ILIT vs SLIT: Sublingual Immunotherapy Compared to Intralymphatic Immunotherapy With Concomitant Vitamin D, a Randomised Placebo Controlled Study

Sponsor

Lars Olaf Cardell (Other)

Overall Status

Recruiting

CT.gov ID

NCT06061848

Collaborator

(none)

360

Enrollment

Locations

Arms

106.8

Anticipated Duration (Months)

120

Patients Per Site

1.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A national, multicenter, randmised double blind study with parallell arms. 360 patients with grass induced allergic rhinitis will be open randomised 1:2 to 3 years Grazax sublingual immunotherapy or 3 intralymphatic injections with ALK Alutard Timothy. In a second step, the ILIT group will be double blind randomised 1:1 to an intramuscular injection of Vitamin D Vicotrat or placebo, 4 week before the start of the intralymphatic treatment. The primary outcome measure is daily combined symptoms and medication scores during grass pollen season.

Condition or Disease	Intervention/Treatment	Phase
Allergic Rhinitis Due to Grass Pollen	Drug: SLIT Grazax ALK Nordic 75 000 SQ-T Drug: ILIT + Vitamin D Drug: ILIT + placebo	Phase 2/Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

360 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

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

Primary Purpose:

Treatment

Official Title:

Sublingual Immunotherapy Compared to Intralymphatic Immunotherapy With Concomitant Vitamin D, a Randomised Placebo Controlled Study

Actual Study Start Date :

Feb 1, 2023

Anticipated Primary Completion Date :

Dec 28, 2030

Anticipated Study Completion Date :

Dec 28, 2031

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: SLIT Sublingual immunotherapy timothy pollen 75000 SQ-T 1 daily for 3 years	Drug: SLIT Grazax ALK Nordic 75 000 SQ-T Daily sublingual grass allergen tablets
Active Comparator: ILIT + Vitamin D Intramuscular injection of kolecalciferol 100000 IU followed by intralymphatic immunotherapy with 3 monthly injections of grass pollen allergen 1000 SQ-U.	Drug: ILIT + Vitamin D 1 mL of Vicotrat D3, Heyl Pharma, 100 000 IU/mL, as intramuscular injection. Followed by 0,1 mL of Alutard SQ timothy, ALK Nordic, 10 000 SQ-U/mL as three intralymphatic injections Other Names: Alutard SQ timothy and Vicotrat D3
Active Comparator: ILIT + placebo Intramuscular injection of saline solution followed by intralymphatic immunotherapy with 3 monthly injections of grass pollen allergen 1000 SQ-U.	Drug: ILIT + placebo 1 ml of Sodium chloride solution 9 mg/mL as intramuscular injection followed by 0,1 mL of Alutard SQ timothy, ALK Nordic, 10 000 SQ-U/mL as three intralymphatic injections Other Names: Alutard SQ timothy and Sodium chloride

Arm

Intervention/Treatment

Active Comparator: SLIT

Sublingual immunotherapy timothy pollen 75000 SQ-T 1 daily for 3 years

Drug: SLIT Grazax ALK Nordic 75 000 SQ-T

Daily sublingual grass allergen tablets

Active Comparator: ILIT + Vitamin D

Intramuscular injection of kolecalciferol 100000 IU followed by intralymphatic immunotherapy with 3 monthly injections of grass pollen allergen 1000 SQ-U.

Drug: ILIT + Vitamin D

1 mL of Vicotrat D3, Heyl Pharma, 100 000 IU/mL, as intramuscular injection. Followed by 0,1 mL of Alutard SQ timothy, ALK Nordic, 10 000 SQ-U/mL as three intralymphatic injections

Other Names:

Alutard SQ timothy and Vicotrat D3

Active Comparator: ILIT + placebo

Intramuscular injection of saline solution followed by intralymphatic immunotherapy with 3 monthly injections of grass pollen allergen 1000 SQ-U.

Drug: ILIT + placebo

1 ml of Sodium chloride solution 9 mg/mL as intramuscular injection followed by 0,1 mL of Alutard SQ timothy, ALK Nordic, 10 000 SQ-U/mL as three intralymphatic injections

Other Names:

Alutard SQ timothy and Sodium chloride

Outcome Measures

Primary Outcome Measures

CSMS [60-75 days at the grass pollen season year 1; 4 months before treatment. 60-75 days year 2; 6 months after start of treatment.]
Daily Combined Symptoms and Medication Scores (0-3)

Secondary Outcome Measures

CSMS peak pollen season [15 days at the grass pollen season year 1; 4 months before treatment. 15 days year 2; 6 months after start of treatment.]
Daily Combined Symptoms and Medication Scores (0-3) during the 15 consecutive days with the highest pollen count
RQLQ [60-75 days at the grass pollen season year 1; 4 months before treatment. 60-75 days year 2; 6 months after start of treatment.]
Juniper Rhinoconjunctivitis Quality of Life Questionnaire, weekly scores (0-28)
VAS (0-10) [4-6 months before treatment and 6-9 months after treatment]
Recalled symptoms severity at visual analogue scale
Serolology with immunoglobulins [1 year before treatment, 4-6 weeks after treatment, 1 year after treatment]
Total and grass specific levels of IgE, IgG, IgG4, IgA in serum

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

moderate to severe allergic rhinitis due to grass pollen, with Rhinitis Total Symptom Score >/= 8.
informed consent

Exclusion Criteria:

chronic rhinosinusitis
Previous immunotherapy
BMI > 35
house dust mite allergy with symptoms or allergy towards furry animals with exposition
25(OH)Vitamin D levels < 25 or > 75 nmol/L
uncontrolled asthma
severe atopic dermatitis
pregnancy or nursing
autoimmune disease
hyper IgE-syndrome
cardiovascular disease
lung disease
liver or kidney disease
hematologic disorder
metabolic disease
chronic infectious disese
medications interacting with the immune system
cancer
previous cytostatic therapy
medication with beta-blockers or ACE-inhibiters, if medication cannot be paused at the day for treatment
medication with antiepileptic drugs, glykosides, orlistat, statines, thiazide diuretics
Mb Paget, osteoporosis or sarcidosis
Hyperparathyroidism or other disease conferring risk of hypercalcemia
malabsorption or bowel disease with diarrea
tendency for formation of kidney stones
hereditary pseudohypoparathyroidism with decreased phosphorous secretion
use of Vitamin D supplementation or excessive use of sun tanning booths
drug abuse
intake of other study product within 1 month or 6 half times, which ever is longest, before visit 1
Mental incapacity to follow study protocol
withdrawn consent
other significant disease
allergy towards study medication

Contacts and Locations

Locations

	Site	City	Country
1	Skåne University Hospital, ENT department	Lund	Sweden
2	Karolinska University Hospital, ENT-department	Stockholm	Sweden
3	Örebro University Hospital	Örebro	Sweden

Sponsors and Collaborators

Lars Olaf Cardell

Investigators

Principal Investigator: Lars O Cardell, Professor, Karolinska Institutet

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Lars Olaf Cardell, Professor, Karolinska Institutet

ClinicalTrials.gov Identifier:

NCT06061848

Other Study ID Numbers:

Dnr KS: K2021-5840

First Posted:

Sep 29, 2023

Last Update Posted:

Sep 29, 2023

Last Verified:

Sep 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Additional relevant MeSH terms:

Rhinitis

Rhinitis, Allergic

Vitamin D

Study Results

No Results Posted as of Sep 29, 2023