Clinical trial NCT02423707: Safety and Efficacy Study of Intralymphatic Allergen-specific Immunotherapy
Official title: Intralymphatic Allergen-specific Immunity as a New Administration Route for Treatment of Pollen-induced Allergic Diseases
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Allergic Rhinitis
Lead sponsor: Karolinska Institutet
Sponsor class: OTHER
Collaborators: name: Skane University Hospital
name: Karolinska University Hospital
First posted: 2015-04-22
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* Age 18-50,
* Seasonal allergic symptoms for birch and/or grass verified by skin prick test,
* Accepted informed consent

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

Primary outcomes:
measure: Change in subjective allergic symptoms following nasal allergen provocation
timeFrame: Before treatment, an average of 4 weeks after completed treatment and 6-9 months after treatment.
Secondary outcomes:
measure: Registration of adverse event
timeFrame: from the first injection to 30 days after the last injections has been given
measure: Effects on quality of life
timeFrame: During peak pollen season which will be up to 5 months (birch) and 6 months (grass) after completed treatment
measure: Effects on quality of life
timeFrame: During peak pollen season which will be up to 5 months (birch) and 6 months (grass) after completed treatment
measure: Change in medicine consumption during pollen season
timeFrame: 6-9 months after treatment.
measure: Change in symptoms at pollen season
timeFrame: 6-9 months after treatment.
measure: Short term improvement of skin reactivity
timeFrame: Before treatment, an average of 4 weeks after completed treatment and 6-9 months after treatment.
measure: S-IgE Birch
timeFrame: Before treatment, approximately 4 weeks after completed treatment and 6-9 months after treatment
measure: S-IgE Grass
timeFrame: Before treatment, approximately 4 weeks after completed treatment and 6-9 months after treatment
measure: S-IgG4 Grass
timeFrame: Before treatment, approximately 4 weeks after completed treatment and 6-9 months after treatment
measure: S-IgG4 Birch
timeFrame: Before treatment, approximately 4 weeks after completed treatment and 6-9 months after treatment
Other outcomes:
Locations:
city: Malmö
country: Sweden
facility: Allergic Unit at the Department of Oto-Rhino-Laryngology at Skåne University Hospital Malmö
Study officials:
affiliation: Karolinska Institutet
name: Lars-Olaf Cardell, Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: Senti G, Prinz Vavricka BM, Erdmann I, Diaz MI, Markus R, McCormack SJ, Simard JJ, Wuthrich B, Crameri R, Graf N, Johansen P, Kundig TM. Intralymphatic allergen administration renders specific immunotherapy faster and safer: a randomized controlled trial. Proc Natl Acad Sci U S A. 2008 Nov 18;105(46):17908-12. doi: 10.1073/pnas.0803725105. Epub 2008 Nov 10.