Efficacy of a polymerized mannan‑conjugated Phleum pratense and Dactylis glomerata allergoid vaccine in patients with grass‑pollen allergic rhinitis/rhinoconjunctivitis

The primary objective is to evaluate the grass pollen‑induced allergic rhinitis or rhinoconjunctivitis clinical response to two dose concentrations (3000 mTU/mL and 9000 mTU/mL) of the polymerised mannan‑conjugated allergoid Dactylis glomerata/Phleum pratense administered subcutaneously, with the aim of identifying the concentration that provides optimal efficacy while maintaining an acceptable safety and tolerability profile.

The trial enrolled adult individuals aged 18 to 64 years of both sexes who were in good physical and mental health. Participants were required to have a confirmed diagnosis of moderate to severe grass pollen‑induced allergic rhinitis or rhinoconjunctivitis based on a consistent medical history, positive skin‑prick test, and specific IgE ≥0.7 kU/L to Phleum pratense. Selection required normal renal and liver function (≤ grade 2 deviations) and, for women of childbearing potential, a negative pregnancy test and the use of highly effective contraception. Eligible subjects also needed controlled allergic (extrinsic) asthma or normal lung function (FEV₁ ≥ 80 % predicted). The sponsor did not provide information on the total number of participants.

The study is a prospective, multicentre, randomized, double‑blind, placebo‑controlled dose‑finding trial evaluating subcutaneous injections of a polymerised mannan‑conjugated allergoid (Phleum pratense/Dactylis glomerata) at two concentrations (3000 mTU/mL and 9000 mTU/mL) versus matching placebo in adults with grass pollen‑induced allergic rhinitis or rhinoconjunctivitis. Participants are screened (Visit 1) to confirm eligibility criteria, including specific IgE ≥0.7 kU/L, a positive skin‑prick test, and a negative pregnancy test for women of child‑bearing potential. Eligible subjects are then randomized to one of the three treatment arms and receive the first subcutaneous dose at the baseline visit (Visit 2). Subsequent follow‑up visits are scheduled at regular intervals (e.g., weeks 4, 8, 12, and 24) for additional dosing, safety monitoring, and collection of the Combined Symptom and Medication Score (CSMS) during the peak grass pollen season. The final end‑of‑study visit occurs after completion of the 2027 pollen season to assess the primary efficacy endpoint and overall tolerability. Participant involvement spans approximately 12–15 months from screening through the end‑of‑study visit. Early termination may occur if a participant withdraws consent, experiences a serious adverse event, develops a pregnancy, exhibits clinically significant laboratory abnormalities, or fails to adhere to the protocol schedule.

The investigational medicinal product is a polymerised mannan‑conjugated allergoid containing Phleum pratense and Dactylis glomerata pollen extracts. It is supplied as a sterile solution for subcutaneous injection. Two dose concentrations are evaluated in the trial: 3000 mTU/mL and 9000 mTU/mL. Each dose is administered by a single‑use syringe according to the study‑specified schedule, and all administrations are performed by qualified study personnel.

The control arm receives a placebo that is identical in appearance, volume, and packaging to the active vaccine. The placebo is also delivered by subcutaneous injection using the same administration schedule as the active product.

Rescue and concomitant medications permitted during the study include a range of antihistamines, nasal corticosteroids, and ocular antihistamine drops. These agents may be used according to standard clinical practice to manage symptoms of allergic rhinitis or rhinoconjunctivitis. Examples are:

• Bilastine 20 mg oral tablet
• Desloratadine 5 mg oral tablet
• Fexofenadine 180 mg oral tablet
• Loratadine 10 mg oral tablet
• Rupatadine 10 mg oral tablet
• Ebastine 10 mg oral tablet
• Allegra (Bilastine) 20 mg oral tablet
• Mometasone furoate nasal spray 200 µg per dose
• Budesonide nasal spray 256 µg per dose
• Fluticasone propionate nasal spray 160 µg per dose
• Triamcinolone acetonide nasal spray 220 µg per dose
• Fluticasone furoate nasal spray 110 µg per dose
• Az­elastine eye drops 0.06 mg per dose
• Bilastine eye drops 0.2 µg per dose
• Olopatadine eye drops 0.2 mg per dose
• Emedastine eye drops 0.1 mg per dose
• Levocabastine eye drops 0.06 mg per dose
• Ciclesonide inhalation solution 160 µg per dose

Compliance with the investigational product dosing is documented in the study treatment log, and each injection is verified by the administering clinician. Use of rescue medications is recorded in the patient diary to allow assessment of concomitant therapy throughout the trial.

Efficacy will be evaluated by determining the Combined Symptom and Medication Score (CSMS) for each participant. The CSMS will be calculated daily according to the EAACI position paper (Pfaar et al., 2014) and averaged over the peak grass pollen season of 2027. Daily symptom and medication data will be recorded throughout the season, aggregated, and the mean daily CSMS will be derived for each treatment group. Comparative statistical analysis of the mean CSMS between the two active concentrations and placebo will be performed to identify the concentration with the greatest clinical efficacy.