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Safety and Efficacy Study of Intralymphatic Allergen-specific Immunotherapy

Phase 2
Completed
Conditions
Allergic Rhinitis
Interventions
Drug: ALK Alutard Birch and/or 5-grasses
Drug: ALK Diluent
Registration Number
NCT02423707
Lead Sponsor
Karolinska Institutet
Brief Summary

Allergen-specific immunotherapy (ASIT) is commonly used to treat patients with allergic rhino-conjunctivitis and asthma, and it is the only proven treatment that affects the long-term development of allergic rhinitis and asthma. The current treatment regime of ASIT requires numerous subcutaneous allergen injections and takes several years to complete. Hence, there is a need to develop more convenient protocols for induction of allergen tolerance.

Emerging evidence suggest that by targeting of antigen presenting cells within the lymph nodes the immunogenicity of the allergen can be enhanced and the number of injections can be reduced.

The purpose of this study is to evaluate whether intralymphatic administration of ASIT is a safe and effective treatment for patients with pollen-induced allergic rhinitis. The long term goal is to provide a base for a more efficient administration of ASIT, which will reduce both the dose necessary and the number of clinic visits associated with the conventional subcutaneous ASIT.

The investigators will make an attempt to reproduce the results of a recent human study of intralymphatic ASIT (clinicaltrials.gov; NCT00470457) in a Swedish clinical setting.

The first part of the study is completed and published (PMID: 23374268)

Detailed Description

In the first part of the study safety and clinical efficacy of ALK Alutard Birch or 5-grass have been evaluated in a RCT with 50 patients. Active patients recieve 3 injections with 1000 SQ-U ALK Alutard or 5-grasses in a lymph node in the groin. Dose interval 4 weeks. This part of the study is completed and published (PMID: 23374268)

In the second part of the study 60 patients participates in a RCT with intralymphatic injections with both ALK Alutard Birch AND ALK Alutard 5-grasses. The injections are given intralymphatically with one allergen in each groin with 30 minutes observation between injections. Dose and dose interval are the same as in the first part of the study; the active group recieves 1000 SQ-U ALK Alutard Birch in right groin and 1000 SQ-U 5-grasses in left groin. The injections are given 3 times with 4 weeks interval. Enrollment and treatment is completed and the results will be evaluated in the autumn 2015.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
110
Inclusion Criteria
  • Age 18-50,
  • Seasonal allergic symptoms for birch and/or grass verified by skin prick test,
  • Accepted informed consent
Read More
Exclusion Criteria
  • Pregnancy or nursing
  • Autoimmune or collagen disease (known)
  • Cardiovascular disease
  • Perennial pulmonary disease
  • Hepatic disease
  • Renal disease
  • Cancer
  • Any medication with a possible side-effect of interfering with the immune response
  • Previous immuno- or chemotherapy
  • Chronic diseases
  • Other upper airway disease (non-allergic sinusitis, nasal polyps, chronic obstructive and restrictive lung disease)
  • Disease or conditions rendering the treatment of anaphylactic reactions difficult (symptomatic coronary heart diseases, severe arterial hypertension and treatment with β-blockers)
  • Major metabolic disease
  • Known or suspected allergy to the study product
  • Alcohol or drug abuse
  • Mental incapability of coping with the study
  • Withdrawal of informed consent
Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
ALK Alutard Birch and/or 5-grassesALK Alutard Birch and/or 5-grasses3 intralymphatic injections with dose 1000 SQ-U and dose interval 4 weeks.
ALK diluentALK Diluent3 intralymphatic injections with dose interval 4 weeks.
Primary Outcome Measures
NameTimeMethod
Change in subjective allergic symptoms following nasal allergen provocationBefore treatment, an average of 4 weeks after completed treatment and 6-9 months after treatment.

The study subjects will be intranasally challenged with allergen and symptom score questionnaires are filled out pre-provocation and 5, 10 and 30 min post-provocation.

Secondary Outcome Measures
NameTimeMethod
Effects on quality of lifeDuring peak pollen season which will be up to 5 months (birch) and 6 months (grass) after completed treatment

Juniper RQLQ questionnaires

Change in symptoms at pollen season6-9 months after treatment.

After the pollen season at the 6-9 months follow up patients recall the pollen season and rates the improvement on an arbitrary scale ranging 0-10 with 0 as "no improvement at all" and 10 "total symptom relief".

Registration of adverse eventfrom the first injection to 30 days after the last injections has been given
Change in medicine consumption during pollen season6-9 months after treatment.

After the pollen season patients report to what extension they have been using medications; more, the same or less. The mediacations asked about are antihistamine tablets, antihistamine eye drops, nasal steroid, steroid tablets, b2-bronchodilator inhalation, leucotrien receptor antagonist, nasal or ocular sodium chromoglycates.

S-IgE BirchBefore treatment, approximately 4 weeks after completed treatment and 6-9 months after treatment
Short term improvement of skin reactivityBefore treatment, an average of 4 weeks after completed treatment and 6-9 months after treatment.

Skin prick test

S-IgE GrassBefore treatment, approximately 4 weeks after completed treatment and 6-9 months after treatment
S-IgG4 GrassBefore treatment, approximately 4 weeks after completed treatment and 6-9 months after treatment
S-IgG4 BirchBefore treatment, approximately 4 weeks after completed treatment and 6-9 months after treatment

Trial Locations

Locations (1)

Allergic Unit at the Department of Oto-Rhino-Laryngology at Skåne University Hospital Malmö

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Malmö, Sweden

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