Type 1 DiabetesPhase 2DFIL2-ChildNCT01862120
Dose Finding Study of Il-2 at Ultra-low Dose in Children With Recently Diagnosed Type 1 Diabetes
A Phase 2 study testing Dose D1 of interleukin-2, Dose D2 of Interleukin-2 and Dose D3 of interleukin-2 in people with Type 1 Diabetes, run by Assistance Publique - Hôpitaux de Paris at 6 sites in France.
Trial summary
Human recombinant interleukin-2 (rhIL-2) is a biological signalling protein playing a key role in the regulation of the immune system. At high doses, rhIL-2 activates the immune effectors T cells (TEFFS) while at low doses rhIL-2 induces and activates regulatory T cells (TREGS), a population of immune cells… Read more about this study
- Who is it for?
- Ages 7 to 14 years
- Conditions the study is for
- Type 1 Diabetes
- What is being tested?
- Dose D1 of interleukin-2, Dose D2 of Interleukin-2 and Dose D3 of interleukin-2
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 6 sitesFrance
- Study dates
- 27 Jun 2013to 16 Mar 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 7 to 14 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Age [7-13] years for girls and [7-14] years for boys
- With a T1D diagnosis (as ADA)
- Treated with insulin for ≤ 3 months,
- With at least one auto-antibody among: anti-insulin, anti-GAD, anti-IA2, anti-ZnT8 ;
- No clinically relevant abnormal findings for haematology, biochemistry, liver and kidney functions
- Informed consent signed by the patient, the parents, and the investigator before any intervention necessary for the trial.
Who cannot join
- Contra-indications to IL-2 :
- Hyper sensibility to IL-2 or its excipients,
- Severe cardiopathy
- Previous organ allograft
- Ongoing infection requiring antibiotherapy,
- O2 Saturation ≤ 90 %
Show all 20Show fewer
- Severe impairment of any vital organ
- Documented history of other auto-immune diseases (except for auto-antibodies for, IAA, GADA, IA-2A, anti-ZnT8A, and stable thyroiditis with normal TSH (<10 mUI/L), T3 and, T4 levels.
- Diabetes onset characteristics including:
- Continuous nocturnal polyuria ≥ 3 months ;
- Inaugural acidosis (with venous Ph < 7.25) ;
- HbA1c at diagnostic ≥ 13%;
- Weight loss ≥ 10 % at diagnosis ;
- Positive autoantibodies to 21-hydroxylase
- Stage 2 obesity
- Non authorized concomitant treatment : immuno-modulators, cytotoxic drugs, drug modifying plasma glycemia
- vaccination ≤ 4 weeks with life vaccin
- Positive serology (IgM) to the Epstein-Barr virus (EBV) and/or cytomegalovirus (CMV), reflecting an acute infection.
- Participation to another clinical investigation in previous 3 months
- No affiliation to National Health Insurance
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
France6 sites
Service d'Endocrinologie Pédiatrique
Le Kremlin-Bicêtre, 94275
Service de Pédiatrie - CHU de Nîmes
Nîmes, 30029 cedex 9
CIC pédiatrique - CHU de Necker
Paris, 75015
Service d'endocrinologie pédiatrique - CHU de Necker
Paris, 75015
CIC 9202 CHU Rober Débré
Paris, 75019
Service d'endocrinologie Diabétologie pédiatrique CHU Robert Débré
Paris, 75019
About this study
Official title: Induction of Regulatory T Cells for the Treatment of Recently Diagnosed Type 1 Diabetes: Dose Finding Study of the Lowest Active Dose of IL-2 in Children
Human recombinant interleukin-2 (rhIL-2) is a biological signalling protein playing a key role in the regulation of the immune system. At high doses, rhIL-2 activates the immune effectors T cells (TEFFS) while at low doses rhIL-2 induces and activates regulatory T cells (TREGS), a population of immune cells controlling the immune Teff response. In patients with Type 1 Diabetes (T1D), TREGS fail to control the autoimmune destruction by TEFFS of pancreatic beta-cells producing insulin. The investigator recently showed that rhIL-2 at low dose is well tolerated in patients with an autoimmune disease and in adults with established T1D, inducing TREGS without effects on TEFFS. The investigators aim to use rhIL-2 at low dose to induce/stimulate TREGS in young recently diagnosed T1D patients. This study will investigate the dose effect relationship of low dose rhIL-2 on TREG induction such as to optimize the risk benefit ratio of this treatment in T1D. Through Treg induction, the investigators aim to protect the remaining/regenerating pancreatic β-cells from autoimmune destruction, thus improving or even curing T1D.
Read the detailed description
Main objective:
Define the lowest dose of rhIL-2 inducing TREGS in children with recently diagnosed type 1 diabetes.
Conduct of the study:
Three doses will be studied versus placebo in parallel groups of six patients. Each dose or placebo will be studied according to three periods of treatment:
- Induction of TREGS following a cure of 5 days repeated once daily administration [day 1 - day 5].
