Insulin and Abatacept in Recently-diagnosed Type 1 Diabetes (IAA)

Abatacept Combined With Nasal Insulin to Preserve Beta-cell Function in Recently-diagnosed Type 1 Diabetes

The goal of this clinical trial is to test whether the combination of two safe immune therapies called abatacept and nasal insulin can preserve pancreas function in recently-diagnosed type 1 diabetes. When type 1 diabetes is first diagnosed, the pancreas is still able to make small amounts of insulin, which helps control glucose levels. Preserving pancreas function can make glucose control easier and reduce the need to use injected insulin.

Participants will be asked to inject abatacept under their skin once per week and inhale nasal insulin or nasal placebo using a spray for 10 consecutive days initially and twice per week thereafter. The treatment period is for 48 weeks, with another 48-week follow-up period.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 1; Type 1 Diabetes
• Intervention / Treatment: Drug: Abatacept (CTLA4-Ig) and nasal insulin (Humulin R®); Drug: Abatacept (CTLA4-Ig) and nasal placebo (0.9% sodium chloride)

Detailed Description

Type 1 diabetes is caused by an immune attack on insulin-producing beta cells of the pancreas that impairs their ability to make insulin to control blood glucose levels. When diabetes is diagnosed, the pancreas is usually still able to make some insulin, but not enough to meet the body's needs. Over time, continued immune attack further decreases insulin production until after one to two years it is very low or undetectable. When type 1 diabetes is diagnosed, treatments that stop the immune attack may preserve residual beta-cell function. This decreases the requirement for injected insulin and improves glucose control. However, so far, immune therapies have not been shown to prevent ongoing loss of beta-cell function. In this clinical trial, two safe immune therapies called abatacept and nasal insulin will be used together to test if the combination can better preserve the function of beta cells to make insulin after diagnosis. If this occurs, it will be relatively simple to develop this treatment for routine use in recently-diagnosed people and to test whether it prevents high-risk individuals progressing to need insulin injections. This trial will also provide research samples to improve our understanding of how type 1 diabetes develops and how abatacept and nasal insulin might affect this process. The new knowledge created from studying these samples will improve our ability to use abatacept and nasal insulin to preserve pancreas function in type 1 diabetes.

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • The Children's Hospital at Westmead
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Queensland Children's Hospital
  • South Australia
    • North Adelaide, South Australia, Australia, 5006
      • Women's and Children's Hospital
  • Victoria
    • Parkville, Victoria, Australia, 3050
      • The Royal Melbourne Hospital
    • Parkville, Victoria, Australia, 3052
      • The Royal Children's Hospital
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Perth Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age between 6 and 21 years and weight at least 20kg at Visit 1
• Diabetes mellitus diagnosed according to ADA criteria (53) within 100 days of Visit 2
• Presence of at least one antibody against insulin (if <10 days since starting insulin therapy), GAD, IA2 or ZnT8
• Random C-peptide >0.3nmol/l, measured by a NATA-accredited pathology laboratory within 2 weeks of Visit 2
• Willing to use CGM for the duration of the study
• Demonstrated ability to record home glucose measurements and insulin doses, as judged by the study doctor
• Willing to forego other forms of experimental treatment during the study
• Fully vaccinated against Covid-19, as recommended by the Australian Technical Advisory Group on Immunisation
• Up to date with other vaccinations recommended by the Australian Technical Advisory Group on Immunisation
• Willing to postpone any live vaccine immunisations for 3 months after treatment

Exclusion Criteria:

• Clinical or laboratory evidence of active infection other than localised skin infection, including viral hepatitis, EBV, CMV or tuberculosis
• Immunodeficiency or chronic use of immunosuppressive drugs other than topical or inhaled glucocorticoid
• Vaccination with live or dead virus within 4 weeks of Visit 2
• 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 preclude safe application of the nasal spray
• Any condition that would interfere with study conduct or participant safety

