A Randomized, Double-Blind, Placebo-Controlled, Multi-Centre Study to Assess the Efficacy of PURETHAL Mites Mixture 50,000 AUeq/mL Subcutaneous Immunotherapy in Adult Subjects With Moderate to Severe Allergic Rhinitis/Rhinoconjunctivitis With or Without Asthma Induced by House Dust Mite (HDM)

NCT ID: NCT06920771

Last Updated: 2025-04-10

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 552 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-09-09
• Study Completion Date: 2026-08-31

Brief Summary

Rationale: Allergic rhinitis/rhinoconjunctivitis (ARC) is a global health problem, affecting 10-25% of the population. Allergen-specific immunotherapy is the only disease-modifying therapeutic option for subjects with house dust mites (HDM)-induced allergic rhinitis/rhinoconjunctivitis. This Phase 3 clinical study aims to demonstrate the effecacy of PURETHAL Mites (PM) Mixture subcutaneous immunotherapy (SCIT) compared to a placebo over one year of treatment in patients with moderate to severe HDM- induced allergic rhinitis/rhinoconjunctivitis (ARC), while also prioritizing the safety of the treatment. PM Mixture is a suspension of chemically modified extract from the house dust mites Dermatophagoides pteronyssinus (D. pter) and Dermatophagoides farinae (D. far), adsorbed to aluminium hydroxide. Modified extracts (allergoids) are associated with reduced allergenicity but with preserved immunogenicity. Based on the previous studies the dose of 0.5 mL of PM Mixture solution with concentration 50,000 AUeq/mL (allergen units in millilitre) was selected for this Phase 3 clinical study.

Objectives: The primary objective is to assess the efficacy of PM Mixture 50,000 AUeq/mL (0.5 mL) SCIT based on an average Total Combined Rhinitis Score (TCRS), which will be compared between PM Mixture and placebo groups. The TCRS consists of rhinitis symptom score and medication score measured daily over the last 8 weeks of the 1 year treatment.

Other secondary efficacy parameters will be compared between treatment groups to show efficacy: rhinitis symptom and medication scores separately as well as a combined symptom and medication score for nasal symptoms only (CSMS(n)); Total Combined Conductivities Score; nasal provocation test; immunological blood markers such as immunoglobulins E, G and G4; and Rhinitis Quality of Life Questionnaire (standardised) (RQLQ(S)).

Trial design: This is a randomized, double-blind, placebo controlled multi-centre clinical trial where subjects are participating for about 14 months.

Trial population: Patients (18-65 years of age) suffering from moderate to severe ARC induced by HDM with or without controlled asthma can be included in the study. The main criteria to evaluate the HDM allergy will be done by the following parameters: allergic medical history to HDM minimum 1 year; positive skin prick test and nasal provocation test HDM D. pter and/or D. far; certain level of allergen-specific immunoglobulin E to D. pter or D. far, and most importantly they should have sufficient rhinitis symptom score measured during 2 weeks at screening. Additionally patients should have sufficient lung functions confirmed by the spirometry, they may have asthma which should be controlled. Patients with a chronic or acute disease that might place the subject at an additional risk will not be included. Certain medications which can interfere with the study treatment or increase the health risks should be washed-out and can not be taken during the study.

Approximately 920 HDM-allergic subjects will be screened in order after the screening period to enroll 552 subjects.

Conditions

House Dust Mite Allergy; House Dust Mite Rhinitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo Comparator: placebo

Increasing volumes of placebo, will be administered by subcutaneous injection (starting with 0.05 ml) at weekly intervals till the maintenance dose (0.5 ml) is reached. Subsequently, maintenance dosages, corresponding to 0.5 ml of placebo, are given at 4-weekly intervals.

Group Type: PLACEBO_COMPARATOR

PURETHAL Mites 50,000 AUeq/ml

Intervention Type: BIOLOGICAL

Biological/Vaccine: Placebo

Increasing volumes of placebo, will be administered by subcutaneous injection (starting with 0.05 ml) at weekly intervals till the maintenance dose (0.5 ml) is reached. Subsequently, maintenance dosages, corresponding to 0.5 ml of placebo, are given at 4-weekly intervals

Biological/Vaccine: Placebo

Intervention Type: BIOLOGICAL

Increasing dosages, corresponding to increasing volumes of drug solution (starting with 0.05 ml), will be administered by subcutaneous injection at weekly intervals till the maintenance dose (0.5 ml) is reached. Subsequently, maintenance dosages, corresponding to 0.5 ml of drug solution, are given at 4-weekly intervals.

Experimental: PURETHAL Mites, 50,000 AU/ml

Increasing dosages, corresponding to increasing volumes of drug solution (starting with 0.05 ml), will be administered by subcutaneous injection at weekly intervals till the maintenance dose (0.5 ml) is reached. Subsequently, maintenance dosages, corresponding to 0.5 ml of drug solution, are given at 4-weekly intervals.

