Proleukin low dose (aldesleukin low dose) / ILTOO, Servier - LARVOL DELTA

Efficacy and Safety of Low-Dose Interleukin-2 Therapy in Systemic Lupus Erythematosus: A Systematic Review. (PubMed, Cureus) - "Ld-IL-2 therapy appears to be a safe and effective immunomodulatory treatment for patients with SLE, capable of enhancing Treg function and reducing disease activity. While current evidence is encouraging, larger multicenter randomized trials are warranted to establish standardized treatment protocols and validate predictive biomarkers for optimized patient selection."

IO biomarker • Journal • Review • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • CD4 • PD-1

Expression of an interleukin-2 partial agonist enhances regulatory T cell persistence and efficacy in mouse autoimmune models. (PubMed, Nat Commun) - "Lastly, compared with control Treg, human Tregs-IL2pa show enhanced survival in the IL-2-depleted environment of immune-deficient mice and improved control of xenogeneic graft-versus-host disease. Our results thus show that IL-2pa self-sufficiency enhances the stability, durability and efficacy of Treg therapies in preclinical settings."

Journal • Preclinical • Graft versus Host Disease • Immunology • Inflammation • IL2

Aulos Bioscience Doses First Patient in Phase 2 Cohort Evaluating the Combination of Avelumab and AU-007 for the Treatment of Non-Small Cell Lung Cancer (Businesswire) - "Aulos Bioscience...announced dosing of the first patient with AU-007, avelumab, a PD-L1 antibody with Fc effector function, and low-dose, subcutaneous aldesleukin in a Phase 2 cohort focused on the second-line treatment of PD-L1+ non-small cell lung cancer (NSCLC). The Phase 2 cohort is a clinical trial collaboration with Ares Trading S.A., a Swiss subsidiary of Merck KGaA, Darmstadt, Germany, and part of Aulos’ Phase 1/2 clinical trial of AU-007....The AU-007 Phase 1/2 study is currently enrolling patients with unresectable locally advanced or metastatic cancer at multiple clinical trial site locations in the United States and Australia....Aulos plans to share preliminary data from the Phase 2 cohort studying AU-007 with avelumab and low-dose, subcutaneous aldesleukin as a second-line treatment for PD-L1+ NSCLC in the first half of 2025."

P2 data • Trial status • Non Small Cell Lung Cancer

DF-IL2-REP: Ciclosporin Followed by Low-dose IL-2 in Patients with Recently Diagnosed Type 1 Diabetes (clinicaltrials.gov) - P2 | N=24 | Recruiting | Sponsor: Assistance Publique - Hôpitaux de Paris | Trial completion date: Jul 2026 ➔ Apr 2028 | Trial primary completion date: Oct 2024 ➔ Apr 2026

Trial completion date • Trial primary completion date • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

A Comprehensive Review of Low-Dose Interleukin-2 (IL-2) Therapy for Systemic Lupus Erythematosus: Mechanisms, Efficacy, and Clinical Applications. (PubMed, Cureus) - "A thorough review of clinical studies finds that low-dose IL-2 treatment is well-tolerated and effective, with fewer side effects than biologics like belimumab and rituximab...Future research should prioritize refining dose regimes, discovering biomarkers for patient selection, and investigating combination medicines. Addressing these issues might solidify low-dose IL-2 treatment as a cornerstone in SLE care, providing a more accurate and individualized approach to immune regulation while considerably improving patient outcomes."

Journal • Review • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

[PREPRINT] Low-dose interleukin-2 in patients with bipolar depression: a phase 2 randomised double-blind placebo-controlled trial (medRxiv) - P2 | N=15 | DEPIL-2 (NCT04133233) | "The primary evaluation criterion was met, with IL-2LD expanding 1.17 [95% CI 1.01- 1.34] vs 1.01 [95% CI 0.90 - 1.12] (p=0.0421) and activating Tregs. Secondary evaluation criteria were also met with significant improvements of depressive symptoms and global functioning from day-15 onwards in the IL-2LD treated patients. The treatment was well-tolerated, with no serious adverse events related to treatment. This proof-of-concept trial shows that stimulating Tregs in patients with bipolar depression is safe and associated with clinical improvements."

