The Safety and Efficacy of Intralymphatic Immunotherapy in Pollen Allergic Adolescents and Young Adults With Asthma

NCT03394508 | Completed Phase 2 Results

• 1 other identifier: DNR 2012/701 EPN Lund
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

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)".

Conditions

Rhinitis; Asthma; Allergy

Outcome Measures

Primary Outcomes (1)

• Change in Symptoms Score After Nasal Allergen Challenge

  0,1 ml of ALK Aquagen birch or timothy 10 000 SQU/ml is deposited in each nostril and allergy symptoms are recorded. Symptoms during NPTs were scored according to the Lebel scoring scale. Symtom scores at 5, 15, and 30 minutes after nasal administration of the allergenextract were summed to represent the symptom-score at each nasal challenge (at inclusion, 12 months after inclusion and for the active patients 24 months after inclusion). The scoring system identifies nasal, eye, and ear symptoms: rhinorrhea, nasal pruritus, nasal congestion, ocular pruritus, watery eyes, and itchy ears, each graded on a scale from 0 to 3 points, and a total score was summarized after subtracting the starting score (min score is 0 and maximum score is 54 + the number of sneezes). Higher scores mean worse outcome.

  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 (9)

• Change on Visual Analogue Scale (VAS

  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).

• Change in Quality of Life

  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).

• Change in Allergen-specific Serum Immunoglobulin E (IgE) Levels Compared to Before Treatment

  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).

• Change in Asthma Symptom Scores

  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).

• Change in Pulmonary Function Measurement (Spirometry)

  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).

Study Arms (2)

Placebo

PLACEBO COMPARATOR

ALK diluent 0,3% human albumin'

Drug: ALK diluent 0,3% human albumin

Active treatment

EXPERIMENTAL

Intervention: Drug ALK Alutard birch or 5-grasses. Grass pollen suspension or birch pollen suspension

Drug: ALK Alutard birch or 5-grasses

Interventions

ALK Alutard birch or 5-grasses DRUG

Intralymphatic injection with 1000 units. 3 injections with 4-5 weeks interval (0,1 ml) and one additional booster injection with 1000 units before the second pollen season.

Also known as: ALK Alutard birch pollen or ALK Alutard grass pollen

Active treatment

ALK diluent 0,3% human albumin DRUG

Intralymphatic injection with 0.1 ml. 3 injections with 4-5 weeks interval

Also known as: Human albumin

Placebo

Eligibility Criteria

• Age: 16 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Karolinska Institutet: lead

Related Publications (5)

• 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.

  PMID: 26706294 BACKGROUND

• 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.

  PMID: 24035151 BACKGROUND

• 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.

  PMID: 23374268 BACKGROUND

• 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.

  PMID: 22464647 BACKGROUND

• 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.

  PMID: 26817454 RESULT

MeSH Terms

Conditions

Rhinitis; Asthma; Hypersensitivity

Interventions

Serum Albumin, Human

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Nose Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Immune System Diseases

Intervention Hierarchy (Ancestors)

Serum Albumin; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Blood Proteins

Limitations and Caveats

a=active,p=placebo:No booster dose and no follow-up (1a), No NPTs before (1a) and at follow up (1a, 1p), No methacholine, quality of life in the second follow-up (1a). No symptoms and medication scores (3a, 3p), No spirometry at follow-up (1a,1p).

Results Point of Contact

• Title: Jon Konradsen
• Organization: Karolinska Institutet

jon.konradsen@ki.se

+46704242058

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 6, 2017
• First Posted: January 9, 2018
• Study Start: January 1, 2013
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: September 28, 2020
• Results First Posted: September 28, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share