IL-2 in Refractory Autoimmune Encephalitis

Encephalitis Clinical Trial

Official title:

Effect of IL-2 in Refractory Autoimmune Encephalitis Patients: A Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02714959
• Other study ID #: 1510112713
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 2016
• Est. completion date: June 12, 2019

Study information

• Verified date: September 2021
• Source: Seoul National University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether low-dose IL-2 is effective in refractory autoimmune encephalitis.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: June 12, 2019
• Est. primary completion date: June 12, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years to 80 Years

Eligibility

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), a-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.

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Encephalitis

Intervention

Drug:
• Proleukin

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Seoul National University Hospital

References & Publications (6)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change of modified Rankin scale		Week 0,12
Secondary	The change of percentage of regulatory T (Treg) cells		Week 1, 3, 5, 9, 12, 21
Secondary	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0		Week 1, 3, 5, 9, 12, 21
Secondary	Quality of Life in Epilepsy Inventory (QOLIE)-31	Quality of Life in Epilepsy Inventory (QOLIE)-31	Week 21
Secondary	Beck Depression Inventory (BDI)	Beck Depression Inventory (BDI)	Week 21
Secondary	Cognitive function	Mini-mental state examination (MMSE)	Week 21