EncephalitisPhase 1/2NCT02714959
IL-2 in Refractory Autoimmune Encephalitis
A Phase 1/2 study testing Proleukin in people with Encephalitis, run by Seoul National University Hospital.
Trial summary
The purpose of this study is to determine whether low-dose IL-2 is effective in refractory autoimmune encephalitis. Read more about this study
- Who is it for?
- Ages 19 to 80 years
- Conditions the study is for
- Encephalitis
- What is being tested?
- Proleukin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- No sites listed yet
- Study dates
- Mar 2016to 12 Jun 2019
- Phase
- Phase 1/2
- 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 19 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age > 18 years
- Clinical diagnosis of autoimmune encephalitis
- Positive for autoantibody (serum and or CSF) : NMDAR, anti-leucine-rich glioma inactivated-1(LGI-1), contactin-associated protein-like 2 (CASPR2), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA) 1, AMPA2, GABAB-R, anti-Hu, -Yo, -Ri, -Ma2, -CV2/collapsing response mediator protein 5 (CRMP5), -amphiphysin, or glutamic acid decarboxylase (GAD)
- Refractory to first-line (high-dose steroid or intravenous immunoglobulin) and second line (rituximab or cyclophosphamide) immunotherapy
- Written informed consent form.
Who cannot join
- low hemoglobin <8.0 g/dL, absolute neutrophil count<1600/mm3, lymphocytes <600/mm3, platelets <140,000/mm3
- heart failure (≥ grade III NYHA), hepatic insufficiency (aspartate amino transferase >200 IU/L, amino alanine transferase, >200 IU/L), or lung failure
- Positive for HIV serology, active hepatitis B
- Significant abnormality in chest X-ray other than these linked to the diseases under investigation
- Infection
- Other progressive neurological degenerative disease.
- Poor venous access not allowing repeated blood tests
- pregnant or lactating women
About this study
Official title: Effect of IL-2 in Refractory Autoimmune Encephalitis Patients: A Pilot Study
The purpose of this study is to determine whether low-dose IL-2 is effective in refractory autoimmune encephalitis.
Read the detailed description
Autoimmune encephalitis is a recently recognized etiology of encephalitis which is mediated by various autoantibodies targeting neural cells or synapses. The responses to immunotherapy is generally good, considerable proportion of patients with autoimmune encephalitis have unfavorable clinical outcomes. Recently, depletion of regulatory T cell (Treg cell) is reported in variable autoimmune diseases and multiple studies have shown that low-dose interleukin-2(IL-2) specifically activates Treg cells to control autoimmunity and inflammation.
Protocol: This study is a single arm open-label study assessing clinical responses to the administration of low-dose IL-2 in autoimmune encephalitis patients who are refractory to first- and second-line immunotherapy.
Objective: To assess the efficacy of low-dose IL-2 in autoimmune encephalitis, resistant to first- and second- line immunotherapy.
Methods: This is a single arm open-label study. Each patients will receive four cycles of subcutaneous Proleukin (Interleukin-2, IL-2) (Week-1; 1.5 million IU (MIU)/d from Day-1 to Day-5, Week-3, -6, -9; 3MIU/d from Day-1 to Day-5) in the hospital. The patients will be followed up for 3 months (Week-21).
Primary outcome - clinical efficacy by modified Rankin Scale Secondary outcome - Immunologic follow-up of Treg cells before, during, and after IL-2 therapy, quality of life, cognitive function, side effect of low-dose IL-2
- Conditions
- Encephalitis
- Being tested
- Proleukin
- Medical subject headings
- Encephalitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ProleukinDrug
| Study group | Role | What they receive |
|---|---|---|
| Proleukin | Experimental | Proleukin (subcutaneous injection) 1.5 MIU/day from day 1 to 5 at W1 3 MIU/day from day 1 to day 5 at W3, W6, and W9 Receives: Drug: Proleukin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change of modified Rankin scale
Measured: Week 0,12
Secondary outcomes (5)
The change of percentage of regulatory T (Treg) cells
Measured: Week 1, 3, 5, 9, 12, 21
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Measured: Week 1, 3, 5, 9, 12, 21
Quality of Life in Epilepsy Inventory (QOLIE)-31
Quality of Life in Epilepsy Inventory (QOLIE)-31
Measured: Week 21
Beck Depression Inventory (BDI)
Beck Depression Inventory (BDI)
Measured: Week 21
Cognitive function
Mini-mental state examination (MMSE)
Measured: Week 21
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2016 (estimated)
- Study startMar 2016
- Primary completion12 Jun 2019
- Study completion12 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for EncephalitisStudies of the same condition, open and under way.
