IL-2 in Refractory Autoimmune Encephalitis
Study Details
Study Description
Brief Summary
The purpose of this study is to determine whether low-dose IL-2 is effective in refractory autoimmune encephalitis.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
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
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Proleukin 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 |
Drug: Proleukin
|
Outcome Measures
Primary Outcome Measures
- Change of modified Rankin scale [Week 0,12]
Secondary Outcome Measures
- The change of percentage of regulatory T (Treg) cells [Week 1, 3, 5, 9, 12, 21]
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [Week 1, 3, 5, 9, 12, 21]
- Quality of Life in Epilepsy Inventory (QOLIE)-31 [Week 21]
Quality of Life in Epilepsy Inventory (QOLIE)-31
- Beck Depression Inventory (BDI) [Week 21]
Beck Depression Inventory (BDI)
- Cognitive function [Week 21]
Mini-mental state examination (MMSE)
Eligibility Criteria
Criteria
Inclusion Criteria:
-
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)
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Refractory to first-line (high-dose steroid or intravenous immunoglobulin) and second line (rituximab or cyclophosphamide) immunotherapy
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Written informed consent form.
Exclusion Criteria:
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low hemoglobin <8.0 g/dL, absolute neutrophil count<1600/mm3, lymphocytes <600/mm3, platelets <140,000/mm3
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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
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Significant abnormality in chest X-ray other than these linked to the diseases under investigation
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Infection
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Other progressive neurological degenerative disease.
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Poor venous access not allowing repeated blood tests
-
pregnant or lactating women
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Seoul National University Hospital
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
- Castela 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.
- Hartemann 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.
- Humrich 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.
- 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. Review.
- Rosenzwajg M, Churlaud G, Mallone R, Six A, Dérian 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.
- Saadoun 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. Erratum in: N Engl J Med. 2014 Feb 20;370(8):786.
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