Clinical trial NCT03782636: Interleukin-2 Therapy of Autoimmunity in Diabetes (ITAD)
Official title: Interleukin-2 Therapy of Autoimmunity in Diabetes (ITAD)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Type1 Diabetes
Lead sponsor: University of Oxford
Sponsor class: OTHER
Collaborators: name: Oxford Clinical Trials Research Unit (OCTRU)
name: Centre for Statistics in Medicine, Oxford
name: Juvenile Diabetes Research Foundation
name: Wellcome Trust
First posted: 2018-12-20
Enrollment: 41
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main purpose of this study is to see if a drug called aldesleukin, can preserve insulin production in children and young adults recently diagnosed with type 1 diabetes.

One group will receive aldesleukin and the other a placebo.

Detailed description: Investigators know that the longer people with diabetes can produce their own insulin, the better it is for the control of their blood glucose levels and long-term complications.

People get type 1 diabetes because their immune system, the part of the body, which helps fight infections, mistakenly attacks and destroys the beta cells in the pancreas that produce insulin. As the immune system destroys these insulin-producing cells, the body's own ability to produce insulin decreases and diabetes develops.

At diagnosis, there are usually a small number of beta cells (10-20%) left in the pancreas, which still produce small amounts of insulin. This is called 'beta cell function' and it is assessed by measuring C-peptide, which is a protein made by the pancreas when insulin is produced. Most people with type 1 diabetes eventually stop producing insulin themselves, this may occur rapidly in a few months, or more slowly over several years.

New treatments preserving insulin production could improve management of diabetes. This could be done by using drugs acting on cells of the immune system. In type 1 diabetes, there is an imbalance between cells of the immune system, and there is evidence that one protein produced by our body, called Interleukin-2, could help in resetting the balance between those cells. It is important to start this treatment soon after diagnosis because this when there is the best chance of saving the beta cells still left in the pancreas.

Eligibility criteria: Inclusion Criteria:

1. Have given written informed consent to participate or assent with parental consent
2. Be aged 6-18 years
3. Be diagnosed with T1D (Type 1 Diabetes) (at least one autoantibody positive), requiring insulin treatment
4. Be within 6 weeks from diagnosis of T1D (at screening)
5. Have a random C-peptide \> 200 pmol/l
6. Normal full blood count

Exclusion Criteria:

1. Non-type 1 diabetes (type 2 or monogenic diabetes) and secondary diabetes
2. Pre-existing autoimmune disease (excluding type 1 diabetes)
3. Hypersensitivity to aldesleukin or any of the excipients
4. History of severe cardiac disease (NYHA Class III or IV)
5. History of malignancy within the past 5 years (with the exception of adequately treated basal or squamous cell carcinoma or cervical carcinoma in situ)
6. Clinically significant abnormal laboratory values (out of range and associated with clinical symptoms or signs) in haematology, biochemistry, thyroid, liver and kidney function
7. Pre-existing severe major organ dysfunction or seizure disorders
8. Participation in another clinical trial (CTIMP) within 4 months prior to screening
9. Females who are pregnant, lactating or intend to get pregnant during the study
10. Females of childbearing potential who are unwilling or unable to comply with contraceptive advice and regular pregnancy testing throughout the trial
11. Sexually active males who are unwilling or unable to comply with contraceptive advice
12. Current use of immunosuppressive agents or steroids
13. Current treatment with hepatotoxic, nephrotoxic, myelotoxic, or cardiotoxic products
14. Active clinical infections - participants can be recruited after a minimum period of 48 h after last day of feeling unwell or last day of antibiotic/anti-viral treatment
15. Any medical history or clinically relevant abnormality that is deemed by the principal investigator and/or medical monitor to make the participant ineligible for inclusion because of a safety concern
16. Children with compliance problems (families where the local investigators consider that problems with compliance may be an issue)

Primary outcomes:
measure: Differences in slopes of DBS (Dried Blood Spot) C-peptide over the 6 month-treatment period between the active and placebo groups.
timeFrame: Weekly DBS C-peptide collected during the 6-month treatment period, and then monthly during the 6 months of follow-up
Secondary outcomes:
measure: Change in Treg, Teff and NK56bright cell frequencies and phenotypes from baseline
timeFrame: At baseline and then1, 2 , 3, 6 and 12 months from the beginning of treatment
measure: Safety will be assessed at each visit (reported reactions using CTCAE grading v5.0)
timeFrame: At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment
measure: Safety will be assessed at each visit (temperature in celsius)
timeFrame: At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment
measure: Safety will be assessed at each visit (weight, in kilograms)
timeFrame: At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment
measure: Safety will be assessed at each visit (blood pressure: systolic/diastolic)
timeFrame: At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment
measure: Safety will be assessed at each visit (heart rate: bpm)
timeFrame: At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment
measure: Safety will be assessed at each visit (AST, ALT, ALP, GGT units per liter (U/L)
timeFrame: At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment
measure: Safety will be assessed at each visit total bilirubin - milligrams per deciliter (mg/dL)
timeFrame: At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment
measure: Safety will be assessed at each visit (urea and creatinine - mmol/L)
timeFrame: At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment
measure: Safety will be assessed at each visit (full blood count - 109/L)
timeFrame: At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment
measure: Changes in the absolute numbers of T, B and NK (Natural Killer) cells.
timeFrame: At baseline and then, 1, 2 , 3, 6 and 12 months from the beginning of treatment
measure: Change in HbA1c and daily insulin requirements during the trial period.
timeFrame: HbA1c - At baseline and then 3,6 and 12 months Insulin dose data -Baseline and then 1, 2, 3, 6 and 12 months
Other outcomes:
Locations:
city: Oxford
country: United Kingdom
facility: Oxford Children's Hospital
state: Oxfordshire
city: Bristol
country: United Kingdom
facility: Bristol Royal Hospital for Children
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: Newcastle Upon Tyne
country: United Kingdom
facility: The Great North Children's Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham Children's Hospital
Study officials:
affiliation: University of Oxford
name: Paul Johnson, Professor
role: PRINCIPAL_INVESTIGATOR
References: