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Intralymphatic Immunotherapy in Increasing Doses, After Subcutaneous Immunotherapy

Primary Purpose

Rhinitis, Allergic

Status

Completed

Phase

Phase 2

Locations

Sweden

Study Type

Interventional

Intervention

ALK Alutard birch or 5-grasses

ALK diluent

About this trial

This is an interventional treatment trial for Rhinitis, Allergic

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Allergy Unit, Södra Älvsborgs Hospital
ENT department, Skånes University Hospital Malmö and Lund
ENT department, Karolinska University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

ALK diluent

ALK Alutard birch or 5-grasses

Arm Description

Human albumin

Grass pollen suspension or birch pollen suspension

Outcomes

Primary Outcome Measures

Total daily symptoms and medications score

Difference between active and placebo group in total daily symptoms and medications score during the pollen season.

Secondary Outcome Measures

Improvement on Visual Analogue Scale (VAS)

Difference in improvement on VAS between active and placebo group.

Change in skin prick test reactivity

Tested with ALK Soluprick. Measured as the wheal area in millimeter for birch- or grass pollen.

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.

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.

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.

Change in allergen specific S- antibody levels.

IgE, IgG, IgG4

Incidence of adverse events graded as mild-moderate-severe

Full Information

NCT ID

NCT02679105

First Posted

January 23, 2016

Last Updated

September 3, 2019

Sponsor

Karolinska Institutet

Collaborators

Karolinska University Hospital, Skane University Hospital, Sodra Alvsborgs Hospital

1. Study Identification

Unique Protocol Identification Number

NCT02679105

Brief Title

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

2. Study Status

Record Verification Date

September 2019

Overall Recruitment Status

Completed

Study Start Date

May 2015 (undefined)

Primary Completion Date

October 2016 (Actual)

Study Completion Date

March 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Karolinska Institutet

Collaborators

Karolinska University Hospital, Skane University Hospital, Sodra Alvsborgs Hospital

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Rhinitis, Allergic

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

38 (Actual)

8. Arms, Groups, and Interventions

Arm Title

ALK diluent

Arm Type

Placebo Comparator

Arm Description

Human albumin

Arm Title

ALK Alutard birch or 5-grasses

Arm Type

Active Comparator

Arm Description

Grass pollen suspension or birch pollen suspension

Intervention Type

Drug

Intervention Name(s)

ALK Alutard birch or 5-grasses

Other Intervention Name(s)

ALK Alutard birch pollen or ALK Alutard grass pollen, ATC-code V01AA, V04CL and V07AB

Intervention Description

3 injections with 4-5 weeks interval.

Intervention Type

Drug

Intervention Name(s)

ALK diluent

Other Intervention Name(s)

Human albumin

Intervention Description

0,3% human albumin

Primary Outcome Measure Information:

Title

Total daily symptoms and medications score

Description

Difference between active and placebo group in total daily symptoms and medications score during the pollen season.

Time Frame

5-7 months after treatment

Secondary Outcome Measure Information:

Title

Improvement on Visual Analogue Scale (VAS)

Description

Difference in improvement on VAS between active and placebo group.

Time Frame

During pollen season and recalled after pollen season, approximately 1 year after the start of treatment.

Title

Change in skin prick test reactivity

Description

Tested with ALK Soluprick. Measured as the wheal area in millimeter for birch- or grass pollen.

Time Frame

4-8 weeks after treatment, 9-12 months after treatment

Title

Change in symptoms score after nasal allergen challenge

Description

0,1 ml of ALK Aquagen Birch or Timothy 10 000 SQU/ml is deposited in each nostril and allergy symptoms are recorded.

Time Frame

4-8 weeks after treatment, 9-12 months after treatment

Title

Difference between active and placebo group in Quality of Life measured with Juniper Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)

Description

At peak pollen season after treatment.

Time Frame

Up to 7 months after treatment.

Title

Difference between active and placebo group in Quality of Life measured with Sino Nasal Outcome Test -22 (SNOT-22)

Description

At peak pollen season after treatment.

Time Frame

Up to 7 months after treatment.

Title

Change in allergen specific S- antibody levels.

Description

IgE, IgG, IgG4

Time Frame

4-8 weeks after treatment, 9-12 months after treatment

Title

Incidence of adverse events graded as mild-moderate-severe

Time Frame

From first injection to 30 days after last injection.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Lars Olaf Cardell, Professor

Organizational Affiliation

Karolinska University Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Allergy Unit, Södra Älvsborgs Hospital

City

Borås

ZIP/Postal Code

501 82

Country

Sweden

Facility Name

ENT department, Skånes University Hospital Malmö and Lund

City

Malmö

ZIP/Postal Code

205 02

Country

Sweden

Facility Name

ENT department, Karolinska University Hospital

City

Stockholm

ZIP/Postal Code

141 86

Country

Sweden

12. IPD Sharing Statement

Plan to Share IPD

Yes

Citations:

PubMed Identifier

19001265

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.

Results Reference

result

PubMed Identifier

23374268

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.

Results Reference

result

PubMed Identifier

24035151

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.

Results Reference

result

PubMed Identifier

34379802

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.

Results Reference

derived

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Intralymphatic Immunotherapy in Increasing Doses, After Subcutaneous Immunotherapy

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