P2 data • Preprint • Bipolar Disorder • CNS Disorders • Depression

FaCIL-2: Low-dose Interleukin-2 in Women With Unexplained Miscarriages (clinicaltrials.gov) - P1/2 | N=18 | Completed | Sponsor: Assistance Publique - Hôpitaux de Paris | Active, not recruiting ➔ Completed

Trial completion • CD4 • IL2

FaCIL-2: Low-dose Interleukin-2 in Women With Unexplained Miscarriages (clinicaltrials.gov) - P1/2 | N=18 | Active, not recruiting | Sponsor: Assistance Publique - Hôpitaux de Paris | Trial primary completion date: Feb 2024 ➔ Jul 2023 | Trial completion date: Feb 2025 ➔ Apr 2024

Trial completion date • Trial primary completion date • CD4 • IL2

The universal effects of low-dose interleukin-2 across 13 autoimmune diseases in a basket clinical trial. (PubMed, J Autoimmun) - "Tregs stimulation by IL-2LD is a promising therapeutic strategy and IL-2LD holds considerable promise for integration into combinatorial therapeutic approaches."

Journal • Ankylosing Spondylitis • Dermatology • Fibrosis • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Rare Diseases • Rheumatology • Scleroderma • Seronegative Spondyloarthropathies • Sjogren's Syndrome • Systemic Lupus Erythematosus • Systemic Sclerosis • Urticaria

Low-dose IL-2 in Established T1D - The "PROREG" Study (clinicaltrials.gov) - P1/2 | N=0 | Withdrawn | Sponsor: Jay S. Skyler

Trial completion date • Trial primary completion date • Diabetes • Immunology • Metabolic Disorders • Type 1 Diabetes Mellitus

Low-dose interleukin-2 therapy in systemic lupus erythematosus. (PubMed, Rheumatol Immunol Res) - "This review discusses the rationale for the use of low-dose IL-2 therapy in SLE, the clinical responses in patients, and the effects of this therapy on different types of T cells. Considerations are made on the current and future directions of use of low-dose IL-2 regimens in SLE."

Journal • Review • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

DF-IL2-REP: Ciclosporin Followed by Low-dose IL-2 in Patients With Recently Diagnosed Type 1 Diabetes (clinicaltrials.gov) - P2 | N=24 | Recruiting | Sponsor: Assistance Publique - Hôpitaux de Paris | Trial completion date: Jul 2025 ➔ Jul 2026 | Trial primary completion date: Oct 2023 ➔ Oct 2024

Trial completion date • Trial primary completion date • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus • CD4

DEPIL-2: Low Dose IL-2 Therapy in Patients With a Depressive Episode in the Course of a Bipolar Disorder (clinicaltrials.gov) - P2 | N=15 | Completed | Sponsor: Assistance Publique - Hôpitaux de Paris | Recruiting ➔ Completed

Trial completion • Bipolar Disorder • CNS Disorders • Depression • Mood Disorders • Psychiatry • CD4 • IL2

FaCIL-2: Low-dose Interleukin-2 in Women With Unexplained Miscarriages (clinicaltrials.gov) - P1/2 | N=18 | Active, not recruiting | Sponsor: Assistance Publique - Hôpitaux de Paris | Recruiting ➔ Active, not recruiting | N=10 ➔ 18

Enrollment change • Enrollment closed • CD4 • IL2

Safety and efficacy of low- dose IL- 2 in birch pollen allergy (EAACI 2023) - "Conclusion ILT-101 induces a significant increase of Treg in humans and tends to decrease rhinitis symptoms. EEC is a good model to evaluate the efficacy of a drug on rhinitis symptoms in allergic patients."

Clinical • Allergic Rhinitis • Allergy • Immunology • Inflammation

Rhinil-2: Safety and Efficacy of Low-dose IL-2 in Birch Pollen Allergy (clinicaltrials.gov) - P2 | N=24 | Completed | Sponsor: Assistance Publique - Hôpitaux de Paris | Recruiting ➔ Completed | Trial completion date: Mar 2024 ➔ Aug 2022

Trial completion • Trial completion date • Allergy • Conjunctivitis • Immunology • Ocular Infections • Ocular Inflammation • Ophthalmology • IL4 • IL5

