Safety and Efficacy Study of Intralymphatic Allergen-specific Immunotherapy

Intralymphatic Allergen-specific Immunity as a New Administration Route for Treatment of Pollen-induced Allergic Diseases

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)

Study Overview

• Status: Completed
• Conditions: Allergic Rhinitis
• Intervention / Treatment: Drug: ALK Alutard Birch and/or 5-grasses; Drug: ALK Diluent

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.

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Sweden
  • Malmö, Sweden, 20502
    • Allergic Unit at the Department of Oto-Rhino-Laryngology at Skåne University Hospital Malmö

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 46 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ALK Alutard Birch and/or 5-grasses; 3 intralymphatic injections with dose 1000 SQ-U and dose interval 4 weeks.	Drug: ALK Alutard Birch and/or 5-grasses; 3 intralymphatic injections of 1000 SQ-U birch and/or grass allergen with 4 weeks interval. The substance used for the three intralymphatic injections is ALK-alutard SQ Betula verrucosa® and ALK-alutard SQ 5-grasses ® under ATC-code V01AA, V04CL and V07AB which is a depot formulation for subcutaneous use.; Other Names: ALK Alutard Betula Verrucosa and ALK Alutard 5-grasses
Placebo Comparator: ALK diluent; 3 intralymphatic injections with dose interval 4 weeks.	Drug: ALK Diluent; This placebo group will receive 3 injections of 0.3% human albumin instead of active substance; Other Names: Human albumin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in subjective allergic symptoms following nasal allergen provocation	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.	Before treatment, an average of 4 weeks after completed treatment and 6-9 months after treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Registration of adverse event		from the first injection to 30 days after the last injections has been given
Effects on quality of life	SNOT-22 questionnaire	During peak pollen season which will be up to 5 months (birch) and 6 months (grass) after completed treatment
Effects on quality of life	Juniper RQLQ questionnaires	During peak pollen season which will be up to 5 months (birch) and 6 months (grass) after completed treatment
Change in medicine consumption during pollen season	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.	6-9 months after treatment.
Change in symptoms at pollen season	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".	6-9 months after treatment.
Short term improvement of skin reactivity	Skin prick test	Before treatment, an average of 4 weeks after completed treatment and 6-9 months after treatment.
S-IgE Birch		Before treatment, approximately 4 weeks after completed treatment and 6-9 months after treatment
S-IgE Grass		Before treatment, approximately 4 weeks after completed treatment and 6-9 months after treatment
S-IgG4 Grass		Before treatment, approximately 4 weeks after completed treatment and 6-9 months after treatment
S-IgG4 Birch		Before treatment, approximately 4 weeks after completed treatment and 6-9 months after treatment

Collaborators and Investigators

• Sponsor: Karolinska Institutet
• Collaborators: Karolinska University Hospital; Skane University Hospital
• Investigators: Principal Investigator: Lars-Olaf Cardell, Prof, Karolinska Institutet

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: March 28, 2012
• First Submitted That Met QC Criteria: April 21, 2015
• First Posted (Estimate): April 22, 2015

Study Record Updates

• Last Update Posted (Actual): August 20, 2018
• Last Update Submitted That Met QC Criteria: August 16, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Hypersensitivity, Immediate; Otorhinolaryngologic Diseases; Respiratory Hypersensitivity; Hypersensitivity; Nose Diseases; Rhinitis; Rhinitis, Allergic
• Other Study ID Numbers: 2009-016815-39