Group Type: ACTIVE_COMPARATOR

PURETHAL Mites 50,000 AUeq/ml

Intervention Type: BIOLOGICAL

Biological/Vaccine: Placebo

Increasing volumes of placebo, will be administered by subcutaneous injection (starting with 0.05 ml) at weekly intervals till the maintenance dose (0.5 ml) is reached. Subsequently, maintenance dosages, corresponding to 0.5 ml of placebo, are given at 4-weekly intervals

Biological/Vaccine: Placebo

Intervention Type: BIOLOGICAL

Increasing dosages, corresponding to increasing volumes of drug solution (starting with 0.05 ml), will be administered by subcutaneous injection at weekly intervals till the maintenance dose (0.5 ml) is reached. Subsequently, maintenance dosages, corresponding to 0.5 ml of drug solution, are given at 4-weekly intervals.

Interventions

PURETHAL Mites 50,000 AUeq/ml

Biological/Vaccine: Placebo

Increasing volumes of placebo, will be administered by subcutaneous injection (starting with 0.05 ml) at weekly intervals till the maintenance dose (0.5 ml) is reached. Subsequently, maintenance dosages, corresponding to 0.5 ml of placebo, are given at 4-weekly intervals

Intervention Type: BIOLOGICAL

Biological/Vaccine: Placebo

Increasing dosages, corresponding to increasing volumes of drug solution (starting with 0.05 ml), will be administered by subcutaneous injection at weekly intervals till the maintenance dose (0.5 ml) is reached. Subsequently, maintenance dosages, corresponding to 0.5 ml of drug solution, are given at 4-weekly intervals.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. Prior to screening, subjects need to have signed the current approved Informed Consent Form (ICF).

2. Male or female subjects age 18-65 years at the time of informed consent.

3. Clinical history consistent with moderate-severe HDM allergic rhinitis (with or without asthma) according to the ARIA classification (Allergic Rhinitis and its Impact on Asthma) (Bousquet et al., 2008), for at least one year prior to the first dosing.

4. Subjects should be able and willing to complete daily e-Diaries for a period of 4 weeks during the screening period, 1 week after maintenance visit 7, and for a period of 8 weeks at the end of treatment under the same living conditions.

5. Forced Expiratory Volume 1 (FEV1) > 70% at Screening.

6. If a subject is asthmatic, asthma must be clinically controlled for at least three months before the screening using inhaled steroids and / or Long Acting Beta Agonists (corresponding to GINA treatment steps 1 -3) and inhaled steroid use should be on a stable, not higher dose than of ≤400 µg budesonide per day or dose-equivalent (≤500 µg beclometasone dipropionate; ≤160 µg ciclesonide;

≤250 µg fluticasone propionate; ≤200 µg mometasone furoate). Patients with asthma should use their standard asthma medication throughout the whole study period to ensure their asthma remains controlled.

7. Positive SPT to D. pter and/or D. far (mean wheal diameter ≥ 3 mm, negative control should be < 2 mm, histamine positive control should be ≥ 3 mm), assessed at Screening.

8. Subjects with a positive NPT for D. pter extract at Screening (Lebel score ≥6 at 10,000 AU/mL, test should be postponed, if baseline score is ≥ 3 or if negative control score is > 3).

9. Allergen specific serum IgE level for D. pter and/or D. far of > 0.7 U/mL, assessed at Screening.

10. Subjects need to have an average daily TNSS of at least 8 out of 12 points at baseline, determined according to the daily e-Diary entries during 2 weeks of baseline assessment. Subjects should have a minimum e-Diary entry compliance of 70% for which the average is calculated.

11. Negative serum pregnancy test at screening for women of childbearing potential.

12. Females of childbearing potential must be using highly effective and acceptable methods of birth control (as per the CTFG recommendations) to prevent pregnancy and agree to continue to practice an acceptable method of contraception for the duration of participation in the trial. Contraceptive measures considered adequate are:

1. combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal)

2. progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)

3. intrauterine device (IUD)

4. intrauterine hormone-releasing system (IUS)

5. bilateral tubal occlusion

6. vasectomised partner

Exclusion Criteria

1. A clinically relevant history of symptomatic seasonal ARC and/or a positive SPT (mean wheal diameter ≥ 3 mm) caused by an allergen (including animal hair and dander), to which the subject is regularly exposed and/or exposure is overlapping with the e-Diary completion periods at Screening and at the end of treatment.