DEPIL-2: Low Dose IL-2 Therapy in Patients With a Depressive Episode in the Course of a Bipolar Disorder (clinicaltrials.gov) - P2 | N=18 | Recruiting | Sponsor: Assistance Publique - Hôpitaux de Paris | Trial completion date: Aug 2022 ➔ Apr 2023 | Trial primary completion date: Jun 2022 ➔ Feb 2023

Trial completion date • Trial primary completion date • Bipolar Disorder • CNS Disorders • Depression • Mood Disorders • Psychiatry • CD4 • IL2

DF-IL2-REP: Ciclosporin Followed by Low-dose IL-2 in Patients With Recently Diagnosed Type 1 Diabetes (clinicaltrials.gov) - P2 | N=24 | Recruiting | Sponsor: Assistance Publique - Hôpitaux de Paris | Not yet recruiting ➔ Recruiting | Trial completion date: Dec 2024 ➔ Jul 2025 | Trial primary completion date: Mar 2023 ➔ Oct 2023

Enrollment open • Trial completion date • Trial primary completion date • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus • CD4

Low-dose interleukin-2 therapy in active systemic lupus erythematosus (LUPIL-2): a multicentre, double-blind, randomised and placebo-controlled phase II trial. (PubMed, Ann Rheum Dis) - P2 | "The post hoc hierarchical analysis of the primary and key secondary end points in a per-protocol population, complemented by the exploratory analyses of multiple other secondary end points, support that low-dose IL-2 is beneficial in active SLE."

Journal • P2 data • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

Emerging mechanisms and applications of low-dose IL-2 therapy in autoimmunity. (PubMed, Cytokine Growth Factor Rev) - "This article will review major recent advances in fundamental research on IL-2 as well as significant progress made in clinical trials where patients received low-dose IL-2 therapy. This knowledge also helps design further optimized IL-2 therapies for a broader application in treating human disease."

Journal • Review • Immune Modulation • Immunology • Infectious Disease • Inflammation • Inflammatory Arthritis • Lupus • Oncology • CD8

Low Dose IL-2 Efficacy in Rheumatoid Arthritis (RheumNow) - P=NA | N=40 | "A novel biologic intervention trial has shown that subcutaneous, intermittent therapy with low-dose interleukin-2 (Ld-IL2) is potentially effective and safe in rheumatoid arthritis (RA)....These results suggested that Ld-IL2 in RA merits further study."

Clinical data

Rhinil-2: Safety and Efficacy of Low-dose IL-2 in Birch Pollen Allergy (clinicaltrials.gov) - P2 | N=24 | Recruiting | Sponsor: Assistance Publique - Hôpitaux de Paris | Suspended ➔ Recruiting | Trial completion date: Apr 2022 ➔ Mar 2024 | Trial primary completion date: Dec 2021 ➔ Aug 2022

Enrollment open • Trial completion date • Trial primary completion date • Allergy • Conjunctivitis • Immunology • Ocular Infections • Ocular Inflammation • Ophthalmology • IL4 • IL5

HEALTHIL-2: Low-dose IL-2 to the Kinetics of Regulatory T-cell in Healthy Volunteers (clinicaltrials.gov) - P1; N=40; Completed; Sponsor: Assistance Publique - Hôpitaux de Paris; Recruiting ➔ Completed; Trial completion date: Mar 2022 ➔ Nov 2021

Clinical • Trial completion • Trial completion date • CD4 • IL2

Rhinil-2: Safety and Efficacy of Low-dose IL-2 in Birch Pollen Allergy (clinicaltrials.gov) - P2; N=24; Suspended; Sponsor: Assistance Publique - Hôpitaux de Paris; N=50 ➔ 24; Trial completion date: Jun 2020 ➔ Apr 2022; Recruiting ➔ Suspended; Trial primary completion date: Oct 2019 ➔ Dec 2021

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Trial suspension • Allergy • Conjunctivitis • Immunology • Ocular Infections • Ocular Inflammation • Ophthalmology • IL4 • IL5

Low-dose IL-2 in Established T1D - The "PROREG" Study (clinicaltrials.gov) - P1/2; N=0; Withdrawn; Sponsor: Jay S. Skyler; N=60 ➔ 0; Suspended ➔ Withdrawn

Clinical • Enrollment change • Trial withdrawal • Diabetes • Immunology • Metabolic Disorders • Type 1 Diabetes Mellitus