Insulin and Abatacept in Recently-diagnosed Type 1 Diabetes

Type 1 Diabetes Clinical Trial

— IAA  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05742243
• Other study ID #: 2022.079
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: February 13, 2023
• Est. completion date: February 13, 2027

Study information

• Verified date: April 2024
• Source: Melbourne Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 62
• Est. completion date: February 13, 2027
• Est. primary completion date: February 13, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 21 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes

Intervention

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
• 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

Locations

Country	Name	City	State
Australia	Perth Children's Hospital	Nedlands	Western Australia
Australia	Women's and Children's Hospital	North Adelaide	South Australia
Australia	The Royal Children's Hospital	Parkville	Victoria
Australia	The Royal Melbourne Hospital	Parkville	Victoria
Australia	Queensland Children's Hospital	South Brisbane	Queensland
Australia	The Children's Hospital at Westmead	Westmead	New South Wales

Sponsors (3)

Lead Sponsor	Collaborator
Melbourne Health	Juvenile Diabetes Research Foundation, National Health and Medical Research Council, Australia

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Beta-cell function at 48 weeks	Change in average C-peptide concentration during a 2-hour mixed meal challenge	0 weeks - 48 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Hemoglobin A1c levels	Change in HbA1c levels	0, 12, 24, 36, 48, 60, 72 and 96 weeks
Secondary	Insulin use	Daily insulin dose at all visits	Every 4 weeks for 96 weeks
Secondary	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
Secondary	Diabetes antibody levels	Insulin, GAD, IA2 and ZnT8 autoantibody concentrations	-2, 0, 4, 12, 24, 48, 60, 72 and 96 weeks
Secondary	Quality of life assessment	Assessed by questionnaire	-2, 0, 24, 48, 72 and 96 weeks
Secondary	Adverse events	Frequency and severity of adverse events	All visits for 96 weeks

External Links

•   Link to clinical trial