Interleukin-2 Therapy of Autoimmunity in Diabetes (ITAD)

Type1 Diabetes Clinical Trial

— ITAD  

Official title:

Interleukin-2 Therapy of Autoimmunity in Diabetes (ITAD)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03782636
• Other study ID #: 13341
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 28, 2019
• Est. completion date: September 2022

Study information

• Verified date: October 2021
• Source: University of Oxford
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 41
• Est. completion date: September 2022
• Est. primary completion date: April 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 18 Years

Eligibility

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)

Related Conditions & MeSH terms

• Autoimmune Diseases
• Diabetes Mellitus
• Type1 Diabetes

Intervention

Drug:
• Aldesleukin
PROLEUKIN® 18 x 106 IU Powder for solution for injection or infusion

Other:
• Placebo
sterile diluent used for the aldesleukin preparation and 5% glucose

Locations

Country	Name	City	State
United Kingdom	Bristol Royal Hospital for Children	Bristol
United Kingdom	Addenbrooke's Hospital	Cambridge
United Kingdom	The Great North Children's Hospital	Newcastle Upon Tyne
United Kingdom	Nottingham Children's Hospital	Nottingham
United Kingdom	Oxford Children's Hospital	Oxford	Oxfordshire

Sponsors (5)

Lead Sponsor	Collaborator
University of Oxford	Centre for Statistics in Medicine, Oxford, JDRF, Oxford Clinical Trials Research Unit (OCTRU), Wellcome

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Differences in slopes of DBS (Dried Blood Spot) C-peptide over the 6 month-treatment period between the active and placebo groups.		Weekly DBS C-peptide collected during the 6-month treatment period, and then monthly during the 6 months of follow-up
Secondary	Change in Treg, Teff and NK56bright cell frequencies and phenotypes from baseline		At baseline and then1, 2 , 3, 6 and 12 months from the beginning of treatment
Secondary	Safety will be assessed at each visit (reported reactions using CTCAE grading v5.0)	Assessment of the most commonly reported reactions to low- or high-dose aldesleukin, namely influenza-like syndrome, skin reaction, diarrhoea, nausea using CTCAE grading v5.0	At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment
Secondary	Safety will be assessed at each visit (temperature in celsius)	Vital signs - temperature in celsius	At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment
Secondary	Safety will be assessed at each visit (weight, in kilograms)	Vital signs - weight, in kilograms	At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment
Secondary	Safety will be assessed at each visit (blood pressure: systolic/diastolic)	Vital signs - blood pressure: systolic/diastolic	At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment
Secondary	Safety will be assessed at each visit (heart rate: bpm)	Vital signs - heart rate: bpm	At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment
Secondary	Safety will be assessed at each visit (AST, ALT, ALP, GGT units per liter (U/L)	Abnormal laboratory parameters liver function (AST, ALT, ALP, GGT units per liter (U/L)	At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment
Secondary	Safety will be assessed at each visit total bilirubin - milligrams per deciliter (mg/dL)	Abnormal laboratory parameters liver function total bilirubin - milligrams per deciliter (mg/dL)	At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment
Secondary	Safety will be assessed at each visit (urea and creatinine - mmol/L)	Abnormal laboratory parameters kidney function (urea and creatinine - mmol/L)	At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment
Secondary	Safety will be assessed at each visit (full blood count - 109/L)	Abnormal laboratory parameters full blood count - 109/L	At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment
Secondary	Changes in the absolute numbers of T, B and NK (Natural Killer) cells.		At baseline and then, 1, 2 , 3, 6 and 12 months from the beginning of treatment
Secondary	Change in HbA1c and daily insulin requirements during the trial period.		HbA1c - At baseline and then 3,6 and 12 months Insulin dose data -Baseline and then 1, 2, 3, 6 and 12 months