2. Nasal surgery and/or severe nasal or severe oral disease within 6 months prior to Screening.

3. Patients not adhering to the e-Diary procedure and/or procedure for Rescue Medication use during e-Diary phase.

4. Severe asthma (GINA 2022 treatment steps 4 - 5).

5. Uncontrolled asthma, as defined by any of the following:

1. Asthma Control Test (ACT) ≤19,

2. FEV1 ≤70% of predicted value,

3. Emergency room visit for asthma attack/exacerbation within 6 months prior to screening,

4. At least 1 hospitalization due to asthma within the last year,

5. History of intubation/mechanical ventilation due to asthma,

6. More than 2 courses of oral steroids used for treatment of asthma within the last 6 months prior to Screening,

7. Daily use of inhaled corticosteroids >400mcg budesonide or equivalent.

6. History of anaphylaxis with cardio-respiratory symptoms (food allergy, drugs or an idiopathic reaction).

7. Previous treatment with AIT with HDM allergen or a cross-reacting allergen for more than 1 month at the maintenance level within the last 5 years. Initiation of HDM SCIT is acceptable, if treatment has been discontinued before reaching maintenance dose.

8. AIT (subcutaneous, sublingual or oral) with other allergens than HDM within the last 3 months prior to screening or planned during the trial period.

9. Participation in a clinical trial within the last 3 months prior to screening (e.g.

new investigational drug or biological) or during the trial. 10. Any vaccination (including COVID-19) less than 1 week prior to screening, during screening and the up-dosing phase and the TCRS scoring periods. 11. Any immunosuppressive treatment or anti-IgE therapy within the last 6 months prior to the first dosing of the trial drug and during the trial 12. Any treatment with β-adrenergic blockers unless prescribed as per treatment standards to the subject if the medical benefit will prevail the risks upon investigators discretion. 13. Hypersensitivity to any of the other components of the investigational product. 14. Severe immune disorders (including autoimmune diseases) and/or diseases requiring immunosuppressive medication. 15. Active COVID-19 infection at the time of screening or 2 weeks before. 16. Active malignancies or any malignant disease in the last 5 years. 17. A chronic or acute disease that in the opinion of the investigator might place the subject at an additional risk, including but not limited to the following: cardiovascular insufficiency, any severe or unstable lung diseases, endocrine disorders, clinically significant renal or hepatic diseases, haematological disorders, severe atopic dermatitis, other relevant skin diseases (affecting SPT testing areas). 18. Diseases with a contraindication for the use of adrenaline/epinephrine (e.g.

hyperthyroidism, glaucoma). 19. Use of prohibited medication and/or not able to discontinue medications that are prohibited during the specified trial periods. 20. Moderate to severe nasal obstructive disease such as polyps, septum deviation. 21. Clinically significant chronic sinusitis or ocular infection. 22. Female subjects of childbearing potential who are pregnant or lactating. 23. Alcohol, drug, or medication abuse within the past year and during the trial.

24. Any (expected) lack of cooperation or compliance upon the discretion of the investigator. 25. Severe psychiatric, psychological, or neurological disorders. 26. Employees of the Sponsor, CRO, clinical study site and/or who are 1st grade relatives, or partners of the investigator. 27. Known commitment to an institution by virtue of an order issued either by the judicial or the administrative authorities 28. Expected changes in average HDM exposure during the trial (e.g. new avoidance measures, relocation and holidays or trips lasting more than 10 days during the efficacy assessment period)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ergomed

INDUSTRY

Sponsor Role: collaborator

ClinCompetence Cologne GmbH

UNKNOWN

Sponsor Role: collaborator

HAL Allergy

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hans Hoogeveen

Role: STUDY_DIRECTOR

Head of Clinical Development

Locations

UMBAL Kaspela

Plovdiv, , Bulgaria

Medical Center Prolet EOOD

Rousse, , Bulgaria

Medical Center Smolyan

Smolyan, , Bulgaria

DCC Convex

Sofia, , Bulgaria

Diagnostic-Consulativ Senter Ascendent

Sofia, , Bulgaria

University Hospital Alexandrovska

Sofia, , Bulgaria

Emovis GmbH

Berlin, , Germany

Praxis Dr. Ginko

Bonn, , Germany

Praxis Dr. Elke Decot

Dreieich, , Germany

HNO-Praxis Dr. Udo Schäfer

Dresden, , Germany

HNO Praxis Dr. Uta Thieme

Duisburg, , Germany

Medizentrum Essen-Borbeck

Essen, , Germany

Pneumologisches Forschungsinstitut Hohegeest GbR

Geesthacht, , Germany

HNO-Facharztpraxis Alte Post

Göttingen, , Germany

HNO Research GmbH

Itzehoe, , Germany

Hospital Schleswig-Holstein. Klinik für Dermatologie, Venerologie und Allergologie.

