Allergic Rhinoconjunctivitis to Birch PollenPhase 2Rhinil-2NCT03776643
Safety and Efficacy of Low-dose IL-2 in Birch Pollen Allergy
A Phase 2 study testing ILT-101 ld-(IL2) in people with Allergic Rhinoconjunctivitis to Birch Pollen and With a Positive Skin Prick Test to Birch Pollen, run by Assistance Publique - Hôpitaux de Paris at 2 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Allergic Rhinoconjunctivitis to Birch Pollen, With a Positive Skin Prick Test to Birch Pollen
- What is being tested?
- ILT-101 ld-(IL2)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 2 sitesFrance
- Study dates
- 1 Feb 2019to 16 Aug 2022
- Phase
- Phase 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 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- male or female aged between18-55 years
- Positive clinical history of seasonal allergic rhinitis to birch pollen for at least 2 consecutive pollinic seasons before inclusion and requiring medication intake with or without GINA 1 associated asthma, with documentation of sensitivity within 12 months before enrollment by : *Positive skin prick test (SPT) and validated in vitro tests for specific Immunoglobulin E (IgE); *Positive Skin prick test (SPT): wheal for birch pollen ≥ 5 mm in diameter for histamine wheal ≥ 3 mm (positive control) and NaCl reaction < 2 mm (negative control) *Positive specific IgE to birch pollen >0.75 kUI/L;
- Negative beta-HcG pregnancy test at screening visit for women of childbearing age;
- Normal electrocardiogram without clinically significant abnormalities;
- Ability to stay in the EEC for up to 4 hours, without any conditions or factors which could make this not possible
- Positive nasal response (TNSS≥5) at baseline exposure
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- Free, informed and written consent signed by the patient and the investigator, before any specific examination required by the study;
- Affiliation to a social security scheme (beneficiary or assignee)
- Negative SARS-CoV-2 test less than 72 hours prior to screening visit
Who cannot join
- 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;
Show all 28Show fewer
- 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;
Trial locations and contacts
2 sites in 1 country.
France2 sites
CIC Biothérapies - Service de Biothérapies
Paris, Groupe Hospitalier Pitié-Salpêtrière 47 -83 BD de L'hopital, 75013
Centre d'essais cliniques, ALYATEC
Strasbourg, Environmental Exposure Chamber, Alyatec, 1 Place de L'hôpital, 67000
About this study
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.
Read the 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)
- Conditions
- Allergic Rhinoconjunctivitis to Birch Pollen, With a Positive Skin Prick Test to Birch Pollen
- Being tested
- ILT-101 ld-(IL2)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ILT-101 ld-(IL2)Drug
Also called Placebo
Subcutaneous injections of ILT-101 or Placebo starting with once-daily administration for 5 consecutive days followed by once every two weeks administration during five months
| Study group | Role | What they receive |
|---|---|---|
| ILT-101 (ld-IL2) | Experimental | Subcutaneous injections of ILT-101 Receives: Drug: ILT-101 ld-(IL2) |
| placebo | Placebo comparator | Subcutaneous injections of placebo Receives: Drug: ILT-101 ld-(IL2) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in nasal congestion expressed as area under the curve (AUC), during birch allergen exposure in ALYATEC's Environmental Exposure Chamber (EEC)
Change in nasal congestion expressed as area under the curve (AUC), during birch allergen exposure in ALYATEC's Environmental Exposure Chamber (EEC)
Measured: on day 40
Secondary outcomes (30)
Change in nasal congestion expressed as area under the curve (AUC), assessed during 4 hours of exposure
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)
Measured: at Day 8
Change in nasal response intensity
determined by Visual Analogue Scale (VAS) ranged from 0 to 10 cm where higher values correspond to more intense symptoms
Measured: at Day 8
Changes in Tregs expressed in percentag (%)
Changes in Tregs in percentag compared to baseline
Measured: at day 8
Changes in Tregs expressed in percentag (%)
Changes in Tregs in percentag compared to baseline
Measured: at day 40
Changes in Tregs expressed in percentag (%)
Changes in Tregs in percentag compared to baseline
Measured: at day 70
Changes in absolute count in Tregs
Changes in absolute count in Tregs compared to baseline
Measured: at day 8
Changes in absolute count in Tregs
Changes in absolute count in Tregs compared to baseline
Measured: at day 40
Changes in absolute count in Tregs
Changes in absolute count in Tregs compared to baseline
Measured: at day 70
Changes in eosinophils expressed in percentag (%)
Changes in eosinophils in percentag compared to baseline
Measured: at day 8
Changes in eosinophils expressed in percentag (%)
Changes in eosinophils in percentag compared to baseline
Measured: at day 40
Changes in eosinophils expressed in percentag (%)
Changes in eosinophils in percentag compared to baseline
Measured: at day 70
Changes in absolute count in eosinophils
Changes in absolute count in eosinophils compared to baseline
Measured: at day 8
Changes in absolute count in eosinophils
Changes in absolute count in eosinophils compared to baseline
Measured: at day 40
Changes in absolute count in eosinophils
Changes in absolute count in eosinophils compared to baseline
Measured: at day 70
Changes in Inate Lymphoid Cell type 2(ILC2) expressed in percentag (%)
Changes in Inate Lymphoid Cell type 2 in percentag compared to baseline
Measured: at day 8
Changes in Inate Lymphoid Cell type 2(ILC2) expressed in percentag (%)
Changes in Inate Lymphoid Cell type 2 in percentag compared to baseline
Measured: at day 40
Changes in Inate Lymphoid Cell type 2(ILC2) expressed in percentag (%)
Changes in Inate Lymphoid Cell type 2 in percentag compared to baseline
Measured: at day 70
Changes in absolute count in Inate Lymphoid Cell type 2(ILC2)
Changes (in absolute count in Inate Lymphoid Cell type 2 compared to baseline
Measured: at day 8
Changes in absolute count in Inate Lymphoid Cell type 2(ILC2)
Changes (in absolute count in Inate Lymphoid Cell type 2 compared to baseline
Measured: at day 40
Changes in absolute count in Inate Lymphoid Cell type 2(ILC2)
Changes (in absolute count in Inate Lymphoid Cell type 2 compared to baseline
Measured: at day 70
Changes of antigen-specific T-cell immune responses (cytokine IL-4 )
cytokine IL-4 at day 40
Measured: at day 40
Changes of antigen-specific T-cell immune responses (cytokine IL-4 )
cytokine IL-4 at day 70
Measured: at day 70
Changes of antigen-specific T-cell immune responses (cytokine IL-5)
cytokine IL-5 at day 40
Measured: at day 40
Changes of antigen-specific T-cell immune responses (cytokine IL-5)
cytokine IL-5 at day 70
Measured: at day 70
Changes of antigen-specific T-cell immune responses
IL-13 secretion after antigen restimulation at day 40
Measured: at day 40
Changes of antigen-specific T-cell immune responses
IL-13 secretion after antigen restimulation at day 70
Measured: at day 70
Changes in allergen-specific IgE dosages basophil activation test with pollen allergen
allergen-specific IgE dosages at day 40
Measured: at day 40
Incidence of adverse events at day 8
Adverse events throughout the study (according to NCI-CTC AE classification)
Measured: up to Day 8
Incidence of adverse events at day 40
Adverse events throughout the study (according to NCI-CTC AE classification)
Measured: up to Day 40
Incidence of adverse events at 70
Adverse events throughout the study (according to NCI-CTC AE classification)
Measured: up to Day 70
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2018
- Study start1 Feb 2019
- Primary completion16 Aug 2022
- Study completion16 Aug 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Allergic Rhinoconjunctivitis to Birch PollenStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Safety/Efficacy
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Iltoo Pharma
- Responsible party
- Sponsor
- Investigators
- David Klatzmann, Pr, Study chair, APHP / CIC BTI / Hopital Pitie Salpétrière, Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03776643
- Sponsor's protocol ID
- P160936J
- Acronym
- Rhinil-2
- Status last verified
- Dec 2022
- First submitted
- 20 Nov 2018
- Last updated
- 16 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Low-dose IL-2 in Birch Pollen Allergy
- ClinicalTrials.gov ID
- NCT03776643
- Acronym / sponsor ID
- Rhinil-2 / P160936J
- Conditions
- Allergic Rhinoconjunctivitis to Birch Pollen, With a Positive Skin Prick Test to Birch Pollen
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- Iltoo Pharma
- Study start
- 1 Feb 2019 (actual)
- Primary completion
- 16 Aug 2022 (actual)
- Study completion
- 16 Aug 2022 (actual)
- First posted
- 17 Dec 2018 (actual)
- 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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Safety/Efficacy
| Arm | Type | Receives |
|---|---|---|
| ILT-101 (ld-IL2) | Experimental | Drug: ILT-101 ld-(IL2)Subcutaneous injections of ILT-101 |
| placebo | Placebo comparator | Drug: ILT-101 ld-(IL2)Subcutaneous injections of placebo |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- male or female aged between18-55 years
- Positive clinical history of seasonal allergic rhinitis to birch pollen for at least 2 consecutive pollinic seasons before inclusion and requiring medication intake with or without GINA 1 associated asthma, with documentation of sensitivity within 12 months before enrollment by : *Positive skin prick test (SPT) and validated in vitro tests for specific Immunoglobulin E (IgE); *Positive Skin prick test (SPT): wheal for birch pollen ≥ 5 mm in diameter for histamine wheal ≥ 3 mm (positive control) and NaCl reaction < 2 mm (negative control) *Positive specific IgE to birch pollen >0.75 kUI/L;
- Negative beta-HcG pregnancy test at screening visit for women of childbearing age;
- Normal electrocardiogram without clinically significant abnormalities;
- Ability to stay in the EEC for up to 4 hours, without any conditions or factors which could make this not possible
Key exclusion criteria (28 listed)
- 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;
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 |
|---|---|---|
| ILT-101 ld-(IL2)Also: PlaceboSubcutaneous injections of ILT-101 or Placebo starting with once-daily administration for 5 consecutive days followed by once every two weeks administration during five months | Drug | ILT-101 (ld-IL2), placebo |
Primary outcome
Change in nasal congestion expressed as area under the curve (AUC), during birch allergen exposure in ALYATEC's Environmental Exposure Chamber (EEC)
Time frame: 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)
30 secondary outcomes
Change in nasal congestion expressed as area under the curve (AUC), assessed during 4 hours of exposure
Time frame: at Day 8
Change in nasal response intensity
Time frame: at Day 8
Changes in Tregs expressed in percentag (%)
Time frame: at day 8
Changes in Tregs expressed in percentag (%)
Time frame: at day 40
Changes in Tregs expressed in percentag (%)
Time frame: at day 70
Changes in absolute count in Tregs
Time frame: at day 8
Changes in absolute count in Tregs
Time frame: at day 40
Changes in absolute count in Tregs
Time frame: at day 70
Changes in eosinophils expressed in percentag (%)
Time frame: at day 8
Changes in eosinophils expressed in percentag (%)
Time frame: at day 40
Changes in eosinophils expressed in percentag (%)
Time frame: at day 70
Changes in absolute count in eosinophils
Time frame: at day 8
Changes in absolute count in eosinophils
Time frame: at day 40
Changes in absolute count in eosinophils
Time frame: at day 70
Changes in Inate Lymphoid Cell type 2(ILC2) expressed in percentag (%)
Time frame: at day 8
Changes in Inate Lymphoid Cell type 2(ILC2) expressed in percentag (%)
Time frame: at day 40
Changes in Inate Lymphoid Cell type 2(ILC2) expressed in percentag (%)
Time frame: at day 70
Changes in absolute count in Inate Lymphoid Cell type 2(ILC2)
Time frame: at day 8
Changes in absolute count in Inate Lymphoid Cell type 2(ILC2)
Time frame: at day 40
Changes in absolute count in Inate Lymphoid Cell type 2(ILC2)
Time frame: at day 70
Changes of antigen-specific T-cell immune responses (cytokine IL-4 )
Time frame: at day 40
Changes of antigen-specific T-cell immune responses (cytokine IL-4 )
Time frame: at day 70
Changes of antigen-specific T-cell immune responses (cytokine IL-5)
Time frame: at day 40
Changes of antigen-specific T-cell immune responses (cytokine IL-5)
Time frame: at day 70
Changes of antigen-specific T-cell immune responses
Time frame: at day 40
Changes of antigen-specific T-cell immune responses
Time frame: at day 70
Changes in allergen-specific IgE dosages basophil activation test with pollen allergen
Time frame: at day 40
Incidence of adverse events at day 8
Time frame: up to Day 8
Incidence of adverse events at day 40
Time frame: up to Day 40
Incidence of adverse events at 70
Time frame: up to Day 70
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 16 Sep 2025.
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.
David Klatzmann, Pr study chair
APHP / CIC BTI / Hopital Pitie Salpétrière, Paris
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ILT-101 ld-(IL2) in people with Allergic Rhinoconjunctivitis to Birch Pollen and With a Positive Skin Prick Test to Birch Pollen, run by Assistance Publique - Hôpitaux de Paris at 2 sites in France.
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 9 inclusion and 28 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 16 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
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 in nasal congestion expressed as area under the curve (AUC), during birch allergen exposure in ALYATEC's Environmental Exposure Chamber (EEC) (time frame: on day 40). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 Sep 2025.