Efficacy and safety of grass and olive pollen extract combination therapy versus placebo in patients with allergic rhinoconjunctivitis and asthma

The primary objective is to evaluate the clinical efficacy of grass and olive allergen immunotherapy compared to a placebo in patients with allergic rhinoconjunctivitis with or without asthma caused by sensitization to grass and olive pollen. Efficacy is assessed through a combined symptom and medication score during the peak pollination period following at least 8 injections. The secondary objectives include:

• Assessment of clinical efficacy, quality of life, treatment satisfaction, and immunological parameters throughout the entire grass and olive pollen season.
• Evaluation of the efficacy of immunotherapy specifically within the asthma patient subset during the pollen peak and throughout the pollen season.

The sponsor did not provide information regarding the total number of participants. The study population consists of patients with allergic rhinoconjunctivitis, which may include those with asthma resulting from sensitization to grass and olive pollen. Eligible individuals are aged 6 years or older. Participants with asthma must have controlled disease according to GINA guidelines, no severe asthma exacerbations in the previous pollen season, and a forced expiratory volume in 1 second of at least 70%. The population includes both male and female subjects and encompasses vulnerable groups. Inclusion requires the ability to maintain a residence during the pollen season and the use of a mobile device for symptom monitoring. Preexisting stable disease is permitted if no significant therapeutic changes or hospitalizations occurred within 28 days prior to enrollment.

This Phase 5 clinical trial is designed to evaluate the efficacy and safety of Depigoid DUO Grass-Mix/Olea compared to a placebo in patients diagnosed with allergic rhinoconjunctivitis with or without asthma resulting from sensitization to grass and olive pollen. The study utilizes a comparative design to assess the clinical efficacy of allergen immunotherapy. Participants will undergo a screening process to confirm eligibility based on criteria such as age, disease severity, and controlled asthma status. Following enrollment, the investigational medicinal product is administered via subcutaneous injection. The primary endpoint is the assessment of the combined symptom and medication score via a mobile application during the peak pollination period after a minimum of 8 injections. The trial involves monitoring participants throughout the grass and olive pollen seasons. Early termination from the study may occur based on investigator judgment or safety considerations. Total participant involvement is linked to the duration of the pollen seasons within the trial period, which is estimated to conclude by July 2029.

The investigational medicinal product is Depigoid DUO Grass-Mix/Olea (1000 DPP/ml + 1000 DPP/ml), provided as a suspension for injection. This product contains depigmented polymerized extract of Olea europaea pollen, Phleum pratense pollen, Festuca elatior pollen, Dactylis glomerata pollen, Poa pratensis pollen, and Lolium perenne pollen. The administration route is subcutaneous injection at a dose of 0.5 ml.

The placebo consists of the solvent utilized in the formulation of the investigational medicinal product, resulting in a suspension.

Auxiliary conjunctival provocation tests are utilized, consisting of two solutions for provocation test. The first solution, Conjunctival Provocation Test Grass-Mix LETI 30 HEP/ml, contains Phleum pratense, Lolium perenne, Poa pratensis, Festuca elatior, and Dactylis glomerata pollen extracts for ocular use. The second solution, Conjunctival Provocation Test Olea europaea LETI 30 HEP/ml, contains Olea europaea pollen extract for ocular use.

The primary efficacy endpoint is the mean combined symptom and medication score (cSMS), rated on a scale of 0-6, assessed during the peak of grass and olive pollen pollination following at least 8 injections. This score is collected via a mobile App and incorporates a medication score (ranging from 0 for no medication to 1.5 for intranasal corticoid) and a symptom score (ranging from 0 for none to 3 for severe) evaluating runny nose, sneezing, itchy nose, nasal congestion, itchy eyes, and tearing.

Secondary efficacy parameters include absolute values and changes from baseline during the active pollen season. These assessments involve:

• The mean cSMS throughout the entire pollen season.
• Asthma symptoms and medication scores.
• The severity of allergic rhinoconjunctivitis according to ARIA guidelines and asthma according to GINA guidelines.
• Quality of life measured using RQLQ, pRQLQ, AdolRQLQ, AQLQ, or PAQLQ.
• Scores from ESPIA, VAS, and ACT.
• In participants with asthma, assessments include lung function via FEV1, asthma control through pACT, and the number, severity, and duration of asthma exacerbations.
• Immunological parameters, specifically total and specific IgE and IgG4 to Grass-Mix, Phleum pratense, Phl p1, Phl p5, Olea europaea, and Olee1 measured through ImmunoCAP.
• Total IgA2 levels.