Safety and Efficacy of Low-dose IL-2 in Birch Pollen Allergy

Phase 2

Completed

• Conditions: Allergic Rhinoconjunctivitis to Birch Pollen; With a Positive Skin Prick Test to Birch Pollen
• Interventions: Drug: ILT-101 ld-(IL2)

• Registration Number: NCT03776643
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

Several studies have reported a deficit and/or a defect in regulatory T cells in allergic subjects, which can be correlated with the allergic responses, especially for respiratory allergies. Low-dose IL-2 (ld-IL2) specifically targets and activates regulatory T cells (Tregs), which are cells that regulate immune responses. Thus by stimulating Tregs, ld-IL2 would control allergic responses.

This study is designed to evaluate the efficacy of ILT-101 (ld-IL-2), compared to placebo, on the nasal response assessed by Total Nasal Symptom Score (TNSS) during a controlled birch allergen exposure.

Detailed Description

Primary objective To evaluate the efficacy of ILT-101 (ld-IL-2), compared to placebo, on nasal response on day 40

Secondary objectives To evaluate the efficacy of ILT-101 on rhino-conjunctivitis symptoms, on inflammatory mediators, allergic specific immune responses and safety.

Experimental design This is a monocentric, randomized, placebo controlled, double-blind trial in parallel-groups, evaluating a treatment by ILT-101/placebo, 1 MIU daily for 5 days and 1 MIU every week, until day 36.

Population involved Male or female, aged between 18 and 55 years, with allergic rhinitis to birch pollen.

Number of subjects: 24

Duration of patient participation: 3 months (treatment period: 36 days months, follow-up period: 34 days)

Study Timeline

• Study First Submitted: 2018-11-20
• Study First Submitted QC: 2018-12-12
• Study First Posted: 2018-12-17
• Study Start: 2019-02-01
• Primary Completion: 2022-08-16
• Study Completion: 2022-08-16
• Status Verified: 2022-12
• Last Update Submitted: 2023-12-01
• Last Update Posted: 2023-12-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

Not provided

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Exclusion Criteria

• Asthma: GINA 2 to 5

• Eosinophilia > 0.6x109/mL;

• Any history of anaphylactic reactions;

• Specific immunotherapy treatment at the moment, including Omalizumab;

• Specific immunotherapy for birch-pollens within 3 previous years;

• Use of systemic corticosteroid or others immunosuppressive treatment within previous 6 months;

• Moderate to severe allergic rhinoconjunctivitis with or without asthma due to grass pollen, if the study is performed during grass pollen season (according to ARIA)

• Significant rhinitis, or sinusitis, due to daily contact with other allergen causing symptoms that are expected to coincide with exposures, as assessed by the investigator

• Contraindications known to treatment with IL-2:

  • Hypersensitivity to the active substance or to any of the excipients;
  • Immunosuppressed patient;
  • Psychotropic, hepatotoxic, nephrotoxic, myelotoxic or cardiotoxic drugs;
  • Other chronic diseases not clinically controlled;
  • Signs of active infection requiring treatment;
  • Previous history of organ transplantation.
  • Heart failure (≥ grade II, class. NYHA), kidney failure (Cockroft <60 ml/min/1.73m2), liver failure (transaminase> 3N), pulmonary insufficiency (any grade);

• Leukocytes <3000 / mm3 lymphocytes <800 / mm3, platelets <80 000 / mm3, Hemoglobin < 10.0 g/dL or 6.2 mmol/L, red cell blood < 3.5 T/L;

• Positivity of at least one of the thyroid-specific antibodies (anti-TPO, anti-TG, or anti-TRAKS) associated with an abnormal thyroid workup (TSH, T3, or T4) at inclusion;

• Chronic uncontrolled arterial hypertension (Systolic BP > 140 mmHg and/or Diastolic BP > 90 mmHg);

• Poor venous capital will forbid blood samples;

• Vaccination with attenuated live vaccine in the month before the inclusion or planned during the study;

• Vaccination against COVID-19 during the study period or if the 2nd dose of vaccine is planned during the 15 days preceding Visit 3

• Surgery in the previous three months or anticipated under study;

• Participation in other interventional research with study drug in the previous month and during the study;

• Psychiatric illness or any other concomitant chronic illness or addiction that could interfere with the ability to meet the requirements of the protocol or provide informed consent;

• Presence or history of unhealed cancer for more than five years, presence or history of healed cancer for less than five years, except carcinoma in situ of the cervix or basal cell carcinoma;

• Pregnant or lactating women;

• Men and women of childbearing age without effective contraception during the treatment period;

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ILT-101 (ld-IL2)	ILT-101 ld-(IL2)	Subcutaneous injections of ILT-101
placebo	ILT-101 ld-(IL2)	Subcutaneous injections of placebo

Primary Outcome Measures

Name	Time	Method
Change in nasal congestion expressed as area under the curve (AUC), during birch allergen exposure in ALYATEC's Environmental Exposure Chamber (EEC)	on day 40	Change in nasal congestion expressed as area under the curve (AUC), during birch allergen exposure in ALYATEC's Environmental Exposure Chamber (EEC)

Secondary Outcome Measures

Name	Time	Method
Change in nasal response intensity	at Day 8	determined by Visual Analogue Scale (VAS) ranged from 0 to 10 cm where higher values correspond to more intense symptoms
Changes in Tregs expressed in percentag (%)	at day 70	Changes in Tregs in percentag compared to baseline
Incidence of adverse events at 70	up to Day 70	Adverse events throughout the study (according to NCI-CTC AE classification)
Change in nasal congestion expressed as area under the curve (AUC), assessed during 4 hours of exposure	at Day 8	TNSS, expressed as area under the curve (AUC), assessed during 4 hours of exposure: TOTAL NASAL SYMPTOM SCORE Definition of response choices (drop down menu for each of the 4 questions below) 0 = None 1 = Mild (symptom clearly present but easily tolerated) 2 = Moderate (annoying but tolerable symptom) 3 = Severe (difficult to tolerate symptom, disrupts activities)
Changes in absolute count in Inate Lymphoid Cell type 2(ILC2)	at day 70	Changes (in absolute count in Inate Lymphoid Cell type 2 compared to baseline
Changes of antigen-specific T-cell immune responses	at day 70	IL-13 secretion after antigen restimulation at day 70
Changes of antigen-specific T-cell immune responses (cytokine IL-4 )	at day 70	cytokine IL-4 at day 70
Changes in absolute count in Tregs	at day 70	Changes in absolute count in Tregs compared to baseline
Changes in eosinophils expressed in percentag (%)	at day 70	Changes in eosinophils in percentag compared to baseline
Changes in absolute count in eosinophils	at day 70	Changes in absolute count in eosinophils compared to baseline
Changes in Inate Lymphoid Cell type 2(ILC2) expressed in percentag (%)	at day 70	Changes in Inate Lymphoid Cell type 2 in percentag compared to baseline
Incidence of adverse events at day 8	up to Day 8	Adverse events throughout the study (according to NCI-CTC AE classification)
Incidence of adverse events at day 40	up to Day 40	Adverse events throughout the study (according to NCI-CTC AE classification)
Changes of antigen-specific T-cell immune responses (cytokine IL-5)	at day 70	cytokine IL-5 at day 70
Changes in allergen-specific IgE dosages basophil activation test with pollen allergen	at day 40	allergen-specific IgE dosages at day 40

Trial Locations

Locations (2)

CIC Biothérapies - Service de Biothérapies; 🇫🇷 Paris, Groupe Hospitalier Pitié-Salpêtrière 47 -83 BD DE L'hopital, France

Centre d'essais cliniques, ALYATEC; 🇫🇷 Strasbourg, Environmental Exposure Chamber, Alyatec, 1 Place De L'hôpital, France