
Secondary outcome [4] 413777 0
Daily insulin dose, determined by reviewing participant diary.
Timepoint [4] 413777 0
-2, 0, 4, 8, 12, 16, 20, 24, 30, 36, 42, 48, 60, 72 and 96 weeks after first dose of study drugs.
Secondary outcome [5] 413779 0
Body weight measured by calibrated electronic scales.
Timepoint [5] 413779 0
0, 12, 24, 48, 60, 72 and 96 weeks after first dose of study drugs.
Secondary outcome [6] 413780 0
Blood pressure measured by sphygmomanometer.
Timepoint [6] 413780 0
0, 12, 24, 48, 60, 72 and 96 weeks after first dose of study drugs.
Secondary outcome [7] 413781 0
Quality of life measures: Problem Areas in Diabetes (PAID) survey.
Timepoint [7] 413781 0
-2, 0, 24, 48, 72 and 96 weeks after first dose of study drugs.
Secondary outcome [8] 413798 0
Quality of life measures: Diabetes Treatment Satisfaction Questionnaire (DTSQ).
Timepoint [8] 413798 0
-2, 0, 24, 48, 72 and 96 weeks after first dose of study drugs.
Secondary outcome [9] 413799 0
Quality of life measures: Hypoglycaemia Fear Survey.
Timepoint [9] 413799 0
-2, 0, 24, 48, 72 and 96 weeks after first dose of study drugs.
Secondary outcome [10] 413800 0
Continuous glucose monitoring percentage time within the range of 3.9 to 10.0 mmol/l
Timepoint [10] 413800 0
-2, 0, 4, 8, 12, 16, 20, 24, 30, 36, 42, 48, 60, 72 and 96 weeks after first dose of study drugs.
Secondary outcome [11] 413801 0
Continuous glucose monitoring percentage time below 3.9 mmol/l
Timepoint [11] 413801 0
-2, 0, 4, 8, 12, 16, 20, 24, 30, 36, 42, 48, 60, 72 and 96 weeks after first dose of study drugs.
Secondary outcome [12] 413802 0
Continuous glucose monitoring percentage time below 3.0 mmol/l
Timepoint [12] 413802 0
-2, 0, 4, 8, 12, 16, 20, 24, 30, 36, 42, 48, 60, 72 and 96 weeks after first dose of study drugs.
Secondary outcome [13] 413803 0
Continuous glucose monitoring mean glucose.
Timepoint [13] 413803 0
-2, 0, 4, 8, 12, 16, 20, 24, 30, 36, 42, 48, 60, 72 and 96 weeks after first dose of study drugs.
Secondary outcome [14] 413804 0
Continuous glucose monitoring glucose coefficient of variation.
Timepoint [14] 413804 0
-2, 0, 4, 8, 12, 16, 20, 24, 30, 36, 42, 48, 60, 72 and 96 weeks after first dose of study drugs.

Eligibility
Key inclusion criteria
Age between 6 and 21 years and weight>20kg at Screening Visit; diabetes mellitus diagnosed within 100 days of first dose of study drugs; presence of at least one islet autoantibody; random C-peptide >0.3nmol/l; using CGM and willing to do this for the duration of the study; demonstrated ability to record home glucose and insulin doses; willing to forego other forms of experimental treatment during the study; up to date with recommended vaccinations; willing to postpone live vaccine immunisations for 3 months after end of treatment.
Minimum age
6 Years
Maximum age
21 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Clinical or laboratory evidence of active infection other than localised skin infection; immunodeficiency or chronic use of immunosuppressive drugs other than topical or inhaled glucocorticoid; vaccination with live or dead virus within 4 weeks of the first dose of study drugs; history of malignancy; pregnant or lactating, or of child-bearing potential not using an effective method of contraception; any pathology of the nasal passages that would contraindicate nasal spray treatment; any condition that would interfere with study conduct or participant safety

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)
Sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation
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
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
For the primary outcome, the comparison between the two treatment arms will be performed by applying the loge(x+1) transformation on the average C-peptide concentration and using a t-test and an ANCOVA model adjusted for gender, baseline age and baseline average C-peptide concentration and with treatment arm as main effect.
For other outcomes, treatment groups will be compared using ANOVA for continuous data and Fisher’s exact test for categorical data, with adjustment for multiple comparisons as appropriate. Mixed-effect multilevel regression analysis will be performed to examine overall longitudinal changes whilst controlling for potential confounders.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/11/2022
Actual
Date of last participant enrolment
Anticipated
31/10/2023
Actual
Date of last data collection
Anticipated
31/10/2025
Actual
Sample size
Target
62
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,WA,VIC
Recruitment hospital [1] 23131 0
Perth Children's Hospital - Nedlands
Recruitment hospital [2] 23132 0
Womens and Childrens Hospital - North Adelaide
Recruitment hospital [3] 23133 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [4] 23134 0
The Royal Childrens Hospital - Parkville
Recruitment hospital [5] 23135 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [6] 23136 0
Queensland Children's Hospital - South Brisbane
Recruitment postcode(s) [1] 38491 0
6009 - Nedlands
Recruitment postcode(s) [2] 38492 0
5006 - North Adelaide
Recruitment postcode(s) [3] 38493 0
2145 - Westmead
Recruitment postcode(s) [4] 38494 0
3052 - Parkville
Recruitment postcode(s) [5] 38495 0
4101 - South Brisbane

Funding & Sponsors
Funding source category [1] 312216 0
Government body
Name [1] 312216 0
NHMRC
Country [1] 312216 0
Australia
Funding source category [2] 312217 0
Charities/Societies/Foundations
Name [2] 312217 0
JDRF
Country [2] 312217 0
United States of America
Primary sponsor type
Government body
Name
Melbourne Health
Address
300 Grattan Street Parkville, Victoria, 3050
Country
Australia
Secondary sponsor category [1] 313746 0
None
Name [1] 313746 0
None
Address [1] 313746 0
None
Country [1] 313746 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311597 0
Melbourne Health Hospital Human Research Ethics Committee
Ethics committee address [1] 311597 0
Ethics committee country [1] 311597 0
Australia
Date submitted for ethics approval [1] 311597 0
22/03/2022
Approval date [1] 311597 0
29/08/2022
Ethics approval number [1] 311597 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 121662 0
A/Prof John Wentworth
Address 121662 0
RMH Department of Diabetes and Endocrinology
300 Grattan Street
Parkville, Vic, 3050
Country 121662 0
Australia
Phone 121662 0
+61 3 93427365
Fax 121662 0
+61 3 93428933
Email 121662 0
john.wentworth@mh.org.au
Contact person for public queries
Name 121663 0
John Wentworth
Address 121663 0
RMH Department of Diabetes and Endocrinology
300 Grattan Street
Parkville, Vic, 3050
Country 121663 0
Australia
Phone 121663 0
+61 3 93427365
Fax 121663 0
+61 3 93428933
Email 121663 0
diabetesendo@mh.org.au
Contact person for scientific queries
Name 121664 0
John Wentworth
Address 121664 0
RMH Department of Diabetes and Endocrinology
300 Grattan Street
Parkville, Vic 3050
Country 121664 0
Australia
Phone 121664 0
+61 3 93427365
Fax 121664 0
+61 3 93428933
Email 121664 0
diabetesendo@mh.org.au

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 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.