Intralymphatic Immunotherapy in Increasing Doses, Substudy
Primary Purpose
Rhinitis, Allergic, Seasonal
Status
Completed
Phase
Phase 2
Locations
Sweden
Study Type
Interventional
Intervention
ALK Diluent
ALK Alutard SQ 5-grasses or ALK Alutard Birch
Sponsored by
About this trial
This is an interventional treatment trial for Rhinitis, Allergic, Seasonal focused on measuring Hay fever, Pollen allergy, Allergic rhinitis
Eligibility Criteria
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
Sites / Locations
- Allergic Unit at the Department of Oto-Rhino-Laryngology at Skåne University Hospital Lund
- ENT-department, Karolinska University Hospital Huddinge (ENT-department B51)
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Active Comparator
Arm Label
Intralymphatic placebo injections
Intralymphatic active injections
Arm Description
ALK Diluent, ATC-code V07AB. 3 injections with 4-7 weeks interval.
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. ***
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
Mean total daily symptoms score
Daily scoring of rhinoconjunctivitis symptoms (6 questions, 4-point scale)
Mean total daily medications score
Daily scoring of medication use (oral or topical antihistamines, intranasal corticosteroids, oral corticosteroids).
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.
Effects on quality of life
Juniper Rhinitis quality of life questionnaire (RQLQ) questionnaires
Short term change of skin reactivity
Skin prick test
S-IgE Grass or Birch
S-IgG4 Grass or Birch
Registration of adverse event
Full Information
NCT ID
NCT02975479
First Posted
November 24, 2016
Last Updated
June 22, 2022
Sponsor
Karolinska Institutet
Collaborators
Skane University Hospital, Karolinska University Hospital
1. Study Identification
Unique Protocol Identification Number
NCT02975479
Brief Title
Intralymphatic Immunotherapy in Increasing Doses, Substudy
Official Title
Intralymphatic Immunotherapy in Increasing Doses up to 10 000 SQ-U - a Human Randomized Clinical Trial. Substudy.
Study Type
Interventional
2. Study Status
Record Verification Date
October 2020
Overall Recruitment Status
Completed
Study Start Date
May 2016 (undefined)
Primary Completion Date
June 20, 2022 (Actual)
Study Completion Date
June 20, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Karolinska Institutet
Collaborators
Skane University Hospital, Karolinska University Hospital
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rhinitis, Allergic, Seasonal
Keywords
Hay fever, Pollen allergy, Allergic rhinitis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Intralymphatic placebo injections
Arm Type
Placebo Comparator
Arm Description
ALK Diluent, ATC-code V07AB. 3 injections with 4-7 weeks interval.
Arm Title
Intralymphatic active injections
Arm Type
Active Comparator
Arm Description
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. ***
Intervention Type
Drug
Intervention Name(s)
ALK Diluent
Other Intervention Name(s)
0,3% human albumin. ATC-code V07AB
Intervention Type
Drug
Intervention Name(s)
ALK Alutard SQ 5-grasses or ALK Alutard Birch
Other Intervention Name(s)
Allergen, grass pollen. ATC-code V01AA02 or V01AA05
Intervention Description
Depot formulation of relevant allergen adsorbed to aluminium hydroxide in a suspension.
Primary Outcome Measure Information:
Title
Mean combined daily symptoms-and-medications-score
Description
Daily scoring of rhinoconjunctivitis symptoms (6 questions, 4-point scale) and medication use (oral or topical antihistamines, intranasal corticosteroids, oral corticosteroids).
Time Frame
Peak pollen season (approximately 6 months after completed treatment) and entire pollen season (5-7 months after treatment).
Secondary Outcome Measure Information:
Title
Mean total daily symptoms score
Description
Daily scoring of rhinoconjunctivitis symptoms (6 questions, 4-point scale)
Time Frame
Peak pollen season (approximately 6 months after completed treatment) and entire pollen season (5-7 months after treatment).
Title
Mean total daily medications score
Description
Daily scoring of medication use (oral or topical antihistamines, intranasal corticosteroids, oral corticosteroids).
Time Frame
Peak pollen season (approximately 6 months after completed treatment) and entire pollen season (5-7 months after treatment).
Title
Change in subjective allergic symptoms following nasal allergen provocation
Description
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.
Time Frame
Before treatment, an average of 4 weeks after completed treatment and 6-9 months after treatment.
Title
Effects on quality of life
Description
Juniper Rhinitis quality of life questionnaire (RQLQ) questionnaires
Time Frame
During peak pollen season which will be up to 6 months after completed treatment.
Title
Short term change of skin reactivity
Description
Skin prick test
Time Frame
Before treatment, an average of 4 weeks after completed treatment and 6-9 months after treatment.
Title
S-IgE Grass or Birch
Time Frame
Before treatment, approximately 4 weeks after completed treatment and 6-9 months after treatment
Title
S-IgG4 Grass or Birch
Time Frame
Before treatment, approximately 4 weeks after completed treatment and 6-9 months after treatment
Title
Registration of adverse event
Time Frame
From the first injection to 30 days after the last injections has been given
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lars-Olaf Cardell, Professor
Organizational Affiliation
Karolinska Institutet
Official's Role
Principal Investigator
Facility Information:
Facility Name
Allergic Unit at the Department of Oto-Rhino-Laryngology at Skåne University Hospital Lund
City
Lund
ZIP/Postal Code
221 85
Country
Sweden
Facility Name
ENT-department, Karolinska University Hospital Huddinge (ENT-department B51)
City
Stockholm
ZIP/Postal Code
141 86
Country
Sweden
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
34379802
Citation
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.
Results Reference
derived
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Intralymphatic Immunotherapy in Increasing Doses, Substudy
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