Safety and tolerability of shortened up-dosing with Alutard SQ

Phase 1

Conditions: Allergic rhinoconjunctivitis induced by grass pollen, birch pollen and house dust mites
MedDRA version: 20.0Level: LLTClassification code 10001728Term: Allergic rhinoconjunctivitisSystem Organ Class: 100000004853
Therapeutic area: Diseases [C] - Ear, nose and throat diseases [C09]

Registration Number: EUCTR2017-000971-97-ES

Lead Sponsor: ALK Abelló A/S

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 320

Inclusion Criteria

I1. Written informed consent obtained before any trial related procedures are performed.
I2. Male or female aged 12–65 years at the time of consent.
I3. The subject fulfils one of the following criteria:
a. Male
b. Female, infertile
c. A female subject of child-bearing potential must have a negative pregnancy test and be willing to practise appropriate contraceptive methods until end of treatment visit.
I4. Documented clinically relevant history of moderate-to-severe grass pollen, birch pollen or house dust mite-induced rhinoconjunctivitis with or without controlled asthma despite having received treatment with symptomatic medication during the previous 2 grass, birch pollen seasons or 2 years, respectively.
I5. Positive SPT response to grass, birch or house dust mite allergens (wheal diameter = 3 mm) at screening corresponding with the allergy history (dominant allergy to grass, birch or house dust mites according to I4.).
I6. Documented positive IgE response (= IgE CAP class 2 or equivalent) in the allergy history to grass, birch or house dust mite allergens in the previous 2 years corresponding with the allergy history (dominant allergy to grass, birch or house dust mites according to I4.).
I7. The subject must be willing and able to comply with the trial protocol.
Are the trial subjects under 18? yes
Number of subjects for this age range: 80
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 240
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

E1. Asthma subjects at risk of exacerbation and/or with inadequate symptom control defined as the presence of: loss of symptom control within the last four weeks (e.g. increase in daytime symptoms, nightly wakening, increased need of medication, activity limitations), according to GINA guideline (2).
E2. Inadequately treated bronchial asthma or bronchial asthma with permanently impaired lung function (in adults: FEV1 < 70% of predicted value after adequate pharmacologic treatment, in adolescents: FEV1 < 80% of predicted value after adequate pharmacologic treatment)
E3. Irreversible respiratory damage such as emphysema or dilatation of the bronchi (bronchiectasis)
E4. Previous treatment with immunotherapy to an allergen related to the dominant allergy as defined in I4. (grass pollen, birch or house dust mite allergen or a cross-reacting allergen) within the past 5 years
E5. Ongoing treatment with any allergy immunotherapy product
E6. Has a history or current evidence of any condition, treatment, laboratory values out of range or other circumstance that in the opinion of the investigator are clinically relevant and might expose the subject to risk by participating in the trial, confound the results of the trial, or interfere with the subject’s participation for the full duration of the trial
E7. History of anaphylaxis with cardiorespiratory symptoms (immunotherapy, exercise induced, food allergy, drugs or an idiopathic reaction)
E8. History of recurrent (defined as 2 or more episodes) generalised urticaria during the last 2 years
E9. History of drug-induced (including allergy immunotherapy) facial angioedema or a family (parents and siblings) history of hereditary angioedema
E10. Any clinically relevant chronic disease (= 3 months duration) (e.g. cystic fibrosis, malignancy, malabsorption or malnutrition, renal or hepatic abnormality, or any other diseases that in the opinion of the investigator would interfere with the trial evaluations or the safety of the subjects)
E11. Systemic disease affecting the immune system (e.g. insulin-dependent diabetes, autoimmune disease, immune complex disease, or immune deficiency disease)
E12. Immunosuppressive treatment (ATC code L04 or L01) within 3 months prior to the screening visit
E13. Currently treated with tricyclic antidepressants, catecholamine-O-methyltransferase inhibitors and/or mono amine oxidase inhibitors
E14. Treatment with antidepressant medication with antihistaminic effect (e.g. doxepin, mianserine)
E15. Treatment with antipsychotic medications with antihistaminic effect (e.g. chlorpromazine, levomepromazine, clozapine, olanzapine, tioridazine)
E16. Treatment with anti-IgE drugs (e.g. omalizumab) within 130 days/5 half-lives of the drug, which ever the longest
E17. Treatment with systemic and/or topical ß-blockers
E18. Current participation in other clinical trials and/or use of an investigational drug within 30 days/5 half-lives of the drug, which ever the longest, prior to screening
E19. History of allergy, hypersensitivity or intolerance to an excipient of the investigational drug (except grass, birch or house dust mite allergens)
E20. Being immediate family of the investigator or trial staff, defined as the investigator's/staff’s spouse, parent, child, grandparent, or grandchild
E21. History of alcohol or drug abuse
E22. Lactating at screening

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The objective of the trial is to evaluate the safety and tolerability of a 7-injection up-dosing schedule with Alutard SQ 6-grasses and rye, birch and house dust mite mix compared with the 11-injection up-dosing schedule established for pollen allergens.;Secondary Objective: Not applicable;Primary end point(s): The primary endpoint is the number of investigational medicinal product (IMP)-related treatment emergent adverse events (TEAEs).;Timepoint(s) of evaluation of this end point: During the course of the trial.

Secondary Outcome Measures

Name	Time	Method
Timepoint(s) of evaluation of this end point: During the course of the trial;Secondary end point(s): Secondary endpoints are:<br>- Number of local reactions<br>- Number of systemic reactions<br>- Number of early/delayed systemic reactions<br>- Number of Adverse Events (AEs) leading to discontinuation<br>- Number of serious AEs (SAEs)<br>- Change in vital signs (resting blood pressure, heart rate) from preinjection to 60-minutes post-injection at each IMP injection visit<br>- Percentage of IMP injections with a decrease in peak expiratory flow (PEF) values > 20% from pre-injection to 60-minutes post-injection for each dose<br>- Changes observed in physical examination from screening to last planned assessment

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