Assessment of safety and clinical tolerability of increasing doses of the investigational medicinal product hdmASIT+TM injected under the skin of patients suffering from perennial allergic rhinitis

Phase 1

• Conditions: Treatment of house dust mite induced allergic rhinoconjunctivitis; MedDRA version: 20.0Level: LLTClassification code 10001728Term: Allergic rhinoconjunctivitisSystem Organ Class: 100000014962; Therapeutic area: Diseases [C] - Ear, nose and throat diseases [C09]

• Registration Number: EUCTR2016-000557-13-DE
• Lead Sponsor: ASIT biotech S.A.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-04-05
• Last Update Posted: 21 August 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

•Signed and dated Informed Consent Form by a legally competent patient
•Female or male patients aged 18–64 years
•Being in good physical and mental health
•Normal hepatic and renal function defined as per laboratory values of blood samplings according to local laboratory ranges
•For females: non-pregnant, non-lactating with adequate contraception or females unable to bear children (i.e. tubal ligation, hysterectomy, or post-menopausal (defined as a minimum of one year since the last menstrual period))
•Having the diagnosis of allergy based on all the following criteria:
A medical history of moderate to severe allergic rhinoconjunctivitis for house dust mite for at least 12 months (definition of allergy severity according to ARIA (Bousquet et al 2001))
A positive skin prick test (SPT - wheal diameter = 3 mm) to house dust mite Dermatophagoides pteronyssinus, positive control (histamine) wheal = 3 mm, negative control (NaCl) wheal < 2 mm
Specific IgE against house dust mite Dermatophagoides pteronyssinus > 0.7 kU/L
Positive response to CPT with at least 30,000 SQ-E/mL of Dermatophagoides pteronyssinus solution
•Having been treated with anti-allergic medication for at least 12 months prior to enrollment
•For asthmatic patients: confirmed diagnosis of controlled asthma according to Global Initiative for Asthma (GINA) guidelines (steps 1-3, GINA 2014), FEV1 = 80% of the patient's reference value (ECSC)

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Patients must not meet any of the following non-inclusion criteria in order to participate in this study:
•Simultaneous participation in other clinical trials or previous participation within 30 days before inclusion
•Previous immunotherapy with house dust mite allergens within the last 5 years
•Ongoing immunotherapy with house dust mite allergens or any other allergens
•Being in any relationship or dependence with the Sponsor, CRO and/or Investigator
•Inability to understand instructions/study documents
•History of severe systemic reactions and/or anaphylaxis, including to food (e.g. peanut, marine animals) or to Hymenoptera venom (e.g. bee, wasp stings) or to medication (e.g. penicillin), etc.
•History of hypersensitivity to the excipients of the investigational product or placebo
•Partly controlled or uncontrolled asthma according to GINA guidelines (GINA 2014)
•Chronic asthma or emphysema, particularly with a forced expiratory volume in 1 second (FEV1) < 80% of the patient’s reference value (ECSC)
•History of a respiratory tract infection and/or exacerbation of asthma within 4 weeks before the screening
•Patients symptomatic to any inhaled allergens circulating during the study period (e.g. Mugwort, Ragweed, Alternaria, etc.) documented by history AND sIgE AND SPT
•Patients symptomatic to any other perennial inhaled allergens (cat, dog) to which are regularly exposed and documented by history AND sIgE AND SPT
•History of significant renal disease or chronic hepatic disease
•Malignant active disease (ongoing or in within the past five years)
•Diagnosed with severe autoimmune disease
•Any chronic disease which may impair the patient’s ability to participate in the trial (e.g. severe congestive heart failure, active gastric ulcer, inflammatory bowel disease, uncontrolled diabetes mellitus, etc.)
•Intake of beta-blockers/acetylcholinesterase inhibitors medication
•Intake of antidepressant drugs with potent antihistamine properties i.e. tricyclic antidepressants (e.g. doxepin, amitriptyline, desipramine, imipramine, etc.)
•Administration or planned administration of anti-IgE antibodies, mast cell stabilizers or anti-leukotriene agents
•Having any contraindication for CPT testing
•Having any contraindication for the use of adrenaline
•Known positive serology for Human Immunodeficiency Virus-1/2, Hepatitis B Virus or Hepatitis C Virus
•Female who are pregnant, lactating, or of child-bearing potential and not using adequate contraceptive method
•Administration of corticosteroids (oral, topic or nasal) or of anti-histaminic drugs within time period preceding the trial (screening visit), as defined in the protocol with the exception of routine (previously prescribed) controller medication for asthmatic patients
•Planned vaccination during the entire study period (e.g. against flu, pneumococcal, etc) – refer to the non authorized mediation section
•No laboratory values clinically relevant greater than grade 2 according to the FDA Guidance for Industry for preventive Vaccine Trials (FDA 2007) at screening visit *
•Patients for who the investigator believes will not comply with the study protocol (patients with known alcoholism or drug abuse or with a history of a serious psychiatric disorder as well as patients unwilling to give informed consent or to abide by the requirements of the protocol)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective is to assess the safety and clinical tolerability of hdmASIT+TM treatment administered subcutaneously to patients with house dust mite related allergic rhinoconjunctivitis.;Secondary Objective: The secondary objectives are:<br>To assess the impact on the immunological status of the patients and clinical impact of hdmASIT+TM comparing actively treated and placebo patients.<br>;Primary end point(s): Safety and clinical tolerability of hdmASIT+TM treatment assessed by solicited adverse events: local reactions at the injection site (swelling and redness) and allergic systemic reactions after investigational product administration;Timepoint(s) of evaluation of this end point: Local reactions at the injection site (swelling and redness) and allergic systemic reactions after investigational product administration were evaluated after treatment at visit 2 to 9.