- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03782636
Interleukin-2 Therapy of Autoimmunity in Diabetes (ITAD) (ITAD)
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.
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Bristol, United Kingdom
- Bristol Royal Hospital for Children
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Cambridge, United Kingdom
- Addenbrooke's Hospital
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Newcastle Upon Tyne, United Kingdom
- The Great North Children's Hospital
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Nottingham, United Kingdom
- Nottingham Children's Hospital
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Oxfordshire
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Oxford, Oxfordshire, United Kingdom, OX3 9DU
- Oxford Children's Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Have given written informed consent to participate or assent with parental consent
- Be aged 6-18 years
- Be diagnosed with T1D (Type 1 Diabetes) (at least one autoantibody positive), requiring insulin treatment
- Be within 6 weeks from diagnosis of T1D (at screening)
- Have a random C-peptide > 200 pmol/l
- Normal full blood count
Exclusion Criteria:
- Non-type 1 diabetes (type 2 or monogenic diabetes) and secondary diabetes
- Pre-existing autoimmune disease (excluding type 1 diabetes)
- Hypersensitivity to aldesleukin or any of the excipients
- History of severe cardiac disease (NYHA Class III or IV)
- History of malignancy within the past 5 years (with the exception of adequately treated basal or squamous cell carcinoma or cervical carcinoma in situ)
- Clinically significant abnormal laboratory values (out of range and associated with clinical symptoms or signs) in haematology, biochemistry, thyroid, liver and kidney function
- Pre-existing severe major organ dysfunction or seizure disorders
- Participation in another clinical trial (CTIMP) within 4 months prior to screening
- Females who are pregnant, lactating or intend to get pregnant during the study
- Females of childbearing potential who are unwilling or unable to comply with contraceptive advice and regular pregnancy testing throughout the trial
- Sexually active males who are unwilling or unable to comply with contraceptive advice
- Current use of immunosuppressive agents or steroids
- Current treatment with hepatotoxic, nephrotoxic, myelotoxic, or cardiotoxic products
- 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
- 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
- Children with compliance problems (families where the local investigators consider that problems with compliance may be an issue)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: TRIPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: Aldesleukin
Ultra-low dose aldesleukin injected subcutaneously, at a dose of 0.2 x 106 IU/m2 twice-weekly , three days apart, for 6 months.
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PROLEUKIN® 18 x 106 IU Powder for solution for injection or infusion |
PLACEBO_COMPARATOR: Placebo
Placebo sc, at a similar dose (expressed in ml) to the active drug
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sterile diluent used for the aldesleukin preparation and 5% glucose
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Differences in slopes of DBS (Dried Blood Spot) C-peptide over the 6 month-treatment period between the active and placebo groups.
Time Frame: Weekly DBS C-peptide collected during the 6-month treatment period, and then monthly during the 6 months of follow-up
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Weekly DBS C-peptide collected during the 6-month treatment period, and then monthly during the 6 months of follow-up
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Treg, Teff and NK56bright cell frequencies and phenotypes from baseline
Time Frame: At baseline and then1, 2 , 3, 6 and 12 months from the beginning of treatment
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At baseline and then1, 2 , 3, 6 and 12 months from the beginning of treatment
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Safety will be assessed at each visit (reported reactions using CTCAE grading v5.0)
Time Frame: At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment
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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
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At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment
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Safety will be assessed at each visit (temperature in celsius)
Time Frame: At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment
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Vital signs - temperature in celsius
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At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment
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Safety will be assessed at each visit (weight, in kilograms)
Time Frame: At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment
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Vital signs - weight, in kilograms
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At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment
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Safety will be assessed at each visit (blood pressure: systolic/diastolic)
Time Frame: At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment
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Vital signs - blood pressure: systolic/diastolic
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At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment
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Safety will be assessed at each visit (heart rate: bpm)
Time Frame: At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment
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Vital signs - heart rate: bpm
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At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment
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Safety will be assessed at each visit (AST, ALT, ALP, GGT units per liter (U/L)
Time Frame: At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment
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Abnormal laboratory parameters liver function (AST, ALT, ALP, GGT units per liter (U/L)
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At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment
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Safety will be assessed at each visit total bilirubin - milligrams per deciliter (mg/dL)
Time Frame: At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment
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Abnormal laboratory parameters liver function total bilirubin - milligrams per deciliter (mg/dL)
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At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment
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Safety will be assessed at each visit (urea and creatinine - mmol/L)
Time Frame: At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment
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Abnormal laboratory parameters kidney function (urea and creatinine - mmol/L)
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At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment
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Safety will be assessed at each visit (full blood count - 109/L)
Time Frame: At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment
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Abnormal laboratory parameters full blood count - 109/L
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At screening, baseline and then 1, 2 , 3, 6 and 12 months from the beginning of treatment
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Changes in the absolute numbers of T, B and NK (Natural Killer) cells.
Time Frame: At baseline and then, 1, 2 , 3, 6 and 12 months from the beginning of treatment
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At baseline and then, 1, 2 , 3, 6 and 12 months from the beginning of treatment
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Change in HbA1c and daily insulin requirements during the trial period.
Time Frame: HbA1c - At baseline and then 3,6 and 12 months Insulin dose data -Baseline and then 1, 2, 3, 6 and 12 months
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HbA1c - At baseline and then 3,6 and 12 months Insulin dose data -Baseline and then 1, 2, 3, 6 and 12 months
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Paul Johnson, Professor, University of Oxford
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 13341
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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