Intralymphatic Immunotherapy Enhanced by Vitamin-D, a Randomized Placebo-controlled Trial and Comparison With SLIT (ILIT vs SLIT)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Allergic Rhinitis Due to Grass Pollen
• Intervention / Treatment: Drug: SLIT Grazax ALK Nordic 75 000 SQ-T; Drug: ILIT + Vitamin D; Drug: ILIT + placebo

• Study Type: Interventional
• Enrollment (Estimated): 360
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Agneta Karlsson, Study nurse; Phone Number: +46 72 580 29 63; Email: agneta.j.karlsson@regionstockholm.se
• Study Contact Backup: Name: Laila Hellkvist, MD, PhD; Phone Number: +46 72 469 46 07; Email: laila.hellkvist@regionstockholm.se

Study Locations

• Sweden
  • Lund, Sweden
    • Not yet recruiting
    • Skåne University Hospital, ENT department
    • Contact: Franziska Nordström, MD; Email: franziska.nordstrom@skane.se
  • Stockholm, Sweden
    • Recruiting
    • Karolinska University Hospital, ENT-department
    • Contact: Laila Hellkvist, MD, PhD; Phone Number: +46 72 469 46 07; Email: laila.hellkvist@regionstockholm.se
    • Contact: Eirini Paziou, MD; Phone Number: +46 8 123 723 96; Email: eirini.paziou@regionstockholm.se
  • Örebro, Sweden
    • Not yet recruiting
    • Orebro University Hospital
    • Contact: Amanj Saber, MD; Email: amanj.saber@regionorebrolan.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CSMS	Daily Combined Symptoms and Medication Scores (0-3)	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.

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Lars Olaf Cardell
• Investigators: Principal Investigator: Lars O Cardell, Professor, Karolinska Institutet

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2023
• Primary Completion (Estimated): December 28, 2030
• Study Completion (Estimated): December 28, 2031

Study Registration Dates

• First Submitted: September 11, 2023
• First Submitted That Met QC Criteria: September 25, 2023
• First Posted (Actual): September 29, 2023

Study Record Updates

• Last Update Posted (Actual): November 29, 2023
• Last Update Submitted That Met QC Criteria: November 27, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• 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; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Vitamin D
• Other Study ID Numbers: Dnr KS: K2021-5840

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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