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Interleukin-2 Therapy of Autoimmunity in Diabetes (ITAD) (ITAD)

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ClinicalTrials.gov Identifier: NCT03782636
Recruitment Status : Recruiting
First Posted : December 20, 2018
Last Update Posted : September 4, 2019
Sponsor:
Collaborators:
Oxford Clinical Trials Research Unit (OCTRU)
Centre for Statistics in Medicine, Oxford
Juvenile Diabetes Research Foundation
Information provided by (Responsible Party):
University of Oxford

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.


Condition or disease Intervention/treatment Phase
Type1 Diabetes Drug: Aldesleukin Other: Placebo Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Interleukin-2 Therapy of Autoimmunity in Diabetes (ITAD)
Actual Study Start Date : January 28, 2019
Estimated Primary Completion Date : April 14, 2022
Estimated Study Completion Date : April 14, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Aldesleukin

Arm Intervention/treatment
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.
Drug: Aldesleukin

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




Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]
    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

  3. 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 ]
    Vital signs - temperature in celsius

  4. 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 ]
    Vital signs - weight, in kilograms

  5. 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 ]
    Vital signs - blood pressure: systolic/diastolic

  6. 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 ]
    Vital signs - heart rate: bpm

  7. 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 ]
    Abnormal laboratory parameters liver function (AST, ALT, ALP, GGT units per liter (U/L)

  8. 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 ]
    Abnormal laboratory parameters liver function total bilirubin - milligrams per deciliter (mg/dL)

  9. 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 ]
    Abnormal laboratory parameters kidney function (urea and creatinine - mmol/L)

  10. 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 ]
    Abnormal laboratory parameters full blood count - 109/L

  11. 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 ]
  12. 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 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   6 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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. Current use of immunosuppressive agents or steroids
  12. Current treatment with hepatotoxic, nephrotoxic, myelotoxic, or cardiotoxic products
  13. 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
  14. Immunisations - participants can be recruited after a minimum of 14 days following immunisation. Routine vaccinations should be avoided for the 6-month duration of treatment and for 30 days afterwards
  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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03782636


Contacts
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Contact: Sylwia Kopijasz 01865287664 itad@well.ox.ac.uk
Contact: Claire Scudder 01865287644 itad@well.ox.ac.uk

Locations
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United Kingdom
Bristol Royal Hospital for Children Recruiting
Bristol, United Kingdom
Contact: Victoria Carter         
Principal Investigator: Dinesh Giri         
Nottingham Children's Hospital Recruiting
Nottingham, United Kingdom
Contact: Victoria Smith         
Principal Investigator: Tabitha Randell         
Sponsors and Collaborators
University of Oxford
Oxford Clinical Trials Research Unit (OCTRU)
Centre for Statistics in Medicine, Oxford
Juvenile Diabetes Research Foundation
Investigators
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Principal Investigator: Paul Johnson, Professor University of Oxford

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Responsible Party: University of Oxford
ClinicalTrials.gov Identifier: NCT03782636     History of Changes
Other Study ID Numbers: 13341
First Posted: December 20, 2018    Key Record Dates
Last Update Posted: September 4, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Autoimmune Diseases
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Immune System Diseases
Aldesleukin
Interleukin-2
Antineoplastic Agents
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents