Intralymphatic Allergen Immunotherapy (ILIT) in grass pollen allergy: a randomized controlled trial

The primary objective is to assess the efficacy and safety of intralymphatic allergen immunotherapy (ILIT) in adolescents and adults with allergic rhinoconjunctivitis, with or without asthma, due to grass pollen allergy, using currently available commercial allergen extracts for ILIT administration. This evaluation addresses the clinical need to determine whether ILIT represents a viable treatment modality for grass pollen-induced allergic disease, with both therapeutic benefit and tolerability being critical considerations for clinical implementation.

The secondary objective focuses on investigating biological effects of ILIT in the study population. The assessment includes effects on mast cell-bound specific IgE and circulating unbound specific IgE, reflecting the known capacity of allergen immunotherapy to modify IgE-mediated immune responses to allergens. Total IgE levels will be measured. Additionally, serum allergen-specific IgG4 levels will be assayed as a predictor of clinical response to treatment, providing insight into immunological mechanisms underlying therapeutic outcomes.

The sponsor did not provide information regarding the total number of participants for this clinical trial. The study population includes **adults** aged **18 years or older** of both **male** and **female** gender. Participants are individuals diagnosed with **moderate to severe allergic rhino-conjunctivitis** due to **grass pollen**, with or without **asthma**. The trial involves a **vulnerable population**. Eligible participants must have a documented history of moderate-to-severe **allergic rhinitis** during the previous **pollen season**, confirmed through positive **skin prick test** results showing a wheal at least 3 mm larger than the negative control, and circulating **specific IgE** levels of at least 0.5 kU/l to grass pollen. Participants are required to have experienced significant symptoms during the prior season, evidenced by a **Symptom Score** of 7 or higher, or a self-reported retrospective **visual analogue scale** rating of nasal and/or ocular symptoms of at least 4 out of 10 cm during the peak symptom period of April through June.

This is a **randomized controlled trial** evaluating the efficacy and safety of **intralymphatic allergen immunotherapy** in adolescents and adults with **allergic rhino-conjunctivitis**, with or without **asthma**, caused by **grass pollen**. The trial employs commercially available **allergen extracts** administered via the **intralymphatic route**. The investigational medicinal product, designated as Anallergo, is administered at a maximum daily dose of 1 ml and a maximum total dose of 3 ml over a treatment period of 12 weeks. **Sodium chloride** 9 mg/1000 ml serves as the **placebo** comparator in this study. The trial is classified as a **Phase IV** study designed to assess therapeutic efficacy and adverse effects in larger patient populations.

Eligible participants include patients aged 18 years or older diagnosed with moderate to severe **allergic rhino-conjunctivitis** according to **ARIA** criteria. Diagnosis must be confirmed through a positive **skin prick test** with a wheal at least 3 mm larger than the negative control and circulating **specific IgE** levels of at least 0.5 kU/l to grass pollen. Participants must have a documented history of moderate-to-severe allergic rhinitis during the previous pollen season, evidenced by a **Symptom Score** of 7 or higher at screening, or alternatively, a self-reported retrospective **visual analogue scale** rating of nasal and/or ocular symptoms of 4/10 cm or higher. This retrospective assessment refers to the two-week period of peak symptom severity during the previous season between April and June. All participants must provide signed and dated **informed consent** approved by the **Institutional Review Board** or **Independent Ethics Committee**.

The primary endpoints of the trial include **symptom scores** ranging from 0 to 18 points, encompassing three nasal symptoms (runny nose, blocked nose, sneezing) and three ocular symptoms (red eyes, itchy eyes, watery eyes), each scored from 0 (no symptoms) to 3 (severe symptoms). Additional primary endpoints comprise **medication scores** that account for the exact number of **antihistamine** tablets, **nasal corticosteroid** puffs, and eye drops used, as well as the **Rhino-conjunctivitis Quality of Life Questionnaire**. These outcome measures are designed to comprehensively evaluate both clinical efficacy and impact on patient quality of life.

The trial is estimated to commence participant recruitment on October 1, 2025, with an anticipated completion date of September 30, 2026. The overall trial duration encompasses the recruitment period, treatment phase, and follow-up assessments necessary to capture pollen season symptom data. Participant involvement extends through the treatment period of 12 weeks and subsequent follow-up visits during the relevant pollen season to assess clinical outcomes. The study protocol may include provisions for early termination of individual participants based on predefined criteria, though specific conditions are determined according to safety monitoring protocols and participant withdrawal consent.

The experimental treatment consists of an allergen extract for intralymphatic allergen immunotherapy designated by the sponsor product code **Anallergo**. This investigational medicinal product is classified under **ATC code V04CL** (tests for allergic diseases) and is administered via the **intralymphatic route**. The pharmaceutical form is identified as PHF00024MIG. The dosing regimen involves a **maximum daily dose** of 1 ml (milliliter), with a **maximum total dose** of 3 ml administered over the course of treatment. The **maximum treatment period** is 12 weeks. This allergen extract represents the active intervention in participants with **allergic rhinoconjunctivitis** due to **grass pollen allergy**, with or without **asthma**.

The comparator treatment utilized in this study is **sodium chloride 9 mg/1000 ml**, which serves as the **placebo** control. This solution functions as an inert substance to enable blinding and comparison against the experimental allergen immunotherapy. The placebo is administered to the control group to assess the efficacy and safety of the investigational treatment relative to a non-active intervention.

Efficacy will be assessed through three primary endpoints. **Symptom scores** will be evaluated, ranging from 0 to 18 points, encompassing 3 nasal symptoms (runny nose, blocked nose, sneezing) and 3 ocular symptoms (red eyes, itchy eyes, watery eyes), with each symptom scored from 0 (no symptoms) to 3 (severe symptoms). **Medication scores** will be recorded by documenting the exact number of anti-histamine tablets, nasal corticosteroid puffs, and eye drops used. The **Rhino-conjunctivitis Quality of Life Questionnaire** will be administered to assess the impact of **allergic rhino-conjunctivitis** on patient quality of life. These parameters will be used to evaluate the efficacy of **intralymphatic allergen immunotherapy** in adolescents and adults with allergic rhino-conjunctivitis, with or without asthma, due to **grass pollen allergy**.