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Abatacept and nasal insulin; Abatacept (CTLA4-Ig; 50 mg for participant weight <25 kg, 87.5 mg for participant weight 25-50 kg, 125 mg for participant weight >50 kg) will be injected subcutaneously once per week and nasal insulin (Humulin R®, 100 Units/mL) will be inhaled for 10 consecutive days initially and twice per week thereafter, for 48-weeks.	Drug: Abatacept (CTLA4-Ig) and nasal insulin (Humulin R®); Abatacept injected subcutaneously once per week and nasal insulin inhaled for 10 consecutive days initially and twice per week thereafter; Other Names: Abatacept and nasal insulin
Placebo Comparator: Abatacept and nasal placebo; Abatacept (CTLA4-Ig; 50 mg for participant weight <25 kg, 87.5 mg for participant weight 25-50 kg, 125 mg for participant weight >50 kg) will be injected subcutaneously once per week and nasal placebo (0.9% sodium chloride) will be inhaled for 10 consecutive days initially and twice per week thereafter, for 48-weeks.	Drug: Abatacept (CTLA4-Ig) and nasal placebo (0.9% sodium chloride); Abatacept injected subcutaneously once per week and nasal placebo inhaled for 10 consecutive days initially and twice per week thereafter; Other Names: Abatacept and nasal placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Beta-cell function at 48 weeks	Change in average C-peptide concentration during a 2-hour mixed meal challenge	0 weeks - 48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Beta-cell function at 24, 72 and 96 weeks	Change in average C-peptide concentration during a 2-hour mixed meal challenge	0, 24, 72 and 96 weeks
Glucose regulation	Proportion of time in the range 3.9-10mmol/l, time below 3.9mmol/l and glucose %CV measured by continuous glucose monitoring (CGM)	0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72 and 96 weeks
Estimated C-peptide concentration	Average C-peptide concentration estimated from fasting glucose, C-peptide, HbA1c, body mass index, disease duration and insulin dose	-2, 24, 48, 72 and 96 weeks
Frequency of hypoglycemic events	Frequency of glucose readings <3.0mmol/l, determined by CGM and correcting for CGM wear time	0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72 and 96 weeks
Hemoglobin A1c levels	Change in HbA1c levels	0, 12, 24, 36, 48, 60, 72 and 96 weeks
Insulin use	Daily insulin dose at all visits	Every 4 weeks for 96 weeks
Weight, body mass index and sitting blood pressure	Change in weight, body mass index and blood pressure	0, 12, 24, 48, 60, 72 and 96 weeks
Diabetes antibody levels	Insulin, GAD, IA2 and ZnT8 autoantibody concentrations	-2, 0, 4, 12, 24, 48, 60, 72 and 96 weeks
Quality of life assessment	Assessed by questionnaire	-2, 0, 24, 48, 72 and 96 weeks
Adverse events	Frequency and severity of adverse events	All visits for 96 weeks

Collaborators and Investigators

• Sponsor: Melbourne Health
• Collaborators: National Health and Medical Research Council, Australia; Juvenile Diabetes Research Foundation
• Investigators: Principal Investigator: John Wentworth, Melbourne Health

Publications and helpful links

Helpful Links

• Link to clinical trial

Study record dates

Study Major Dates

• Study Start (Actual): February 13, 2023
• Primary Completion (Actual): September 30, 2025
• Study Completion (Actual): September 30, 2025

Study Registration Dates

• First Submitted: February 15, 2023
• First Submitted That Met QC Criteria: February 15, 2023
• First Posted (Actual): February 23, 2023

Study Record Updates

• Last Update Posted (Actual): December 24, 2025
• Last Update Submitted That Met QC Criteria: December 17, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Hypoglycemia; Glucose intolerance; Abatacept; Immune responses; Beta-cell function; Nasal insulin
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Autoimmune Diseases; Immune System Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Hyperglycemia; Nutritional and Metabolic Diseases; Hypoglycemia; Diabetes Mellitus, Type 1; Glucose Intolerance; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Immunoconjugates; Peptide Hormones; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Antibodies; Immunoglobulins; Blood Proteins; Serum Globulins; Globulins; Inorganic Chemicals; Chlorine Compounds; Insulins; Pancreatic Hormones; Sodium Compounds; Proinsulin; Chlorides; Hydrochloric Acid; Abatacept; Insulin; Sodium Chloride
• Other Study ID Numbers: 2022.079

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No