Intralymphatic Immunotherapy in Increasing Doses, Substudy

Intralymphatic Immunotherapy in Increasing Doses up to 10 000 SQ-U - a Human Randomized Clinical Trial. Substudy.

The study evaluates the safety and effect of intralymphatic allergen specific immunotherapy in increasing doses. Patients with allergy to grass or birch will be treated with three intralymphatic injections in an up-dosing protocol; 1000 SQ-U, 3000 SQ-U and 10 000 SQ-U, or placebo.

***IMPORTANT INFORMATION!*** The up-dosing protocol is changed due to adverse events at 5000 SQ-U. One patient had general utricaria 15 minutes after injection (moderate reaction). One patient had a serious adverse event with anaphylactic reaction 6 minutes after intralymphatic injection. (1000 SQ-U and 3000 SQ-U have been given with no serious adverse events.) New regimen: 1000 SQ-U, 3000 SQ-U, 3000 SQ-U.

Study Overview

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

Detailed Description

40 patients with seasonal allergic rhinitis will be recruited. Study subjects are randomized to intralymphatic injections with placebo or ALK Alutard 5-grasses or birch. Injections are given with 4-5 (-7) weeks interval.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Sweden
  • Lund, Sweden, 221 85
    • Allergic Unit at the Department of Oto-Rhino-Laryngology at Skåne University Hospital Lund
  • Stockholm, Sweden, 141 86
    • ENT-department, Karolinska University Hospital Huddinge (ENT-department B51)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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
Placebo Comparator: Intralymphatic placebo injections; ALK Diluent, ATC-code V07AB. 3 injections with 4-7 weeks interval.	Drug: ALK Diluent; Other Names: 0,3% human albumin. ATC-code V07AB
Active Comparator: Intralymphatic active injections; ATC-code V01AA02. 3 injections with 4-7 weeks interval in an up-dosing protocol; 1000 SQ-U, 3000 SQ-U, 10000 SQ-U. ***IMPORTANT INFORMATION! The up-dosing protocol is changed due to an adverse event at the last injection. New regimen: 1000 SQ-U, 3000 SQ-U, 3000 SQ-U. ***	Drug: ALK Alutard SQ 5-grasses or ALK Alutard Birch; Depot formulation of relevant allergen adsorbed to aluminium hydroxide in a suspension.; Other Names: Allergen, grass pollen. ATC-code V01AA02 or V01AA05

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean combined daily symptoms-and-medications-score	Daily scoring of rhinoconjunctivitis symptoms (6 questions, 4-point scale) and medication use (oral or topical antihistamines, intranasal corticosteroids, oral corticosteroids).	Peak pollen season (approximately 6 months after completed treatment) and entire pollen season (5-7 months after treatment).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean total daily symptoms score	Daily scoring of rhinoconjunctivitis symptoms (6 questions, 4-point scale)	Peak pollen season (approximately 6 months after completed treatment) and entire pollen season (5-7 months after treatment).
Mean total daily medications score	Daily scoring of medication use (oral or topical antihistamines, intranasal corticosteroids, oral corticosteroids).	Peak pollen season (approximately 6 months after completed treatment) and entire pollen season (5-7 months after treatment).
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.
Effects on quality of life	Juniper Rhinitis quality of life questionnaire (RQLQ) questionnaires	During peak pollen season which will be up to 6 months after completed treatment.
Short term change of skin reactivity	Skin prick test	Before treatment, an average of 4 weeks after completed treatment and 6-9 months after treatment.
S-IgE Grass or Birch		Before treatment, approximately 4 weeks after completed treatment and 6-9 months after treatment
S-IgG4 Grass or Birch		Before treatment, approximately 4 weeks after completed treatment and 6-9 months after treatment
Registration of adverse event		From the first injection to 30 days after the last injections has been given

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Hellkvist L, Hjalmarsson E, Weinfeld D, Dahl A, Karlsson A, Westman M, Lundkvist K, Winqvist O, Georen SK, Westin U, Cardell LO. High-dose pollen intralymphatic immunotherapy: Two RDBPC trials question the benefit of dose increase. Allergy. 2022 Mar;77(3):883-896. doi: 10.1111/all.15042. Epub 2021 Aug 29.

Study record dates

Study Major Dates

• Study Start: May 1, 2016
• Primary Completion (Actual): June 20, 2022
• Study Completion (Actual): June 20, 2022

Study Registration Dates

• First Submitted: November 24, 2016
• First Submitted That Met QC Criteria: November 28, 2016
• First Posted (Estimate): November 29, 2016

Study Record Updates

• Last Update Posted (Actual): June 24, 2022
• Last Update Submitted That Met QC Criteria: June 22, 2022
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Hay fever; Pollen allergy; Allergic rhinitis
• 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; Rhinitis, Allergic, Seasonal
• Other Study ID Numbers: 2015-001259-63 substudy

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No