- Maintenance of TREGS following repeated administration once every two weeks for one year [day 15 - day 337].
At each treatment period, Treg response and tolerance will be evaluated. In addition, overall response on T1D parameters will be assessed throughout the study.
- Conditions
- Type 1 Diabetes
- Being tested
- Dose D1 of interleukin-2, placebo, Dose D2 of Interleukin-2, Dose D3 of interleukin-2
- Keywords
- Recently diagnosed, Regulatory T Cells, Tolerance Induction, Paediatrics, Low dose, IL-2
- Medical subject headings
- Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dose D1 of interleukin-2Drug
subcutaneous injection of Interleukin-2 during 5 days, once daily repeated administration(Induction period). At day 15 single administration of Interleukin-2 every two weeks during one year (maintenance period).
placeboDrug
subcutaneous injection of Interleukin-2 during 5 days, once daily repeated administration(Induction period). At day 15 single administration of Interleukin-2 every two weeks during one year (maintenance period).
Dose D2 of Interleukin-2Drug
subcutaneous injection of Interleukin-2 during 5 days, once daily repeated administration(Induction period). At day 15 single administration of Interleukin-2 every two weeks during one year (maintenance period).
Dose D3 of interleukin-2Drug
subcutaneous injection of Interleukin-2 during 5 days, once daily repeated administration(Induction period). At day 15 single administration of Interleukin-2 every two weeks during one year (maintenance period).
| Study group | Role | What they receive |
|---|---|---|
| interleukin-2 | Experimental | Dose D1 of interleukin-2 Receives: Drug: Dose D1 of interleukin-2 |
| Dose D2 of interleukin-2 | Experimental | Dose D2 of interleukin-2 Receives: Drug: Dose D2 of Interleukin-2 |
| Dose D3 of interleukin-2 | Experimental | Dose D3 of interleukin-2 Receives: Drug: Dose D3 of interleukin-2 |
| placebo | Placebo comparator | placebo Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treg response following the induction cure period
expressed as % total CD4 cells
Measured: day 5
Secondary outcomes (6)
Fasting plasma concentration of C-peptide
Measured: at Day 0, 99, 183, 267, 351, 436
C-peptide AUC response to a mixed meal tolerance test
Measured: at baseline, at months 6, 12, 15
IDAA1C score
is a score defined as A1C (percent) + [4 x insulin dose (units per kilogram per 24 h)] without unit
Measured: at baseline, at months 3, 6, 9, 12, 15
HbA1c
Measured: at baseline, at months 3, 6, 9, 12, 15
Treg response after the last administration
Measured: day 351, day 436
Treg response during the maintenance period compare to the baseline
Treg response expressed as the % / CD4 will be measured several times
Measured: day 15, day 29, day 43, day 99, day 183, day 267
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2013 (estimated)
- Study start27 Jun 2013
- Primary completion8 Jul 2016
- Study completion16 Mar 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type 1 DiabetesStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- David Klatzmann, MD, PhD, Principal investigator, APHP
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01862120
- Sponsor's protocol ID
- P101106
- Acronym
- DFIL2-Child
- Status last verified
- Nov 2020
- First submitted
- 10 Dec 2012
- Last updated
- 12 Nov 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Rosenzwajg M, Salet R, Lorenzon R, Tchitchek N, Roux A, Bernard C, Carel JC, Storey C, Polak M, Beltrand J, Amouyal C, Hartemann A, Corbeau P, Vicaut E, Bibal C, Bougneres P, Tran TA, Klatzmann D. Low-dose IL-2 in children with recently diagnosed type 1 diabetes: a Phase I/II randomised, double-blind, placebo-controlled, dose-finding study. Diabetologia. 2020 Sep;63(9):1808-1821. doi: 10.1007/s00125-020-05200-w. Epub 2020 Jul 1.
PubMed 32607749
Study at a glance
From the registry record, last updated by the sponsor on 12 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Induction of Regulatory T Cells for the Treatment of Recently Diagnosed Type 1 Diabetes: Dose Finding Study of the Lowest Active Dose of IL-2 in Children
- ClinicalTrials.gov ID
- NCT01862120
- Acronym / sponsor ID
- DFIL2-Child / P101106
- Conditions
- Type 1 Diabetes
- Keywords
- Recently diagnosed, Regulatory T Cells, Tolerance Induction, Paediatrics, Low dose, IL-2
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 27 Jun 2013 (actual)
- Primary completion
- 8 Jul 2016 (actual)
- Study completion
- 16 Mar 2017 (actual)
- First posted
- 24 May 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Human recombinant interleukin-2 (rhIL-2) is a biological signalling protein playing a key role in the regulation of the immune system. At high doses, rhIL-2 activates the immune effectors T cells (TEFFS) while at low doses rhIL-2 induces and activates regulatory T cells (TREGS), a population of immune cells controlling the immune Teff response. In patients with Type 1 Diabetes (T1D), TREGS fail to control the autoimmune destruction by TEFFS of pancreatic beta-cells producing insulin. The investigator recently showed that rhIL-2 at low dose is well tolerated in patients with an autoimmune disease and in adults with established T1D, inducing TREGS without effects on TEFFS. The investigators aim to use rhIL-2 at low dose to induce/stimulate TREGS in young recently diagnosed T1D patients. This study will investigate the dose effect relationship of low dose rhIL-2 on TREG induction such as to optimize the risk benefit ratio of this treatment in T1D. Through Treg induction, the investigators aim to protect the remaining/regenerating pancreatic β-cells from autoimmune destruction, thus improving or even curing T1D.
