Evaluation of Biological Activity of Allergenic Mite Extracts (Dermatophagoides pteronyssinus, Dermatophagoides farinae, Blomia tropicalis, Lepidoglyphus destructor) in Sensitized Patients

The primary objective of this study is to evaluate **in vivo** the concentration of allergenic extracts of mites, specifically **Dermatophagoides pteronyssinus**, **Dermatophagoides farinae**, **Blomia tropicalis**, and **Lepidoglyphus destructor**, that induce a papule size equivalent to that produced by a 10 mg/ml solution of **histamine dihydrochloride**. This evaluation aims to standardize mite allergenic extracts in biological units, which is clinically relevant for ensuring accurate diagnosis and treatment of **allergies**.

Secondary objectives include:

• Determining the **in vitro** biological potency of mite extract concentrations that produce a wheal size equivalent to a 10 mg/ml histamine dihydrochloride solution, ensuring consistency and reproducibility.
• Evaluating the tolerability and safety of the drugs under study.

The clinical trial involves participants diagnosed with **allergies**, specifically those sensitized to allergens such as Dermatophagoides pteronyssinus, Dermatophagoides farinae, Blomia tropicalis, and Lepidoglyphus destructor. The study population includes both male and female subjects, aged between 18 and 65 years, who are in general good health and have a documented medical history supporting their allergy diagnosis. Participants were selected based on their demonstrated sensitization to the specified allergens, confirmed through a skin prick test or specific IgE serum levels. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Lifestyle factors such as diet and physical activity are not specified as considerations for this study.

The clinical trial is designed to evaluate the **in vivo** concentration of allergenic extracts of mites, specifically **Dermatophagoides pteronyssinus**, **Dermatophagoides farinae**, **Blomia tropicalis**, and **Lepidoglyphus destructor**, that cause a papule size equivalent to that produced by a solution of **histamine dihydrochloride** at 10 mg/ml. This is a Phase IV, randomized, double-blind, controlled trial aimed at standardizing mite allergenic extracts in biological units. The trial is expected to commence on September 1, 2024, and conclude by November 30, 2024.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (18-65 years), informed consent, and a history of allergy with demonstrated sensitization to specific allergens. The primary endpoint is the area of the wheal (mm²) that occurs at the cutaneous level after administration of the extracts in the skin-prick test. Secondary endpoints include determining the **in vitro** biological potency expressed as HEP and assessing safety through adverse reaction analysis.

The trial involves a single treatment period with a maximum daily dose of 10 mg/ml for each allergenic extract. Participants will be involved for the duration of the trial, with conditions for early termination including withdrawal of consent or adverse reactions. Follow-up visits will monitor the response to the allergenic extracts and ensure participant safety. The end-of-study visit will conclude the participant's involvement, with a final assessment of the trial's objectives and endpoints.

The clinical trial involves the use of several **experimental medications** in the form of solutions for skin-prick tests. The first experimental medication is the **Histamine dihydrochloride skin-prick test**. This solution is used as a reference standard to evaluate the biological activity of allergenic extracts. The pharmaceutical form is a solution specifically designed for skin-prick testing. The active substance, **histamine dihydrochloride**, is of chemical origin. The solution is administered via subcutaneous use, with a maximum daily dose and total dose of 10 mg/ml. The treatment period is limited to one day.

Another experimental medication used in the trial is the **Lepidoglyphus destructor skin-prick test**. This solution contains an allergenic extract of **Lepidoglyphus destructor**, a structurally diverse substance. The pharmaceutical form is a solution for skin-prick testing, administered subcutaneously. The maximum daily and total dose is 10 mg/ml, with a treatment period of one day.

The **Dermatophagoides pteronyssinus skin-prick test** is also utilized in the study. This solution contains an allergenic extract of **Dermatophagoides pteronyssinus**, classified as a structurally diverse substance. It is administered subcutaneously, with a maximum daily and total dose of 10 mg/ml, and a treatment period of one day.

Additionally, the trial includes the **Blomia tropicalis skin-prick test**. This solution comprises an allergenic extract of **Blomia tropicalis**, another structurally diverse substance. The administration route is subcutaneous, with a maximum daily and total dose of 10 mg/ml, and a treatment period of one day.

The final experimental medication is the **Dermatophagoides farinae skin-prick test**. This solution contains an allergenic extract of **Dermatophagoides farinae**, also a structurally diverse substance. It is administered subcutaneously, with a maximum daily and total dose of 10 mg/ml, and a treatment period of one day.

All experimental medications are manufactured by DIATER LABORATORIO DE DIAGNOSTICO Y APLICACIONES TERAPEUTICAS S.A. and are not pediatric formulations. The trial does not involve any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatment. Participant compliance is monitored through the administration of the skin-prick tests, ensuring adherence to the dosing schedule and treatment period.

The efficacy of the clinical trial will be assessed by evaluating the concentration of allergenic extracts of mites that cause a papule of a size equivalent to that produced by a solution of **histamine dihydrochloride** at 10 mg/ml. The primary endpoint is the area of the wheal (mm²) that occurs at the cutaneous level after the administration of the extracts in the skin-prick test. This will be used for the calculation of the primary endpoint. The secondary endpoints include determining the in vitro biological potency expressed as Histamine Equivalent Units (HEP), where 1 HEP equals 10,000 biological units, of the concentration of the investigational product that elicits a wheal of a size equivalent to that produced by the histamine solution. Additionally, safety will be assessed through a descriptive analysis of adverse reactions that may occur during the course of the study.