Clinical trial NCT02975479: 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
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Rhinitis, Allergic, Seasonal
Keywords: Hay fever
Pollen allergy
Allergic rhinitis
Lead sponsor: Karolinska Institutet
Sponsor class: OTHER
Collaborators: name: Skane University Hospital
name: Karolinska University Hospital
First posted: 2016-11-29
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Mean combined daily symptoms-and-medications-score
timeFrame: Peak pollen season (approximately 6 months after completed treatment) and entire pollen season (5-7 months after treatment).
Secondary outcomes:
measure: Mean total daily symptoms score
timeFrame: Peak pollen season (approximately 6 months after completed treatment) and entire pollen season (5-7 months after treatment).
measure: Mean total daily medications score
timeFrame: Peak pollen season (approximately 6 months after completed treatment) and entire pollen season (5-7 months after treatment).
measure: Change in subjective allergic symptoms following nasal allergen provocation
timeFrame: Before treatment, an average of 4 weeks after completed treatment and 6-9 months after treatment.
measure: Effects on quality of life
timeFrame: During peak pollen season which will be up to 6 months after completed treatment.
measure: Short term change of skin reactivity
timeFrame: Before treatment, an average of 4 weeks after completed treatment and 6-9 months after treatment.
measure: S-IgE Grass or Birch
timeFrame: Before treatment, approximately 4 weeks after completed treatment and 6-9 months after treatment
measure: S-IgG4 Grass or Birch
timeFrame: Before treatment, approximately 4 weeks after completed treatment and 6-9 months after treatment
measure: Registration of adverse event
timeFrame: From the first injection to 30 days after the last injections has been given
Other outcomes:
Locations:
city: Lund
country: Sweden
facility: Allergic Unit at the Department of Oto-Rhino-Laryngology at Skåne University Hospital Lund
city: Stockholm
country: Sweden
facility: ENT-department, Karolinska University Hospital Huddinge (ENT-department B51)
Study officials:
affiliation: Karolinska Institutet
name: Lars-Olaf Cardell, Professor
role: PRINCIPAL_INVESTIGATOR
References:
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.