Intralymphatic Immunotherapy in Increasing Doses, Substudy

Sponsor

Karolinska Institutet (Other)

Overall Status

Completed

CT.gov ID

NCT02975479

Collaborator

Skane University Hospital (Other), Karolinska University Hospital (Other)

Enrollment

Locations

Arms

73.6

Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Rhinitis, Allergic, Seasonal	Drug: ALK Diluent Drug: ALK Alutard SQ 5-grasses or ALK Alutard Birch	Phase 2/Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

May 1, 2016

Actual Primary Completion Date :

Jun 20, 2022

Actual Study Completion Date :

Jun 20, 2022

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Mean combined daily symptoms-and-medications-score [Peak pollen season (approximately 6 months after completed treatment) and entire pollen season (5-7 months after treatment).]
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 [Peak pollen season (approximately 6 months after completed treatment) and entire pollen season (5-7 months after treatment).]
Daily scoring of rhinoconjunctivitis symptoms (6 questions, 4-point scale)
Mean total daily medications score [Peak pollen season (approximately 6 months after completed treatment) and entire pollen season (5-7 months after treatment).]
Daily scoring of medication use (oral or topical antihistamines, intranasal corticosteroids, oral corticosteroids).
Change in subjective allergic symptoms following nasal allergen provocation [Before treatment, an average of 4 weeks after completed treatment and 6-9 months after treatment.]
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 [During peak pollen season which will be up to 6 months after completed treatment.]
Juniper Rhinitis quality of life questionnaire (RQLQ) questionnaires
Short term change of skin reactivity [Before treatment, an average of 4 weeks after completed treatment and 6-9 months after treatment.]
Skin prick test
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Allergic Unit at the Department of Oto-Rhino-Laryngology at Skåne University Hospital Lund	Lund		Sweden	221 85
2	ENT-department, Karolinska University Hospital Huddinge (ENT-department B51)	Stockholm		Sweden	141 86