Detailed description
Main objective:
Define the lowest dose of rhIL-2 inducing TREGS in children with recently diagnosed type 1 diabetes.
Conduct of the study:
Three doses will be studied versus placebo in parallel groups of six patients. Each dose or placebo will be studied according to three periods of treatment:
- Induction of TREGS following a cure of 5 days repeated once daily administration [day 1 - day 5].
- Maintenance of TREGS following repeated administration once every two weeks for one year [day 15 - day 337].
At each treatment period, Treg response and tolerance will be evaluated. In addition, overall response on T1D parameters will be assessed throughout the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| interleukin-2 | Experimental | Drug: Dose D1 of interleukin-2Dose D1 of interleukin-2 |
| Dose D2 of interleukin-2 | Experimental | Drug: Dose D2 of Interleukin-2Dose D2 of interleukin-2 |
| Dose D3 of interleukin-2 | Experimental | Drug: Dose D3 of interleukin-2Dose D3 of interleukin-2 |
| placebo | Placebo comparator | Drug: placeboplacebo |
Who may qualify
- Ages
- 7 to 14 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Age [7-13] years for girls and [7-14] years for boys
- No clinically relevant abnormal findings for haematology, biochemistry, liver and kidney functions
- Informed consent signed by the patient, the parents, and the investigator before any intervention necessary for the trial.
Key exclusion criteria (20 listed)
- Contra-indications to IL-2 :
- Non authorized concomitant treatment : immuno-modulators, cytotoxic drugs, drug modifying plasma glycemia
- vaccination ≤ 4 weeks with life vaccin
- Positive serology (IgM) to the Epstein-Barr virus (EBV) and/or cytomegalovirus (CMV), reflecting an acute infection.
- Participation to another clinical investigation in previous 3 months
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dose D1 of interleukin-2subcutaneous injection of Interleukin-2 during 5 days, once daily repeated administration(Induction period). At day 15 single administration of Interleukin-2 every two weeks during one year (maintenance period). | Drug | interleukin-2 |
| placebosubcutaneous injection of Interleukin-2 during 5 days, once daily repeated administration(Induction period). At day 15 single administration of Interleukin-2 every two weeks during one year (maintenance period). | Drug | placebo |
| Dose D2 of Interleukin-2subcutaneous injection of Interleukin-2 during 5 days, once daily repeated administration(Induction period). At day 15 single administration of Interleukin-2 every two weeks during one year (maintenance period). | Drug | Dose D2 of interleukin-2 |
| Dose D3 of interleukin-2subcutaneous injection of Interleukin-2 during 5 days, once daily repeated administration(Induction period). At day 15 single administration of Interleukin-2 every two weeks during one year (maintenance period). | Drug | Dose D3 of interleukin-2 |
Primary outcome
Treg response following the induction cure period
Time frame: day 5
expressed as % total CD4 cells
6 secondary outcomes
Fasting plasma concentration of C-peptide
Time frame: at Day 0, 99, 183, 267, 351, 436
C-peptide AUC response to a mixed meal tolerance test
Time frame: at baseline, at months 6, 12, 15
IDAA1C score
Time frame: at baseline, at months 3, 6, 9, 12, 15
HbA1c
Time frame: at baseline, at months 3, 6, 9, 12, 15
Treg response after the last administration
Time frame: day 351, day 436
Treg response during the maintenance period compare to the baseline
Time frame: day 15, day 29, day 43, day 99, day 183, day 267
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Nov 2020.
- Derived from this study: PubMed 32607749Rosenzwajg M, Salet R, Lorenzon R, Tchitchek N, Roux A, Bernard C, Carel JC, Storey C, Polak M, Beltrand J, Amouyal C, Hartemann A, Corbeau P, Vicaut E, Bibal C, Bougneres P, Tran TA, Klatzmann D. Low-dose IL-2 in children with recently diagnosed type 1 diabetes: a Phase I/II randomised, double-blind, placebo-controlled, dose-finding study. Diabetologia. 2020 Sep;63(9):1808-1821. doi: 10.1007/s00125-020-05200-w. Epub 2020 Jul 1.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Klatzmann, MD, PhD principal investigator
APHP
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Dose D1 of interleukin-2, Dose D2 of Interleukin-2 and Dose D3 of interleukin-2 in people with Type 1 Diabetes, run by Assistance Publique - Hôpitaux de Paris at 6 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treg response following the induction cure period (time frame: day 5). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01862120, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Nov 2020.