Interleukin-2 Therapy of Autoimmunity in Diabetes (ITAD)

University of Oxford

Status and phase: Unknown; Phase 2

Conditions: Type1 Diabetes

Treatments: Other: Placebo; Drug: Aldesleukin

Study type: Interventional

Funder types: Other

Identifiers

NCT03782636

13341

Details and patient eligibility

About

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.

Full 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.

Enrollment: 41 patients

Sex: All

Ages: 6 to 18 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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41 participants in 2 patient groups, including a placebo group

Aldesleukin

Experimental group

Description:

Ultra-low dose aldesleukin injected subcutaneously, at a dose of 0.2 x 106 IU/m2 twice-weekly , three days apart, for 6 months.

Treatment:

Drug: Aldesleukin

Placebo

Placebo Comparator group

Description:

Placebo sc, at a similar dose (expressed in ml) to the active drug

Treatment:

Other: Placebo