Intralymphatic Immunotherapy in Increasing Doses, After Subcutaneous Immunotherapy

Rhinitis, Allergic Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02679105
• Other study ID #: 2015-001259-63
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: May 2015
• Est. completion date: March 2019

Study information

• Verified date: September 2019
• Source: Karolinska Institutet
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study evaluates the safety and effect of intralymphatic allergen specific immunotherapy in increasing doses. Patients that have already undergone subcutaneous immunotherapy will be treated with three intralymphatic injections in increasing doses; 1000 SQ-U, 3000 SQ-U and 10 000 SQ-U, or placebo.

Description:

38 patients with seasonal allergic rhinitis that have recently (within 20 months) ended a full subcutaneous immunotherapy protocol with birch or grass allergen with improvement but not full symptom relief are recruited. Study subjects are randomized to intralymphatic injections with placebo or ALK Alutard 5-grasses or birch.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 38
• Est. completion date: March 2019
• Est. primary completion date: October 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Age 18-55

• Accepted and signed informed consent.

• Recently (within 20 months) ended a full 3 year program with subcutaneous immunotherapy (SCIT) with amelioration of symptoms but not full symptom relief.

Exclusion Criteria:

• Previously subcutaneous immunotherapy (SCIT) with total symptom relief.

• Previously SCIT but no symptom improvement at all.

• Sensitizations to house dust mite or furry animals, with symptoms.

• Severe atopic dermatitis.

• Patients with significant diseases other than allergic rhinitis. A significant disease is defined as a disease which in the opinion of the investigator may either put the patient at risk because of participation in the study or a disease which may influence the results of the study or the patient's ability to participate in the study.

• Patients with a respiratory tract infection in the past 4 weeks prior to Visit 2.

• Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception (i.e., oral contraceptives, intrauterine devices, diaphragm, or subdermal implants).

• Known autoimmune or collagen disease

• Cardiovascular disease

• Perennial pulmonary disease including asthma

• Hepatic disease

• Known renal insufficiency

• Cancer

• Hematologic disease

• Chronic infectious disease

• Any medication with a possible side-effect of interfering with the immune response

• Previous immuno- or chemotherapy, apart from SCIT

• Disease or conditions rendering the treatment of anaphylactic reactions difficult (symptomatic coronary heart diseases, severe arterial hypertension and treatment with ß-blockers)

• Major metabolic disease

• Known or suspected allergy to the study product

• Obesity with BMI > 30 since subcutaneous fat makes ultrasound imaging of lymph nodes harder which may risk the correct placement of injection.

• Patients who, in the opinion of the investigator, abuse alcohol or drugs within 2 years prior to Visit 1.

• Patients who have taken an investigational drug within 1 month or six half lives, whichever is greater, prior to Visit 1.

• Mental incapability of coping with the study

• Withdrawal of informed consent

Related Conditions & MeSH terms

• Rhinitis
• Rhinitis, Allergic

Intervention

Drug:
• ALK Alutard birch or 5-grasses
3 injections with 4-5 weeks interval.
• ALK diluent
0,3% human albumin

Locations

Country	Name	City	State
Sweden	Allergy Unit, Södra Älvsborgs Hospital	Borås
Sweden	ENT department, Skånes University Hospital Malmö and Lund	Malmö
Sweden	ENT department, Karolinska University Hospital	Stockholm

Sponsors (4)

Lead Sponsor	Collaborator
Karolinska Institutet	Karolinska University Hospital, Skane University Hospital, Sodra Alvsborgs Hospital

Country where clinical trial is conducted

Sweden, 

References & Publications (3)

Hylander T, Latif L, Petersson-Westin U, Cardell LO. Intralymphatic allergen-specific immunotherapy: an effective and safe alternative treatment route for pollen-induced allergic rhinitis. J Allergy Clin Immunol. 2013 Feb;131(2):412-20. doi: 10.1016/j.jac — View Citation

Senti G, Prinz Vavricka BM, Erdmann I, Diaz MI, Markus R, McCormack SJ, Simard JJ, Wüthrich B, Crameri R, Graf N, Johansen P, Kündig TM. Intralymphatic allergen administration renders specific immunotherapy faster and safer: a randomized controlled trial. — View Citation

Witten M, Malling HJ, Blom L, Poulsen BC, Poulsen LK. Is intralymphatic immunotherapy ready for clinical use in patients with grass pollen allergy? J Allergy Clin Immunol. 2013 Nov;132(5):1248-1252.e5. doi: 10.1016/j.jaci.2013.07.033. Epub 2013 Sep 13. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total daily symptoms and medications score	Difference between active and placebo group in total daily symptoms and medications score during the pollen season.	5-7 months after treatment
Secondary	Improvement on Visual Analogue Scale (VAS)	Difference in improvement on VAS between active and placebo group.	During pollen season and recalled after pollen season, approximately 1 year after the start of treatment.
Secondary	Change in skin prick test reactivity	Tested with ALK Soluprick. Measured as the wheal area in millimeter for birch- or grass pollen.	4-8 weeks after treatment, 9-12 months after treatment
Secondary	Change in symptoms score after nasal allergen challenge	0,1 ml of ALK Aquagen Birch or Timothy 10 000 SQU/ml is deposited in each nostril and allergy symptoms are recorded.	4-8 weeks after treatment, 9-12 months after treatment
Secondary	Difference between active and placebo group in Quality of Life measured with Juniper Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)	At peak pollen season after treatment.	Up to 7 months after treatment.
Secondary	Difference between active and placebo group in Quality of Life measured with Sino Nasal Outcome Test -22 (SNOT-22)	At peak pollen season after treatment.	Up to 7 months after treatment.
Secondary	Change in allergen specific S- antibody levels.	IgE, IgG, IgG4	4-8 weeks after treatment, 9-12 months after treatment
Secondary	Incidence of adverse events graded as mild-moderate-severe		From first injection to 30 days after last injection.