Clinical trial NCT05742243: Insulin and Abatacept in Recently-diagnosed Type 1 Diabetes
Official title: Abatacept Combined With Nasal Insulin to Preserve Beta-cell Function in Recently-diagnosed Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Type 1 Diabetes
Diabetes Mellitus, Type 1
Keywords: Abatacept
Nasal insulin
Beta-cell function
Glucose intolerance
Immune responses
Hypoglycemia
Lead sponsor: Melbourne Health
Sponsor class: OTHER
Collaborators: name: National Health and Medical Research Council, Australia
name: Juvenile Diabetes Research Foundation
First posted: 2023-02-23
Enrollment: 62
Sex: ALL
Minimum age (years): 6
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Beta-cell function at 48 weeks
timeFrame: 0 weeks - 48 weeks
Secondary outcomes:
measure: Beta-cell function at 24, 72 and 96 weeks
timeFrame: 0, 24, 72 and 96 weeks
measure: Glucose regulation
timeFrame: 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72 and 96 weeks
measure: Estimated C-peptide concentration
timeFrame: -2, 24, 48, 72 and 96 weeks
measure: Frequency of hypoglycemic events
timeFrame: 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60, 72 and 96 weeks
measure: Hemoglobin A1c levels
timeFrame: 0, 12, 24, 36, 48, 60, 72 and 96 weeks
measure: Insulin use
timeFrame: Every 4 weeks for 96 weeks
measure: Weight, body mass index and sitting blood pressure
timeFrame: 0, 12, 24, 48, 60, 72 and 96 weeks
measure: Diabetes antibody levels
timeFrame: -2, 0, 4, 12, 24, 48, 60, 72 and 96 weeks
measure: Quality of life assessment
timeFrame: -2, 0, 24, 48, 72 and 96 weeks
measure: Adverse events
timeFrame: All visits for 96 weeks
Other outcomes:
Locations:
city: Westmead
country: Australia
facility: The Children's Hospital at Westmead
state: New South Wales
city: South Brisbane
country: Australia
facility: Queensland Children's Hospital
state: Queensland
city: North Adelaide
country: Australia
facility: Women's and Children's Hospital
state: South Australia
city: Parkville
country: Australia
facility: The Royal Melbourne Hospital
state: Victoria
city: Parkville
country: Australia
facility: The Royal Children's Hospital
state: Victoria
city: Nedlands
country: Australia
facility: Perth Children's Hospital
state: Western Australia
Study officials:
affiliation: Melbourne Health
name: John Wentworth
role: PRINCIPAL_INVESTIGATOR
References: