A clinical trial to evaluate the efficacy and safety of a mixture of allergenic extracts of D. pteronyssinus and D. farinae, in patients suffering from allergic rhinoconjunctivitis with or without controlled asthma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

LETI Pharma S.L.U.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Decision date (initial)

2025-10-29

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

The primary objective of the study is to evaluate the clinical efficacy of the SCIT treatments, independently, in comparison with placebo in patients with moderate to severe persistent allergic rhinoconjunctivitis, with or without controlled asthma, after having received 12 administrations of SCIT compared to baseline.

Secondary objectives 20

1. To evaluate clinical efficacy using the cSMS after 6 administrations of SCIT and at 1 and 2 years following the completion of the first study period.
2. To evaluate clinical efficacy based on the progression of rhinitis and conjunctivitis symptoms after 6 and 12 administrations of SCIT, and at 1 and 2 years following the completion of the first study period.
3. o evaluate clinical efficacy based on the progression in the use of rescue medication for rhinoconjunctivitis after 6 and 12 administrations of SCIT, and at 1 and 2 years following the completion of the first study period.
4. To evaluate efficacy in terms of the allergen concentration required to elicit an allergic response after 12 administrations of SCIT, and at 1 and 2 years following the completion of the first study period, using CPT.
5. To evaluate the progression of allergic rhinoconjunctivitis severity after 6 and 12 administrations of SCIT, and at 1 and 2 years following the completion of the first study period, based on the ARIA guidelines.
6. To evaluate the progression of symptoms after 6 and 12 administrations of SCIT, and at 1 and 2 years following the completion of the first study period, using the VAS.
7. To evaluate the immunological response to D. pteronyssinus and D. farinae after 12 administrations of SCIT and at 1 and 2 years following the completion of the first study period (specific IgE, IgG4, and molecular analysis).
8. To evaluate the progression of rhinoconjunctivitis-related quality of life after 6 and 12 administrations of SCIT, and at 1 and 2 years following the completion of the first study period, using the AdolRQLQ and RQLQ questionnaires.
9. To evaluate patient satisfaction with the administered treatments after 12 administrations of SCIT, and at 1 and 2 years following the completion of the first study period, using the ESPIA questionnaire.
10. To evaluate the safety profile during the treatment period in which patients have received 3 years of SCIT."
11. To evaluate the change in rescue medication scores for asthma after 6 and 12 administrations of SCIT, and at 1 and 2 years following the completion of the first study period.
12. To evaluate the change in asthma symptom scores after 6 and 12 administrations of SCIT, and at 1 and 2 years following the completion of the first study period.
13. To evaluate lung function and inflammation after 6 and 12 administrations of SCIT, and at 1 and 2 years following the completion of the first study period, using spirometry and FeNO.
14. To evaluate the progression of asthma-related quality of life after 6 and 12 administrations of SCIT, and at 1 and 2 years following the completion of the first study period, using the pAQLQ and AQLQ questionnaires.
15. To evaluate the progression of asthma control after 6 and 12 administrations of SCIT, and at 1 and 2 years following the completion of the first study period, using the ACT questionnaire.
16. To evaluate the progression of asthma severity after 6 and 12 administrations of SCIT, and at 1 and 2 years following the completion of the first study period, based on the GINA guidelines.
17. To evaluate the progression of asthma exacerbations during the treatment period in which patients have received 12 administrations of SCIT, and at 1 and 2 years following the completion of the first study period.
18. To evaluate the molecular sensitization profile to D. pteronyssinus and D. farinae after 12 administrations of SCIT, and at 1 and 2 years following the completion of the first study period, using the ALEX platform.
19. To evaluate resource use related to the impact on daily life and work/school activities after 6 and 12 administrations of SCIT, and at 1 and 2 years following the completion of the first study period.
20. To evaluate resource use related to the consumption of concomitant medication after 6 and 12 administrations of SCIT, and at 1 and 2 years following the completion of the first study period.

Conditions and MedDRA coding

Allergic rhinoconjunctivitis to Dermatophagoides pteronyssinus and Dermatophagoides farinae

