Clinical trial NCT03394508: The Safety and Efficacy of Intralymphatic Immunotherapy in Pollen Allergic Adolescents and Young Adults With Asthma
Official title: The Safety and Efficacy of Intralymphatic Immunotherapy in Pollen Allergic Adolescents and Young Adults With Asthma: A Randomized Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Rhinitis
Asthma
Allergy
Lead sponsor: Karolinska Institutet
Sponsor class: OTHER
First posted: 2018-01-09
Enrollment: 30
Sex: ALL
Minimum age (years): 16
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study evaluates the safety and efficacy of intralymphatic allergen-specific immunotherapy given to adolescents and young adults who are allergic to grass or birch pollen and have mild or moderate asthma. Patients will be treated with three intralymphatic injections; 1000 SQ-U x3 with 4-5 weeks interval, or placebo with 4-5 weeks interval. The patients receiving treatment will be given a fourth injection one year after the initial injections. The study is conducted in collaboration between Professor Lars Olof Cardell (ENT), prof Gunilla Hedlin (Pediatrics) and prof Marianne van Hage (Immunology)".

Detailed description: 30 patients with seasonal allergic rhinitis due to birch or grass pollen are included. Study subjects are randomized to intralymphatic injections with placebo or ALK Alutard 5-grasses / birch or placebo. The patients receiving treatment will be given a fourth injection one year after the initial injections.

Eligibility criteria: Inclusion Criteria:

* Allergic rhinitis due to grass or birch pollen
* Mild to moderate asthma with a positive methacholine challenge
* Accepted and signed informed consent.

Exclusion Criteria:

* Previously subcutaneous immunotherapy (SCIT) with total symptom relief.
* Previously SCIT but no symptom improvement at all.
* Sensitizations to house dust mite or furry animals, with ongoing exposure and symptoms.
* Severe atopic dermatitis.
* Patients with significant diseases other than allergic rhinitis. A significant disease is defined as a disease which in the opinion of the investigator may either put the patient at risk because of participation in the study or a disease which may influence the results of the study or the patient's ability to participate in the study.
* Patients with a respiratory tract infection in the past 4 weeks prior to Visit 2.
* Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception (i.e., oral contraceptives, intrauterine devices, diaphragm, or subdermal implants).
* Known autoimmune or collagen disease
* Cardiovascular disease
* Hepatic disease
* Known renal insufficiency
* Cancer
* Hematologic disease
* Chronic infectious disease
* Any medication with a possible side-effect of interfering with the immune response
* Previous immuno- or chemotherapy
* 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
* Obesity with BMI \> 30 since subcutaneous fat makes ultrasound imaging of lymph nodes harder which may risk the correct placement of injection.
* Patients who, in the opinion of the investigator, abuse alcohol or drugs within 2 years prior to Visit 1.
* Patients who have taken an investigational drug within 1 month or six half lives, whichever is greater, prior to Visit 1.
* Mental incapability of coping with the study
* Withdrawal of informed consent

Primary outcomes:
measure: Change in Symptoms Score After Nasal Allergen Challenge
timeFrame: At inclusion (pre-treatment), 12 months after inclusion (after first pollen season) and for the active treated patients 24 months after inclusion (after the second pollen season).
Secondary outcomes:
measure: Change on Visual Analogue Scale (VAS
timeFrame: At inclusion (pre-treatment), 12 months after inclusion (after first pollen season) and for the active treated patients 24 months after inclusion (after the second pollen season).
measure: Change in Quality of Life
timeFrame: At inclusion (pre-treatment), 12 months after inclusion (after first pollen season) and for the active treated patients 24 months after inclusion (after the second pollen season).
measure: Change in Allergen-specific Serum Immunoglobulin E (IgE) Levels Compared to Before Treatment
timeFrame: At inclusion (pre-treatment), 12 months after inclusion (after first pollen season) and for the active treated patients 24 months after inclusion (after the second pollen season).
measure: Change in Asthma Symptom Scores
timeFrame: At inclusion (pre-treatment), 12 months after inclusion (after first pollen season) and for the active treated patients 24 months after inclusion (after the second pollen season).
measure: Change in Pulmonary Function Measurement (Spirometry)
timeFrame: At inclusion (pre-treatment), 12 months after inclusion (after first pollen season) and for the active treated patients 24 months after inclusion (after the second pollen season).
measure: Changes in Airway Inflammation Assessed by Exhaled Nitric Oxide
timeFrame: At inclusion (pre-treatment), 12 months after inclusion (after first pollen season) and for the active treated patients 24 months after inclusion (after the second pollen season).
measure: Change in Symptom and Medication-score
timeFrame: At inclusion (pre-treatment), 12 months after inclusion (after first pollen season) and for the active treated patients 24 months after inclusion (after the second pollen season).
measure: Changes in Response to a Bronchial Challenge With Methacholine
timeFrame: At inclusion (pre-treatment), 12 months after inclusion (after first pollen season) and for the active treated patients 24 months after inclusion (after the second pollen season).
measure: Change in Allergen-specific Serum Immunoglobulin (Ig) G and Ig4 Levels Compared to Before Treatment
timeFrame: At inclusion (pre-treatment), 12 months after inclusion (after first pollen season) and for the active treated patients 24 months after inclusion (after the second pollen season).
Other outcomes:
Locations:
Study officials:
References:
citation: Patterson AM, Bonny AE, Shiels WE 2nd, Erwin EA. Three-injection intralymphatic immunotherapy in adolescents and young adults with grass pollen rhinoconjunctivitis. Ann Allergy Asthma Immunol. 2016 Feb;116(2):168-70. doi: 10.1016/j.anai.2015.11.010. Epub 2015 Dec 17. No abstract available.
citation: Witten M, Malling HJ, Blom L, Poulsen BC, Poulsen LK. Is intralymphatic immunotherapy ready for clinical use in patients with grass pollen allergy? J Allergy Clin Immunol. 2013 Nov;132(5):1248-1252.e5. doi: 10.1016/j.jaci.2013.07.033. Epub 2013 Sep 13. No abstract available.
citation: Hylander T, Latif L, Petersson-Westin U, Cardell LO. Intralymphatic allergen-specific immunotherapy: an effective and safe alternative treatment route for pollen-induced allergic rhinitis. J Allergy Clin Immunol. 2013 Feb;131(2):412-20. doi: 10.1016/j.jaci.2012.10.056.
citation: Senti G, Crameri R, Kuster D, Johansen P, Martinez-Gomez JM, Graf N, Steiner M, Hothorn LA, Gronlund H, Tivig C, Zaleska A, Soyer O, van Hage M, Akdis CA, Akdis M, Rose H, Kundig TM. Intralymphatic immunotherapy for cat allergy induces tolerance after only 3 injections. J Allergy Clin Immunol. 2012 May;129(5):1290-6. doi: 10.1016/j.jaci.2012.02.026. Epub 2012 Mar 30.
citation: Hylander T, Larsson O, Petersson-Westin U, Eriksson M, Kumlien Georen S, Winqvist O, Cardell LO. Intralymphatic immunotherapy of pollen-induced rhinoconjunctivitis: a double-blind placebo-controlled trial. Respir Res. 2016 Jan 27;17:10. doi: 10.1186/s12931-016-0324-9.