The Safety and Efficacy of Intralymphatic Immunotherapy in Pollen Allergic Adolescents and Young Adults With Asthma

September 25, 2020 updated by: Gunilla Hedlin, Karolinska Institutet

The Safety and Efficacy of Intralymphatic Immunotherapy in Pollen Allergic Adolescents and Young Adults With Asthma: A Randomized Placebo-controlled Trial

The study evaluates the safety and efficacy of intralymphatic allergen-specific immunotherapy given to adolescents and young adults who are allergic to grass or birch pollen and have mild or moderate asthma. Patients will be treated with three intralymphatic injections; 1000 SQ-U x3 with 4-5 weeks interval, or placebo with 4-5 weeks interval. The patients receiving treatment will be given a fourth injection one year after the initial injections. The study is conducted in collaboration between Professor Lars Olof Cardell (ENT), prof Gunilla Hedlin (Pediatrics) and prof Marianne van Hage (Immunology)".

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

30 patients with seasonal allergic rhinitis due to birch or grass pollen are included. Study subjects are randomized to intralymphatic injections with placebo or ALK Alutard 5-grasses / birch or placebo. The patients receiving treatment will be given a fourth injection one year after the initial injections.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

16 years to 50 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Allergic rhinitis due to grass or birch pollen
  • Mild to moderate asthma with a positive methacholine challenge
  • Accepted and signed informed consent.

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 ongoing exposure and 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
  • 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
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Placebo
ALK diluent 0,3% human albumin'
Drug: ALK diluent 0,3% human albumin
Intralymphatic injection with 0.1 ml. 3 injections with 4-5 weeks interval
Other Names:
  • Human albumin
Experimental: Active treatment
Intervention: Drug ALK Alutard birch or 5-grasses. Grass pollen suspension or birch pollen suspension
Drug: ALK Alutard birch or 5-grasses
Intralymphatic injection with 1000 units. 3 injections with 4-5 weeks interval (0,1 ml) and one additional booster injection with 1000 units before the second pollen season.
Other Names:
  • ALK Alutard birch pollen or ALK Alutard grass pollen

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in Symptoms Score After Nasal Allergen Challenge
Time Frame: At inclusion (pre-treatment), 12 months after inclusion (after first pollen season) and for the active treated patients 24 months after inclusion (after the second pollen season).
0,1 ml of ALK Aquagen birch or timothy 10 000 SQU/ml is deposited in each nostril and allergy symptoms are recorded. Symptoms during NPTs were scored according to the Lebel scoring scale. Symtom scores at 5, 15, and 30 minutes after nasal administration of the allergenextract were summed to represent the symptom-score at each nasal challenge (at inclusion, 12 months after inclusion and for the active patients 24 months after inclusion). The scoring system identifies nasal, eye, and ear symptoms: rhinorrhea, nasal pruritus, nasal congestion, ocular pruritus, watery eyes, and itchy ears, each graded on a scale from 0 to 3 points, and a total score was summarized after subtracting the starting score (min score is 0 and maximum score is 54 + the number of sneezes). Higher scores mean worse outcome.
At inclusion (pre-treatment), 12 months after inclusion (after first pollen season) and for the active treated patients 24 months after inclusion (after the second pollen season).

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change on Visual Analogue Scale (VAS
Time Frame: At inclusion (pre-treatment), 12 months after inclusion (after first pollen season) and for the active treated patients 24 months after inclusion (after the second pollen season).
Treatment effect was evaluated by asking the patients to compare their allergic symptoms during the last pollen season with the pollen season before treatment on a visual analogue scale ranging from 0 (unchanged symptoms, no improvement) to 10 (total symptom relief, complete recovery).
At inclusion (pre-treatment), 12 months after inclusion (after first pollen season) and for the active treated patients 24 months after inclusion (after the second pollen season).
Change in Quality of Life
Time Frame: At inclusion (pre-treatment), 12 months after inclusion (after first pollen season) and for the active treated patients 24 months after inclusion (after the second pollen season).
Difference before and after treatment in Quality of Life. Quality of life was assessed using the Juniper Asthma Quality of Life Questionnaire, giving a score ranging from 1 to 7, and a change in score of 0.5 points is considered clinically relevant. Lower value is considered worse outcome.
At inclusion (pre-treatment), 12 months after inclusion (after first pollen season) and for the active treated patients 24 months after inclusion (after the second pollen season).
Change in Allergen-specific Serum Immunoglobulin E (IgE) Levels Compared to Before Treatment
Time Frame: At inclusion (pre-treatment), 12 months after inclusion (after first pollen season) and for the active treated patients 24 months after inclusion (after the second pollen season).
Allergen-specific IgE levels were measured by ImmunoCAP (Thermo Scientific, Uppsala, Sweden) for birch (t3) and timothy grass (g6) pollen according to the manufacturer's instructions. A cutoff level ≥ 0.35 kUA/L was considered positive.
At inclusion (pre-treatment), 12 months after inclusion (after first pollen season) and for the active treated patients 24 months after inclusion (after the second pollen season).
Change in Asthma Symptom Scores
Time Frame: At inclusion (pre-treatment), 12 months after inclusion (after first pollen season) and for the active treated patients 24 months after inclusion (after the second pollen season).
Asthma control 4 weeks before follow-up was estimated with the asthma control test. The score is based on a questionnaire with 5 questions concerning the patients asthma. Each question can be given a score from 1 to 5 points. The answers for each question is added together, where a minimum score of 5 and a maximum score of 25 can be obtained. Higher scores indicate improved outcome and a score of 19 or less suggests poorly controlled asthma.
At inclusion (pre-treatment), 12 months after inclusion (after first pollen season) and for the active treated patients 24 months after inclusion (after the second pollen season).
Change in Pulmonary Function Measurement (Spirometry)
Time Frame: At inclusion (pre-treatment), 12 months after inclusion (after first pollen season) and for the active treated patients 24 months after inclusion (after the second pollen season).
FEV1 were measured according to international guidelines and results presented in % of predicted values according to the patients height, gender, age and weight.
At inclusion (pre-treatment), 12 months after inclusion (after first pollen season) and for the active treated patients 24 months after inclusion (after the second pollen season).
Changes in Airway Inflammation Assessed by Exhaled Nitric Oxide
Time Frame: At inclusion (pre-treatment), 12 months after inclusion (after first pollen season) and for the active treated patients 24 months after inclusion (after the second pollen season).
Nitric oxide in exhaled air, p.p.b. were measured according to international guidelines, and higher values indicate worse outcome.
At inclusion (pre-treatment), 12 months after inclusion (after first pollen season) and for the active treated patients 24 months after inclusion (after the second pollen season).
Change in Symptom and Medication-score
Time Frame: At inclusion (pre-treatment), 12 months after inclusion (after first pollen season) and for the active treated patients 24 months after inclusion (after the second pollen season).
Modified Symptom scores and Medication score were calculated taking into account the frequency: daily (4 points); every second day (3 points); 1 to 3 days per week (2 points); occasionally (1 point); never (0 points), for the following symptoms: blocked nose, rhinorrhea, fatigue, sneezing, and asthma symptoms, and for the following medications used: local and systemic antihistamines, nasal steroids, asthma medication, and eye drops. A minimum score of 0 and a maximum score of 20 points for symptoms and 16 points for medication could be obtained. Higher values indicate worse outcome.
At inclusion (pre-treatment), 12 months after inclusion (after first pollen season) and for the active treated patients 24 months after inclusion (after the second pollen season).
Changes in Response to a Bronchial Challenge With Methacholine
Time Frame: At inclusion (pre-treatment), 12 months after inclusion (after first pollen season) and for the active treated patients 24 months after inclusion (after the second pollen season).
Methacholine challenge to test the bronchial hyperresponsiveness in the airways of the included subjects. The subject will inhale increasing doses of methacholine. Spirometry is performed before and between each inhalation. The cumulative dose of methacholine needed to elicit at 20% decrease in FEV1 (PD20) is reported. Lower values indicate worse outcome.
At inclusion (pre-treatment), 12 months after inclusion (after first pollen season) and for the active treated patients 24 months after inclusion (after the second pollen season).
Change in Allergen-specific Serum Immunoglobulin (Ig) G and Ig4 Levels Compared to Before Treatment
Time Frame: At inclusion (pre-treatment), 12 months after inclusion (after first pollen season) and for the active treated patients 24 months after inclusion (after the second pollen season).
Allergen-specific IgG and IgG4 level was measured by ImmunoCAP (Thermo Scientific, Uppsala, Sweden) for birch (t3) and timothy grass (g6) pollen according to the manufacturer's instructions. A cutoff 2 mg/L for IgG and 0.05 mg/L for IgG4 was considered positive.
At inclusion (pre-treatment), 12 months after inclusion (after first pollen season) and for the active treated patients 24 months after inclusion (after the second pollen season).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Karolinska Institutet

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 6, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 8, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 9, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 28, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 25, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • DNR 2012/701 EPN Lund

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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