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Patients/legal representatives who have understood and signed the informed consent or assent form.
2. Patients aged ≥ 12 years.
3. Patients with moderate to severe persistent allergic rhinoconjunctivitis (according to the ARIA guidelines¹) for at least one year, with or without controlled asthma, caused by a clinically relevant sensitization to D. pteronyssinus and D. farinae.
4. The presence of allergy must be confirmed according to each of the following diagnostic criteria: Skin prick test ≥ 3 mm to D. pteronyssinus and D. farinae. If a positive skin prick test has been performed within the 12 months prior to inclusion, it will be considered valid for including the patient in the study. Specific IgE level > 0.7 kU/L to D. pteronyssinus and D. farinae. If a blood test within the 12 months prior to inclusion shows specific IgE levels ≥ 0.7 kU/L to D. pteronyssinus and D. farinae, it will be considered valid for inclusion. Specific IgE level > 0.7 kU/L to at least one of the following major allergens: Der p 1, Der p 2, or Der p 23 and Der f 1 or Der f 2. If a blood test within the 12 months prior to inclusion shows specific IgE levels > 0.7 kU/L to Der p 1, Der p 2, or Der p 23 and Der f 1 or Der f 2, it will be considered valid for inclusion. Positive conjunctival provocation test (CPT) with D. pteronyssinus extract. If a CPT (performed with LETI Pharma extracts) has tested positive within the 12 months prior to inclusion, it will be considered valid for inclusion."
5. Patients with a cSMS score ≥ 1.5 points at the time of inclusion.
6. Patients/legal representatives with a mobile phone compatible with the cSMS application and access to the Internet.
7. Asthmatic patients with controlled disease according to GINA guidelines and a FEV₁ ≥ 70% at the time of inclusion.
8. "8. Women of childbearing potential must have a negative urine pregnancy test (childbearing potential is defined as the time from menarche to postmenopause, unless sterilization has occurred by hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) and must be willing to use an effective contraceptive method in accordance with recommendations on contraception and pregnancy testing in clinical trials³, from 14 days prior to the first administration until 4 weeks after the last administration of the investigational product.
9. Patients willing to comply with all study procedures and available for follow-up throughout the duration of the study.
10. Patients/legal representatives have understood and signed the informed consent or assent form.

Exclusion criteria 20

1. Patients previously or currently treated with any type of allergen immunotherapy (AIT) within the last 5 years.
2. Patients sensitized to other mites (Lepidoglyphus destructor and Blomia tropicalis — the latter only in the Canary Islands): if the IgE level is at most 20% of the IgE value for D. pteronyssinus or D. farinae (whichever is lower).
3. Patients sensitized to fungi.
4. Patients sensitized to domestic animal dander who live with or have frequent contact with the animal.
5. Patients sensitized to clinically relevant pollens, as determined by the investigator.
6. Patients with severe or uncontrolled asthma according to GINA 2024 guidelines and a FEV₁ < 70%.
7. Pregnant women, women planning to become pregnant during the study period, or those who are breastfeeding.
8. Any contraindication to allergen immunotherapy (AIT) as defined in the product's Instructions for Use or the Investigator’s Brochure (IB).
9. Patients who required oral corticosteroids within the 12 weeks prior to inclusion.
10. Patients with any contraindication to skin prick testing or conjunctival provocation testing (CPT) with the studied allergens.
11. Patients with chronic urticaria, severe dermographism, severe atopic dermatitis, sunburn, active psoriasis with lesions on the areas where skin tests will be performed, or a history of hereditary angioedema.
12. Any condition or absolute contraindication that prevents the use of adrenaline.
13. Current treatment with any biological or immunosuppressive therapy (except topical immunosuppressants), or treatment received within the last 6 months.
14. Patients with uncontrolled autoimmune diseases, active malignant diseases, or diagnosed immunodeficiency disorders.
15. Patients with lower respiratory tract diseases other than asthma, such as emphysema or bronchiectasis.
16. Patients with any other condition not related to moderate allergic rhinoconjunctivitis or asthma, but of potential severity and that could interfere with treatment and follow-up (e.g., epilepsy, psychomotor impairment, congenital malformations, multiple surgeries, renal diseases, etc.).
17. Patients with known allergy to any component of the vaccine other than the mite allergen extract (active substance).
18. Patients with any medical or psychological condition that, in the investigator’s opinion, could interfere with the patient’s ability to comply with study procedures.
19. Simultaneous participation in another clinical trial.
20. Immediate family members of the investigational team.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The clinical efficacy of both concentrations of SCIT individually, compared to placebo, will be evaluated through the change in the cSMS score from baseline to the timepoint after 12 SCIT doses have been administered. Data collection will be carried out via an electronic diary installed on the patient's mobile device at the time of the first treatment administration.

Secondary endpoints 18

1. Clinical efficacy for rhinoconjunctivitis will be evaluated by the change in the cSMS score from baseline to the timepoint after 6 SCIT administrations, as well as 1 and 2 years after the end of the first study period.
2. Clinical efficacy based on the progression of rhinoconjunctivitis symptoms will be evaluated by the change in the dSS score from baseline to the timepoints after 6 and 12 SCIT administrations, as well as 1 and 2 years after the end of the first study period.
3. Clinical efficacy based on the evolution of medication use for rhinoconjunctivitis will be evaluated by the change in the dMS score from baseline to the timepoints after 6 and 12 SCIT administrations, as well as 1 and 2 years after the end of the first study period.
4. Efficacy in terms of the allergen concentration required to elicit an allergic response will be evaluated by comparing the dose of D. pteronyssinus extract needed to trigger a positive response in the CPT at the start of treatment and after 12 SCIT administrations, as well as 1 and 2 years after the end of the first study period.
5. The severity of allergic rhinoconjunctivitis will be evaluated according to the ARIA guideline classification from baseline to the timepoints after 6 and 12 SCIT administrations, as well as 1 and 2 years after the end of the first study period.
6. The progression of allergic rhinoconjunctivitis symptoms will be evaluated through the change in the patient-reported VAS (Visual Analogue Scale) score from baseline to the timepoints after 6 and 12 SCIT administrations, as well as 1 and 2 years after the end of the first study period. Patients will complete this scale manually, in paper format.
7. The immune response will be evaluated at baseline, after 12 SCIT administrations, and 1 and 2 years after the end of the first study period by assessing changes in the levels of the following immunological parameters: Total and specific IgE against D. pteronyssinus and D. farinae Total and specific IgG4 against D. pteronyssinus and D. farinae Total IgA2.
8. Quality of life related to allergic rhinoconjunctivitis will be evaluated based on the following patient-reported outcomes (PROs): Mean change in the RQLQ questionnaire score from baseline to after 6 and 12 SCIT administrations, as well as 1 and 2 years after the end of the first study period. This PRO will be specifically assessed in adult patients. Patients will complete this questionnaire manually, in paper format.
9. Quality of life related to allergic rhinoconjunctivitis will be evaluated based on the following patient-reported outcome (PRO): Mean change in the AdolRQLQ questionnaire score from baseline to after 6 and 12 SCIT administrations, as well as 1 and 2 years after the end of the first study period. This PRO will be specifically assessed in adolescent patients aged 12 to 17 years.
10. Patient satisfaction will be evaluated using the ESPIA score after 12 SCIT administrations, as well as 1 and 2 years after the end of the first study period. Patients will complete this questionnaire manually, in paper format.
11. The safety profile will be assessed based on the number and percentage of patients who have experienced at least one of the reported events, including the number of episodes/symptoms and the percentage per patient, during the 3-year SCIT treatment period. The severity and causality of each event will also be evaluated.
12. The clinical efficacy based on the evolution of asthma symptoms will be assessed by the change in the dSSa score from baseline to after the 6th and 12th SCIT administrations, as well as 1 and 2 years after the end of the first study period.
13. The clinical efficacy based on the evolution of medication use will be assessed by the change in the dMSa score from baseline to after the 6th and 12th SCIT administrations, as well as 1 and 2 years after the end of the first study period.
14. Pulmonary function will be assessed based on the mean change in FEV1 using spirometry, while pulmonary inflammation will be assessed based on the mean change in FeNO from baseline to after the 6th and 12th SCIT administrations, as well as 1 and 2 years after the end of the first study period.
15. 14. Asthma-related quality of life will be assessed in adult patients based on the mean change in AQLQ score, and in patients aged 12 to 17 years based on the mean change in pAQLQ score, from baseline to after the 6th and 12th SCIT administrations, as well as 1 and 2 years after the end of the first study period.
16. Asthma control will be assessed in all patients based on the mean change in ACT score from baseline to after the 6th and 12th SCIT administrations, as well as 1 and 2 years after the end of the first study period. Patients will complete these questionnaires manually, in paper format.
17. The evolution of asthma severity will be assessed based on the change in asthma classification according to the GINA guidelines from baseline to after the 6th and 12th SCIT administrations, as well as 1 and 2 years after the end of the first study period.
18. The evolution of exacerbations will be assessed at each treatment administration based on the number, severity, and duration of exacerbations experienced by the patients from baseline to after the 12th SCIT administration, as well as 1 and 2 years after the end of the first study period.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Auxiliary 13

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

LETI Pharma S.L.U.

Sponsor organisation

LETI Pharma S.L.U.

Address

Calle Del Sol 5, Zona Industrial Tres Cantos Zona Industrial Tres Cantos

City

Tres Cantos

Postcode

28760

Country

Spain

Scientific contact point

Organisation

LETI Pharma S.L.U.

Contact name

Mónica Ruiz

Public contact point

Organisation

LETI Pharma S.L.U.

Contact name

Mónica Ruiz

Third parties 2

Locations

1 EU/EEA country · 41 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 18 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications