E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
House Dust Mite-Induced Rhinoconjunctivitis |
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E.1.1.1 | Medical condition in easily understood language |
Rhinoconjunctivitis caused by allergy to house dust mites |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10034382 |
E.1.2 | Term | Perennial allergic rhinitis |
E.1.2 | System Organ Class | 100000004855 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of HDM-SPIRE in the reduction of symptoms and the use of allergy rescue medication associated with HDM allergy in subjects with clinically relevant symptoms. |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the safety and tolerability of HDM-SPIRE
- To evaluate the effect of HDM-SPIRE on rhinoconjunctivitis specific quality of life
- To evaluate the effect of HDM-SPIRE on sleep quality |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female, aged 18-65 years.
- A reliable history consistent with moderate to severe rhinoconjunctivitis (sneezing, rhinorrhoea, itchy nose, nasal blockage and/or itchy eyes, red eyes, watering eyes and/or itchy ear/palate) on exposure to HDM for at least 1 year and which has required symptomatic treatment on at least one occasion during the last year.
- Mean TRSS ≥10 from 4 nasal and 4 non-nasal symptoms over a consecutive 7 day period before the Screening Visit 1B/C.
- Der p and Der f specific IgE each ≥0.7 kU/L measured by ImmunoCAP®.
- Positive skin prick test (preferably using the ALK-Abello Allergen Extract test) to Der p and Der f with a wheal diameter at least 5 mm (average of longest and orthogonal) larger than that produced by the negative control.
- Provide written informed consent.
Additional Inclusion Criteria at End of BAE
- Mean TRSS ≥12 from 4 nasal and 4 non-nasal symptoms during the BAE period (3-week period before randomisation).
- Completed the eDiary during the BAE on at least 16 days (>75% of occasions). |
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E.4 | Principal exclusion criteria |
- Diagnosis of asthma requiring GINA Step 3 or higher treatment.
- If asthmatic, experienced a deterioration of asthma that resulted in emergency treatment or hospitalisation in the 12 months before randomisation, or experienced a lifethreatening asthma attack (e.g. one requiring intubation and mechanical ventilation) at any time in the past.
- Used any oral or parenteral corticosteroids at any time within 1 month prior to Screening Visit 1B/C.
- Asthma requiring high-dose inhaled corticosteroids (ICS) or anti-IgE therapy within 6 months prior to Screening Visit 1B/C.
- Forced expiratory volume in 1 second (FEV1) <80% of predicted, or other evidence of partly controlled or uncontrolled asthma.
- Clinically significant confounding symptoms of allergy to relevant local seasonal allergens (e.g. ragweed, mugwort, tree, grass or mould) and cannot complete the BAE and the final PAC period at 50-52 weeks (PAC3) outside the respective allergy seasons.
- IgE >0.7 kU/l to other perennial allergens (e.g. animal dander, cockroach, mould) which cannot be avoided during the study or where sampling for these allergens demonstrates significant levels within the subject’s home from dust and/or vacuum cleaner samples, analysed using Indoor Biotechnologies Allergen Analysis Service.
- Intends to be away for 7 days or more during the final PAC period at 50-52 weeks (PAC3), or whose lifestyle means that there is a high likelihood of them
being away from home for more than 7 days during the PAC3 period.
- Received an immunosuppressive treatment within 3 months prior to screening (except steroids for allergic and asthma symptoms).
- Previous immunotherapy treatment with any HDM allergen for more than 1 month within 5 years prior to screening.
- History of significant recurrent acute sinusitis, defined as 2 episodes per year for the last 2 years, all of which required antibiotic treatment, or a history of chronic sinusitis, defined as sinus symptoms lasting greater than 12 weeks that include 2 or more major factors or 1
major factor and 2 minor factors. Major factors are defined as facial pain or pressure, nasal obstruction or blockage, nasal discharge or purulence or discoloured postnasal discharge, purulence in nasal cavity, or impaired or loss of smell. Minor factors are defined as headache, fever, halitosis, fatigue, dental pain, cough, and ear pain, pressure, or fullness.
Additional Exclusion Criteria at end of BAE
- Used any oral or parenteral corticosteroid during the BAE period. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Mean Combined Score (CS) during the PAC3 period in the HDM-SPIRE treatment groups compared with the mean CS in the placebo group. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Weeks 50 to 52 after randomisation |
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E.5.2 | Secondary end point(s) |
- Clinical Global Impression of Change in Rhinoconjunctivitis Symptoms for the HDM-SPIRE treatment groups compared with placebo at the end of study.
- Mean TRSS in the HDM-SPIRE treatment groups compared with placebo during the PAC3 period.
- Mean component scores of the TRSS (nasal and non-nasal) in the HDM-SPIRE treatment groups compared with placebo during the PAC3 period.
- Mean RMS in the HDM-SPIRE treatment groups compared with placebo during the PAC3 period.
- Mean Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score in the HDM-SPIRE treatment groups compared with placebo at the end of the PAC3 period.
- Number of days subjects in the HDM-SPIRE treatment groups have no moderate or severe RSS symptoms without rescue medication usage compared with placebo during the PAC3 period. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Weeks 50 to 52 after randomisation |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 32 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
France |
Germany |
Italy |
Netherlands |
Spain |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The end of the study is when the last subject completes the Period 3 Follow-Up (Visit 5) |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 15 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 15 |