Kiel, , Germany

BAG Prof. G. Hoheisel/Dr. A. Bonitz Praxis für Pneumologie und Allergologie - Studienzentrum

Leipzig, , Germany

Praxis Dr. Bohn

Mittweida, , Germany

Ballenberger, Freytag, Wenisch -Institut für klinische Forschung GmbH

Neu-Isenburg, , Germany

Studienzentrum MOL BAG Dres. E.Hippke & S. Runge

Neuenhagen, , Germany

KliFOs - Klinische Forschung Osnabrück

Osnabrück, , Germany

Studienzentrum Dr.Schlenska

Peine, , Germany

Studienzentrum Dr.Laßmann

Saalfeld, , Germany

Allergo GmbH - Prüfzentrum Schorndorf

Schorndorf, , Germany

Klinikum Stuttgart - Krankenhaus Bad Cannstatt

Stuttgart, , Germany

LOR Clinic

Riga, , Latvia

The Center of Investigation in Treatment of Allergyc Diseases

Riga, , Latvia

CD8 clinic

Kaunas, , Lithuania

Lithuanian University of Health Sciences Kauno klinikos

Kaunas, , Lithuania

Inovatyvios alergologijos centras

Vilnius, , Lithuania

JSC Center for Diagnosis and Treatment of Allergic Diseases

Vilnius, , Lithuania

JSC Family Doctor

Vilnius, , Lithuania

JSC Inlita

Vilnius, , Lithuania

JSC Verkiu clinic

Vilnius, , Lithuania

NZOZ Homeo Medicus Poradnia Alergologiczna

Bialystok, , Poland

Prywatna Praktyka Lekarska Gabinet Pediatryczno-Alergologiczny Anna Płoszczuk

Bialystok, , Poland

Specjalistyczna Praktyka Lekarska AlerMedica

Bialystok, , Poland

Centrum Medyczne KERmed

Bydgoszcz, , Poland

Pratia - Ośrodek Badań Klinicznych

Częstochowa, , Poland

Clinica Vitae Spółka z o. o.

Gdansk, , Poland

Indywidualna Specjalistyczna Praktyka Lekarska Elżbieta Matusz

Gryfice, , Poland

Centrum Medyczne Angelius Provita

Katowice, , Poland

Specjalistyczna Praktyka Lekarska dr n.med. Joanna Orlicz-Widawska

Katowice, , Poland

PZU Zdrowie Centra Medyczne Kielce

Kielce, , Poland

Indywidualna Specjalistyczna Praktyka Lekarska Jan Zdanowski Specjalista Alergolog

Koszalin, , Poland

Centrum Nowoczesnych Terapii "Dobry Lekarz" Sp. z o.o.

Krakow, , Poland

Krakowskie Centrum Medyczne Sp. z o.o - FutureMeds Kraków

Krakow, , Poland

Małopolskie Centrum Alergologii sp z o.o.

Krakow, , Poland

Clinmedica Research sp. z o.o.

Lodz, , Poland

CM Szpital Św. Rodziny

Lodz, , Poland

IP Clinic Sp. z o. o.

Lodz, , Poland

Medical University of Lodz

Lodz, , Poland

Centrum Diagnostyczno-Terapeutyczne Medicus Sp. z o.o.

Lubin, , Poland

ALERGOTEST s.c. Specjalistyczne Centrum Medyczne

Lublin, , Poland

Centrum Alergoologii Specjalistyczna Przychodnia Alergologiczna

Lublin, , Poland

Pro Life Medica Sp. z o.o.

Lublin, , Poland

Uniwersytecki Szpital Kliniczny Nr 4 w Lublinie

Lublin, , Poland

Centrum Alergologii

Poznan, , Poland

NZOZ Alergo-Med

Poznan, , Poland

Poradnie Specjalistyczne Alergologia Plus - Justyna Rakowicz

Poznan, , Poland

NSZOZ Puls Med

Skarżysko-Kamienna, , Poland

Alergo-Med Specjalistyczna Przychodnia Lekarska Sp. z o. o.

Tarnów, , Poland

Gabinet Lekarski Bożena Kubicka-Kozik

Tomaszów Mazowiecki, , Poland

Centrum Alergologii Irmed Irena Wojciechowska

Warsaw, , Poland

ETG Warszawa

Warsaw, , Poland

POLIMEDICA CENTRUM BADAŃ, PROFILAKTYKI I LECZENIA Sp. z o.o. - POLIMEDICA PTG

Warsaw, , Poland

All-Med - Specjalistyczna Opieka Medyczna - Medyczny Instytut Badawczy

Wroclaw, , Poland

NZOZ Centrum Usług Medycznych "PROXIMUM" Sp. z o. o.

Wroclaw, , Poland

Countries

Bulgaria; Germany; Latvia; Lithuania; Poland

Other Identifiers

2023-504942-75-01

Identifier Type: CTIS

Identifier Source: secondary_id

PM/0059

Identifier Type: -

Identifier Source: org_study_id