Efficacy of PURETHAL Mites Mixture Subcutaneous Immunotherapy in Adults with Moderate to Severe House Dust Mite-Induced Allergic Rhinitis/Rhinoconjunctivitis
- Trial ID
- 2023-504942-75-01
- Protocol
- PM/0059
- Sponsor
- HAL Allergy B.V.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the clinical efficacy of **PURETHAL Mites Mixture 50,000 AUeq/mL** subcutaneous immunotherapy (SCIT) in adult subjects with moderate to severe allergic rhinitis/rhinoconjunctivitis (ARC) induced by house dust mite (HDM) allergy. This is measured by the difference in the average Total Combined Rhinitis Score (TCRS) during the last 8 weeks of a one-year treatment period, comparing the PM treatment group to the placebo group. Each symptom is individually graded and summed to a maximum of 24 points. The clinical relevance of this objective lies in its potential to provide a therapeutic option for individuals suffering from HDM-induced ARC, which can significantly impact quality of life.
Secondary objectives include:
- Assessing the effect of PM treatment by comparing the average daily Total Nasal Symptom Score (TNSS) and Rhinitis Medication Score (RMS) between PM and placebo during the last 8 weeks of treatment.
- Evaluating the Total Combined Conjunctivitis Score (TCCS) and the change from baseline in the Nasal Provocation Test (NPT) at the end of the study.
- Assessing immunological effects by comparing changes in immunoglobulin levels E, G, and G4 (IgE, IgG, IgG4) against D. pteronyssinus and D. farinae.
- Evaluating the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ(S)) post-treatment.
- Assessing safety and tolerability of PM treatment versus placebo, including treatment-related adverse events, local and systemic reactions, and clinical and laboratory parameters.
- Evaluating the safety of PM treatment on asthma parameters, such as asthma-related concomitant medication, adverse events, and lung function tests.
Participants
The clinical trial involves participants diagnosed with **Moderate to Severe Allergic Rhinitis/Rhinoconjunctivitis** induced by house dust mite allergy, with or without asthma. The study population includes both male and female subjects aged between 18 and 65 years. Participants are required to have a clinical history consistent with moderate to severe house dust mite allergic rhinitis, with or without asthma, for at least one year prior to the first dosing. The trial does not include a vulnerable population. Participants must have a Forced Expiratory Volume 1 (FEV1) greater than 70% at screening and, if asthmatic, their asthma must be controlled throughout the trial. The trial population was selected based on specific criteria, including a positive skin prick test to Dermatophagoides pteronyssinus and/or Dermatophagoides farinae, and an allergen-specific serum IgE level greater than 0.7 U/mL. Lifestyle considerations such as the ability to complete daily electronic diaries under consistent living conditions are also required. The sponsor has not provided information regarding the total number of participants in the study.
Plans and Procedures
The clinical trial is designed as a **randomized, double-blind, placebo-controlled, multi-centre study** to evaluate the efficacy of a subcutaneous immunotherapy preparation in adult subjects with moderate to severe allergic rhinitis/rhinoconjunctivitis, with or without asthma, induced by house dust mite allergy. The trial aims to assess the clinical efficacy of the treatment by measuring the difference in the average Total Combined Rhinitis Score (TCRS) during the last 8 weeks of a one-year treatment period between the active treatment and placebo groups. The trial is expected to commence recruitment on September 1, 2024, and conclude by August 31, 2026.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on specific criteria, such as a clinical history of moderate-severe house dust mite allergic rhinitis, a positive skin prick test, and allergen-specific serum IgE levels. The screening period will also involve daily e-Diary entries to establish baseline symptom scores. Following successful screening, participants will be randomized to receive either the active treatment or placebo. The treatment phase will last for approximately 52 weeks, with regular follow-up visits to monitor safety, tolerability, and efficacy outcomes. The primary endpoint is the average daily TCRS during the last 8 weeks of treatment, while secondary endpoints include changes in nasal provocation test scores, immunoglobulin levels, and quality of life assessments.
The expected length of participant involvement is approximately 60 weeks, including the screening period, treatment phase, and follow-up assessments. Conditions that may lead to early termination from the study include non-compliance with study procedures, adverse events, or withdrawal of consent. Participants will be closely monitored throughout the trial to ensure adherence to the protocol and to address any safety concerns promptly. The study is conducted in accordance with ethical guidelines and regulatory requirements to ensure the safety and well-being of all participants.
Treatment
The clinical trial involves the administration of several experimental and non-experimental treatments. **ALUMINIUM HYDROXIDE** is utilized as a suspension for injection, administered subcutaneously. The maximum daily dose is 0.45 mg, with a total maximum dose of 7.24 mg over a treatment period of up to 52 weeks. This chemical substance is not a pediatric formulation and is used as an auxiliary treatment in the trial.
**PHENOL** is another chemical substance used in the trial, provided as a solution for injection. It is administered subcutaneously with a maximum daily dose of 2.5 mg and a total maximum dose of 40.25 mg over a 52-week period. This formulation is also not intended for pediatric use and serves as an auxiliary treatment.
**SODIUM CHLORIDE** is administered as a solution for injection, with subcutaneous use. The maximum daily dose is 4.5 mg, and the total maximum dose is 72.45 mg over 52 weeks. This chemical substance is used as an auxiliary treatment in the study.
**WATER FOR INJECTION** is provided as a solution for injection, administered subcutaneously. The maximum daily dose is 0.5 ml, with a total maximum dose of 8.05 ml over a 52-week period. This chemical substance is used as an auxiliary treatment.
**LORATADINE** is administered orally in tablet form. The maximum daily dose is 10 mg, with a total maximum dose of 4200 mg over a 60-week period. This chemical substance is used as an auxiliary treatment in the trial.
**AZELASTINE** is provided as eye drops for ocular use. The maximum daily dose is 0.06 mg, with a total maximum dose of 42 mg over a 60-week period. This chemical substance is used as an auxiliary treatment.
**MOMETASONE** is administered as a nasal spray suspension for nasal use. The maximum daily dose is 200 µg, with a total maximum dose of 84 mg over a 60-week period. This chemical substance is used as an auxiliary treatment.
The trial also includes the use of **PURETHAL Mites 50,000 AUeq/mL**, a suspension for injection, administered subcutaneously. The maximum daily dose is 0.5 ml, with a total maximum dose of 8.05 ml over a 52-week period. This subcutaneous immunotherapy preparation is the primary treatment being evaluated for efficacy in the study.
Non-experimental treatments include various **HAL Allergy Prick Tests** and **Provocation Tests**. These are solutions for skin-prick tests and provocation tests, used cutaneously or nasally, with a maximum daily dose of 1 drop or 0.18 ml, respectively, and a total maximum dose of 1 drop or 0.54 ml over a short treatment period of 1 to 3 weeks. These tests are used as comparators or controls in the study.
Efficacy
The efficacy of the clinical trial will be assessed by evaluating the primary and secondary endpoints. The primary endpoint is the average daily Total Combined Rhinitis Score (TCRS) during the last 8 weeks of treatment. This score is a composite measure of symptoms associated with moderate to severe allergic rhinitis/rhinoconjunctivitis induced by house dust mite (HDM) allergy. Each symptom will be individually graded and summed to a maximum of 24 points.
Secondary endpoints include the average daily Total Nasal Symptom Score (TNSS), the average daily Rhinitis Medication Score (RMS), and the average daily Total Combined Conjunctivitis Score (TCCS) during the last 8 weeks of treatment. Additionally, changes from baseline in the Nasal Provocation Test (NPT) using the **Lebel score**, and changes in IgE, IgG, and IgG4 levels against Dermatophagoides pteronyssinus and Dermatophagoides farinae at the end of treatment will be assessed. The Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ(S)) will also be evaluated at the end of treatment.
Safety and tolerability will be monitored throughout the treatment period by assessing treatment-related adverse events, local and systemic reactions. The safety of the treatment on asthma parameters will be evaluated through asthma-related concomitant medication use, asthma-related adverse events, and lung function tests. These assessments will be conducted at specified timepoints, including the end of treatment, to ensure comprehensive evaluation of the treatment's efficacy and safety.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Prior to screening, subjects need to have signed the current approved Informed Consent Form (ICF).
- Male or female subjects age 18-65 years at the time of informed consent.
- 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.
- 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.
- Forced Expiratory Volume 1 (FEV1) > 70% at Screening.
- If a subject is asthmatic, asthma must be controlled during the entire trial. (corresponding to GINA treatment steps 1 or 2). Subjects with seasonal allergy may be included, if they allow to control asthma only with short-acting beta2- agonists and/or dose inhaled corticosteroid (≤400mcg budesonide or equivalent) during TCRS scoring periods.
- 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.
- 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).
- Allergen specific serum IgE level for D. pter and/or D. far of > 0.7 U/mL, assessed at Screening.
- 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.
- Negative serum pregnancy test at screening for women of childbearing potential.
- Females of childbearing potential must be using 2 effective methods of contraception to prevent pregnancy and agree to continue to practice an acceptable method of contraception for the duration of participation in the trial..
Exclusion Criteria
- 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.
- Nasal surgery and/or severe nasal or severe oral disease within 6 months prior to Screening.
- Patients not adhering to the e-Diary procedure and/or procedure for Rescue Medication use during e-Diary phase.
- Moderate and severe asthma (GINA 2022 treatment steps 3 - 5).
- Uncontrolled asthma, as defined by any of the following: a. Asthma Control Test (ACT) ≤19, b. FEV1 ≤70% of predicted value, c. Emergency room visit for asthma attack/exacerbation within 6 months prior to screening, d. At least 1 hospitalization due to asthma within the last year, History of intubation/mechanical ventilation due to asthma, f. More than 2 courses of oral steroids used for treatment of asthma within the last 6 months prior to Screening, g. Daily use of inhaled corticosteroids >400mcg budesonide or equivalent.
- History of anaphylaxis with cardio-respiratory symptoms (food allergy, drugs or an idiopathic reaction).
- 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.
- AIT (subcutaneous, sublingual or oral) with other allergens than HDM within the last 3 months prior to screening or planned during the trial period.
- Participation in a clinical trial within the last 3 months prior to screening (e.g. new investigational drug or biological) or during the trial.
- Any vaccination (including COVID-19) less than 1 week prior to screening, during screening and the up-dosing phase and the TCRS scoring periods.
- 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.
- Severe immune disorders (including autoimmune diseases) and/or diseases requiring immunosuppressive medication.
- Active COVID-19 infection at the time of screening or 2 weeks before.
- Active malignancies or any malignant disease in the last 5 years.
- 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).
- Diseases with a contraindication for the use of adrenaline/epinephrine (e.g. hyperthyroidism, glaucoma).
- Use of prohibited medication and/or not able to discontinue medications that are prohibited during the specified trial periods.
- Moderate to severe nasal obstructive disease such as polyps, septum deviation.
- Clinically significant chronic sinusitis or ocular infection.
- Female subjects of childbearing potential who are pregnant or lactating.
- Alcohol, drug, or medication abuse within the past year and during the trial.
- Any (expected) lack of cooperation or compliance upon the discretion of the investigator.
- Severe psychiatric, psychological, or neurological disorders.
- Employees, 1st degree relatives, or partners of the investigator.
- 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)
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Austria | Not Recruiting | 01 Sept 2024 | 30 |
 Bulgaria | Not Recruiting | 01 Sept 2024 | 83 |
 Germany | Not Recruiting | 01 Sept 2024 | 149 |
 Latvia | Not Recruiting | 01 Sept 2024 | 22 |
 Lithuania | Not Recruiting | 01 Sept 2024 | 22 |
 Poland | Not Recruiting | 01 Sept 2024 | 276 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
HAL Allergy Prick Test Gemeiner Beifuß | Other | PRICK TEST | CUTANEOUS USE | 1 | 1 | PRD630667 |
HAL Allergy Prick Test Positieve Controle 10 mg/ml, oplossing voor huidpriktest | Other | OPLOSSING VOOR HUIDPRIKTEST | CUTANEOUS USE | 1 | 1 | PRD493640 |
HAL Allergy Prick Test Hundeepithelien | Other | PRICK TEST | CUTANEOUS USE | 1 | 1 | PRD630687 |
ALUMINIUM HYDROXIDE | Placebo | — | SUBCUTANEOUS USE | 0.45 | 52 | SUB33625 |
MOMETASONE | Other | — | NASAL USE | 200 | 60 | SUB09045MIG |
PHENOL | Placebo | — | SUBCUTANEOUS USE | 2.5 | 52 | SUB12552MIG |
HAL Allergy Prick Test Gräserpollen-Mischung | Other | PRICK TEST | CUTANEOUS USE | 1 | 1 | PRD648013 |
HAL Allergy Pricktest Negativkontrolle, Pricktestlösung | Other | PRICKTESTLÖSUNG | CUTANEOUS USE | 1 | 1 | PRD6866428 |
WATER FOR INJECTION | Placebo | — | SUBCUTANEOUS USE | 0.5 | 52 | SUB12398MIG |
PRICK TEST Beifuss LETI, 30 HEP/ml Pricktestlösung. | Other | PRICKTESTLÖSUNG | CUTANEOUS USE | 1 | 1 | PRD625124 |