Clinical trial NCT02679105: Intralymphatic Immunotherapy in Increasing Doses, After Subcutaneous Immunotherapy
Official title: Intralymphatic Immunotherapy in Increasing Doses up to 10 000 SQ-U -a Human Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Rhinitis, Allergic
Lead sponsor: Karolinska Institutet
Sponsor class: OTHER
Collaborators: name: Karolinska University Hospital
name: Skane University Hospital
name: Sodra Alvsborgs Hospital
First posted: 2016-02-10
Enrollment: 38
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 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.

Detailed 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.

Eligibility criteria: 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 β-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

Primary outcomes:
measure: Total daily symptoms and medications score
timeFrame: 5-7 months after treatment
Secondary outcomes:
measure: Improvement on Visual Analogue Scale (VAS)
timeFrame: During pollen season and recalled after pollen season, approximately 1 year after the start of treatment.
measure: Change in skin prick test reactivity
timeFrame: 4-8 weeks after treatment, 9-12 months after treatment
measure: Change in symptoms score after nasal allergen challenge
timeFrame: 4-8 weeks after treatment, 9-12 months after treatment
measure: Difference between active and placebo group in Quality of Life measured with Juniper Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)
timeFrame: Up to 7 months after treatment.
measure: Difference between active and placebo group in Quality of Life measured with Sino Nasal Outcome Test -22 (SNOT-22)
timeFrame: Up to 7 months after treatment.
measure: Change in allergen specific S- antibody levels.
timeFrame: 4-8 weeks after treatment, 9-12 months after treatment
measure: Incidence of adverse events graded as mild-moderate-severe
timeFrame: From first injection to 30 days after last injection.
Other outcomes:
Locations:
city: Borås
country: Sweden
facility: Allergy Unit, Södra Älvsborgs Hospital
city: Malmö
country: Sweden
facility: ENT department, Skånes University Hospital Malmö and Lund
city: Stockholm
country: Sweden
facility: ENT department, Karolinska University Hospital
Study officials:
affiliation: Karolinska University Hospital
name: Lars Olaf Cardell, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Senti G, Prinz Vavricka BM, Erdmann I, Diaz MI, Markus R, McCormack SJ, Simard JJ, Wuthrich B, Crameri R, Graf N, Johansen P, Kundig TM. Intralymphatic allergen administration renders specific immunotherapy faster and safer: a randomized controlled trial. Proc Natl Acad Sci U S A. 2008 Nov 18;105(46):17908-12. doi: 10.1073/pnas.0803725105. Epub 2008 Nov 10.
citation: 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.jaci.2012.10.056.
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. No abstract available.
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.