- More trials run by Seoul National University HospitalThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Seoul National University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kon Chu, Seoul National University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02714959
- Sponsor's protocol ID
- 1510112713
- Status last verified
- Sep 2021
- First submitted
- 14 Mar 2016
- Last updated
- 29 Sep 2021
- Results posted
- No
Publications
Klatzmann D, Abbas AK. The promise of low-dose interleukin-2 therapy for autoimmune and inflammatory diseases. Nat Rev Immunol. 2015 May;15(5):283-94. doi: 10.1038/nri3823. Epub 2015 Apr 17.
PubMed 25882245Saadoun D, Rosenzwajg M, Joly F, Six A, Carrat F, Thibault V, Sene D, Cacoub P, Klatzmann D. Regulatory T-cell responses to low-dose interleukin-2 in HCV-induced vasculitis. N Engl J Med. 2011 Dec 1;365(22):2067-77. doi: 10.1056/NEJMoa1105143.
PubMed 22129253Hartemann A, Bensimon G, Payan CA, Jacqueminet S, Bourron O, Nicolas N, Fonfrede M, Rosenzwajg M, Bernard C, Klatzmann D. Low-dose interleukin 2 in patients with type 1 diabetes: a phase 1/2 randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2013 Dec;1(4):295-305. doi: 10.1016/S2213-8587(13)70113-X. Epub 2013 Oct 8.
PubMed 24622415Rosenzwajg M, Churlaud G, Mallone R, Six A, Derian N, Chaara W, Lorenzon R, Long SA, Buckner JH, Afonso G, Pham HP, Hartemann A, Yu A, Pugliese A, Malek TR, Klatzmann D. Low-dose interleukin-2 fosters a dose-dependent regulatory T cell tuned milieu in T1D patients. J Autoimmun. 2015 Apr;58:48-58. doi: 10.1016/j.jaut.2015.01.001. Epub 2015 Jan 26.
PubMed 25634360Castela E, Le Duff F, Butori C, Ticchioni M, Hofman P, Bahadoran P, Lacour JP, Passeron T. Effects of low-dose recombinant interleukin 2 to promote T-regulatory cells in alopecia areata. JAMA Dermatol. 2014 Jul;150(7):748-51. doi: 10.1001/jamadermatol.2014.504.
PubMed 24872229Humrich JY, von Spee-Mayer C, Siegert E, Alexander T, Hiepe F, Radbruch A, Burmester GR, Riemekasten G. Rapid induction of clinical remission by low-dose interleukin-2 in a patient with refractory SLE. Ann Rheum Dis. 2015 Apr;74(4):791-2. doi: 10.1136/annrheumdis-2014-206506. Epub 2015 Jan 21. No abstract available.
PubMed 25609413
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of IL-2 in Refractory Autoimmune Encephalitis Patients: A Pilot Study
- ClinicalTrials.gov ID
- NCT02714959
- Acronym / sponsor ID
- 1510112713
- Conditions
- Encephalitis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Seoul National University HospitalUniversity, hospital or other
- Study start
- Mar 2016
- Primary completion
- 12 Jun 2019 (actual)
- Study completion
- 12 Jun 2019 (actual)
- First posted
- 22 Mar 2016 (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.
The purpose of this study is to determine whether low-dose IL-2 is effective in refractory autoimmune encephalitis.
Detailed description
Autoimmune encephalitis is a recently recognized etiology of encephalitis which is mediated by various autoantibodies targeting neural cells or synapses. The responses to immunotherapy is generally good, considerable proportion of patients with autoimmune encephalitis have unfavorable clinical outcomes. Recently, depletion of regulatory T cell (Treg cell) is reported in variable autoimmune diseases and multiple studies have shown that low-dose interleukin-2(IL-2) specifically activates Treg cells to control autoimmunity and inflammation.
Protocol: This study is a single arm open-label study assessing clinical responses to the administration of low-dose IL-2 in autoimmune encephalitis patients who are refractory to first- and second-line immunotherapy.
Objective: To assess the efficacy of low-dose IL-2 in autoimmune encephalitis, resistant to first- and second- line immunotherapy.
Methods: This is a single arm open-label study. Each patients will receive four cycles of subcutaneous Proleukin (Interleukin-2, IL-2) (Week-1; 1.5 million IU (MIU)/d from Day-1 to Day-5, Week-3, -6, -9; 3MIU/d from Day-1 to Day-5) in the hospital. The patients will be followed up for 3 months (Week-21).
Primary outcome - clinical efficacy by modified Rankin Scale Secondary outcome - Immunologic follow-up of Treg cells before, during, and after IL-2 therapy, quality of life, cognitive function, side effect of low-dose IL-2
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Proleukin | Experimental | Drug: ProleukinProleukin (subcutaneous injection) 1.5 MIU/day from day 1 to 5 at W1 3 MIU/day from day 1 to day 5 at W3, W6, and W9 |
Who may qualify
- Ages
- 19 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age > 18 years
- Clinical diagnosis of autoimmune encephalitis
- Positive for autoantibody (serum and or CSF) : NMDAR, anti-leucine-rich glioma inactivated-1(LGI-1), contactin-associated protein-like 2 (CASPR2), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA) 1, AMPA2, GABAB-R, anti-Hu, -Yo, -Ri, -Ma2, -CV2/collapsing response mediator protein 5 (CRMP5), -amphiphysin, or glutamic acid decarboxylase (GAD)
- Refractory to first-line (high-dose steroid or intravenous immunoglobulin) and second line (rituximab or cyclophosphamide) immunotherapy
- Written informed consent form.
Key exclusion criteria (8 listed)
- low hemoglobin <8.0 g/dL, absolute neutrophil count<1600/mm3, lymphocytes <600/mm3, platelets <140,000/mm3
- heart failure (≥ grade III NYHA), hepatic insufficiency (aspartate amino transferase >200 IU/L, amino alanine transferase, >200 IU/L), or lung failure
- Positive for HIV serology, active hepatitis B
- Significant abnormality in chest X-ray other than these linked to the diseases under investigation
- Infection
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 |
|---|---|---|
| Proleukin | Drug | Proleukin |
Primary outcome
Change of modified Rankin scale
Time frame: Week 0,12
5 secondary outcomes
The change of percentage of regulatory T (Treg) cells
Time frame: Week 1, 3, 5, 9, 12, 21
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: Week 1, 3, 5, 9, 12, 21
Quality of Life in Epilepsy Inventory (QOLIE)-31
Time frame: Week 21
Beck Depression Inventory (BDI)
Time frame: Week 21
Cognitive function
Time frame: Week 21
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 29 Sep 2021.
- Background: PubMed 25882245Klatzmann D, Abbas AK. The promise of low-dose interleukin-2 therapy for autoimmune and inflammatory diseases. Nat Rev Immunol. 2015 May;15(5):283-94. doi: 10.1038/nri3823. Epub 2015 Apr 17.
- Background: PubMed 22129253Saadoun D, Rosenzwajg M, Joly F, Six A, Carrat F, Thibault V, Sene D, Cacoub P, Klatzmann D. Regulatory T-cell responses to low-dose interleukin-2 in HCV-induced vasculitis. N Engl J Med. 2011 Dec 1;365(22):2067-77. doi: 10.1056/NEJMoa1105143.
- Background: PubMed 24622415Hartemann A, Bensimon G, Payan CA, Jacqueminet S, Bourron O, Nicolas N, Fonfrede M, Rosenzwajg M, Bernard C, Klatzmann D. Low-dose interleukin 2 in patients with type 1 diabetes: a phase 1/2 randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2013 Dec;1(4):295-305. doi: 10.1016/S2213-8587(13)70113-X. Epub 2013 Oct 8.
- Background: PubMed 25634360Rosenzwajg M, Churlaud G, Mallone R, Six A, Derian N, Chaara W, Lorenzon R, Long SA, Buckner JH, Afonso G, Pham HP, Hartemann A, Yu A, Pugliese A, Malek TR, Klatzmann D. Low-dose interleukin-2 fosters a dose-dependent regulatory T cell tuned milieu in T1D patients. J Autoimmun. 2015 Apr;58:48-58. doi: 10.1016/j.jaut.2015.01.001. Epub 2015 Jan 26.
- Background: PubMed 24872229Castela E, Le Duff F, Butori C, Ticchioni M, Hofman P, Bahadoran P, Lacour JP, Passeron T. Effects of low-dose recombinant interleukin 2 to promote T-regulatory cells in alopecia areata. JAMA Dermatol. 2014 Jul;150(7):748-51. doi: 10.1001/jamadermatol.2014.504.
- Background: PubMed 25609413Humrich JY, von Spee-Mayer C, Siegert E, Alexander T, Hiepe F, Radbruch A, Burmester GR, Riemekasten G. Rapid induction of clinical remission by low-dose interleukin-2 in a patient with refractory SLE. Ann Rheum Dis. 2015 Apr;74(4):791-2. doi: 10.1136/annrheumdis-2014-206506. Epub 2015 Jan 21. No abstract available.
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Proleukin in people with Encephalitis, run by Seoul National University Hospital.
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 5 inclusion and 8 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 29 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Change of modified Rankin scale (time frame: Week 0,12). 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 NCT02714959, which also lists 6 linked publications.
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 29 Sep 2021.