E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
moderate to severe allergic rhinitis or rhinoconjunctivitis with or without asthma |
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E.1.1.1 | Medical condition in easily understood language |
moderate to severe allergic cold with or without asthma |
umiarkowany do ciężkiego alergiczny katar ze współistniejącą astmą lub bez astmy |
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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 | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001723 |
E.1.2 | Term | Allergic rhinitis |
E.1.2 | System Organ Class | 100000004855 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001728 |
E.1.2 | Term | Allergic rhinoconjunctivitis |
E.1.2 | System Organ Class | 100000004853 |
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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 safety and tolerability of an accelerated high dose escalation scheme with one strength for allergen immunotherapy with NHD D.p./D.f. 50%/50% compared to the standard escalation scheme involving 3 strengths in adults and adolescents with rhinitis or rhinoconjunctivitis caused by house dust mite allergens with or without allergic asthma |
ocena bezpieczeństwa i tolerancji przyspieszonego schematu zwiększania z wysoką dawką i jednym stężeniem preparatu w immunoterapii alergenowej z zastosowaniem NHD D.p./D.f. 50%/50% w porównaniu ze standardowym schematem zwiększania dawki obejmującym 3 stężenia preparatu u osób dorosłych i młodzieży z nieżytem nosa lub nieżytem nosa i spojówek wywołanymi przez alergeny roztoczy kurzu domowego z lub bez współwystępowania astmy alergicznej. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Written informed consent given from patient (and parents/legal guardian(s), as applicable)
2. Age between 12 and ≤ 65 years
3. IgE-mediated moderate to severe allergic rhinitis or rhinoconjunctivitis with or without allergic asthma caused by house dust mite allergens (established and documented as part of the screening procedures)
4. Symptoms of allergic rhinitis or rhinoconjunctivitis triggered by house dust mite exposure over at least the last 2 years
5. No diagnosis of bronchial asthma in medical history, or confirmed diagnosis of asthma as being “well controlled”
6. Previous symptomatic anti-allergic treatment for at least 2 years prior to enrolment
7. Negative SARS-CoV-2 test result |
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E.4 | Principal exclusion criteria |
General criteria: 1. Patients and if relevant parents/legal guardian(s) are unable to understand and comply with the requirements of the trial, as judged by the investigator 2. Currently participating in another clinical trial or participating in any other clinical trial within 30 days prior informed consent for this trial 3. Low adherence to trial procedures expected or inability to understand instructions/trial documents by participant and/or parents/legal guardian(s) 4. Involvement in the planning and conduct of the trial 5. Patients and if relevant parent/legal guardian is employee of Allergopharma GmbH & Co. KG or of one of the trial sites or CRO 6. Any relationship of dependence with the sponsor or with the investigator 7. Previous randomization to treatment in the present trial 8. Mentally disabled 9. Institutionalized due to an official or judicial order
For female patients with childbearing potential 10. Positive urine pregnancy test or pregnant 11. Wish to become pregnant during the course of the trial 12.Not using highly effective and reliable contraception, as judged by the investigator (reliable and highly effective methods of birth control defined as failure rate less than 1% per year) 13. Wish to breast feed or breast feeding
Immunotherapy criteria: 14. History of a confirmed anaphylaxis after an AIT injection 15. AIT with house dust mite allergoids or allergens within the last 5 years 16. Current treatment with any kind of allergen immunotherapy (AIT) 17. AIT with unknown allergen within the last 5 years Diseases and health status: 18. Clinically relevant chronic rhinoconjunctival or respiratory symptoms related to other reasons than allergy 19. Forced expiratory volume in 1 second (FEV1) < 70 % of predicted normal values according to Quanjer (Quanjer et al. 2012) under adequate asthma treatment according to GINA recommendation (GINA 2020) 20. Uncontrolled or partly controlled asthma according to GINA recommendation (INA 2020) 21. Acute asthma attack within the last 6 months prior to randomization defined as unscheduled doctors visit, hospitalization, or emergency visit 22. Severe acute or chronic diseases (e.g. COVID-19, chronic urticaria, mastocytose, active tuberculosis, diabetes mellitus type I, malignant neoplasia, chronic renal failure), severe inflammatory diseases (liver, kidneys), acute viral and bacterial infections presenting with fever 23. Autoimmune diseases, immune defects including immunosuppression, immune-complexinduced immunopathies (e.g. HIV, post-transplant patients, lupus erythematodes [SLE], vitiligo, Grave’s disease, multiple sclerosis) 24. Severe psychiatric and psychological disorders including impairment of cooperation (e.g. alcohol or drug abuse) 25. Recurrent seizures (e.g. febrile convulsion, untreated epilepsy) 26. Irreversible secondary alterations of the reactive organ (e.g. emphysema, bronchiectasis) 27. For assessment the normal reference ranges of the central laboratory should be applied. If out of range, laboratory values greater than grade 1 according to the FDA Guidance for Industry (Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials) will lead to exclusion of the patient.
Medications: 28. Use of β-blockers (locally or systemically), ACE inhibitors 29. Contraindication for use of adrenalin (e.g. acute or chronic symptomatic coronary heartdisease, severe hypertension) 30. Completion or ongoing treatment with anti-IgE-antibodies (e.g. omalizumab) 31. Hypersensitivity to excipients of the investigational medical product Novo-Helisen Depot house dust mite preparation |
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E.5 End points |
E.5.1 | Primary end point(s) |
(descriptive safety variables) 1) Number, incidence, time of onset, type and intensity of AEs and serious adverse events (SAE) according to MedDRA primary system organ class (SOC) and preferred term 2) Number, incidence, time of onset, type and intensity of AEs and serious adverse events assessed as drug related (by investigator) according to MedDRA primary SOC and preferred term 3) Incidence and intensity of allergic systemic reactions after injections according to the World Allergy Organization (WAO) grading system 4) Number of patients reaching the maintenance dose without dose adjustment due to adverse events 5) Change of laboratory values (hematology, clinical chemistry and urinalysis) measured before and after the treatment phase 6) Change of vital signs and lung function measured before and after the treatment phase 7) Assessment of the overall tolerability by the investigator and the patient using a 5 point Likert scale (Likert 1932) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
endpoints 1, 2, 3: cumulative data from every visit except screening visit 1: for accelerated dose escalation group (G1): screening phone contact (week -2 - 0), weeks 0, 1, 2, 3, 4, 5, 7, 11, follow-up visit (week 13 - 15) for standard dose escalation group (G2): screening phone contact (week -2 - 0), weeks 0, 1, 2, 3, 4, 5, 6, 7, 8, 8, 10, 11, 12, 13, 15, 19, follow-up visit (week 21 - 23)
endpoint 4: for G1: week 5 for G2: 13
endpoints 5, 6: screening visit 1, follow-up visit (G1: week 13 - 15; G2: week 21 - 23)
endpoint 7: for G1: weeks 1, 2, 3, 4, 5, 7, 11, follow-up visit (week 13 - 15) for G2: weeks 1, 2, 3, 4, 5, 6, 7, 8, 8, 10, 11, 12, 13, 15, 19, follow-up visit (week 21 - 23) |
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E.5.2 | Secondary end point(s) |
exploratory enpoint: IgG4 specific for Dermatophagoides farinae and Dermatophagoides pteronyssinus |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Screening visit (week -14 - 0), follow-up visit (group 1: week 13 - 15; group 2: week 21 - 23) |
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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 | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 14 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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
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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 | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |