Rhinitis, AllergicPhase 2/3NCT02679105
Intralymphatic Immunotherapy in Increasing Doses, After Subcutaneous Immunotherapy
A Phase 2/3 study testing ALK Alutard birch or 5-grasses and ALK diluent in people with Rhinitis, Allergic, run by Karolinska Institutet at 3 sites in Sweden.
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. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Rhinitis, Allergic
- What is being tested?
- ALK Alutard birch or 5-grasses and ALK diluent
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 38 participants
- Where
- 3 sitesSweden
- Study dates
- May 2015to Mar 2019
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 25Show fewer
- 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
Trial locations and contacts
3 sites in 1 country.
Sweden3 sites
Allergy Unit, Södra Älvsborgs Hospital
Borås, 501 82
ENT department, Skånes University Hospital Malmö and Lund
Malmö, 205 02
ENT department, Karolinska University Hospital
Stockholm, 141 86
About this study
Official title: Intralymphatic Immunotherapy in Increasing Doses up to 10 000 SQ-U -a Human Randomized Clinical Trial
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.
Read the 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.
- Conditions
- Rhinitis, Allergic
- Being tested
- ALK Alutard birch or 5-grasses, ALK diluent
- Medical subject headings
- Rhinitis, Allergic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ALK Alutard birch or 5-grassesDrug
Also called ALK Alutard birch pollen or ALK Alutard grass pollen, ATC-code V01AA, V04CL and V07AB
3 injections with 4-5 weeks interval.
ALK diluentDrug
Also called Human albumin
0,3% human albumin
| Study group | Role | What they receive |
|---|---|---|
| ALK diluent | Placebo comparator | Human albumin Receives: Drug: ALK diluent |
| ALK Alutard birch or 5-grasses | Active comparator | Grass pollen suspension or birch pollen suspension Receives: Drug: ALK Alutard birch or 5-grasses |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total daily symptoms and medications score
Difference between active and placebo group in total daily symptoms and medications score during the pollen season.
Measured: 5-7 months after treatment
Secondary outcomes (7)
Improvement on Visual Analogue Scale (VAS)
Difference in improvement on VAS between active and placebo group.
Measured: During pollen season and recalled after pollen season, approximately 1 year after the start of treatment.
Change in skin prick test reactivity
Tested with ALK Soluprick. Measured as the wheal area in millimeter for birch- or grass pollen.
Measured: 4-8 weeks after treatment, 9-12 months after treatment
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.
Measured: 4-8 weeks after treatment, 9-12 months after treatment
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.
Measured: Up to 7 months 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.
Measured: Up to 7 months after treatment.
Change in allergen specific S- antibody levels.
IgE, IgG, IgG4
Measured: 4-8 weeks after treatment, 9-12 months after treatment
Incidence of adverse events graded as mild-moderate-severe
Measured: From first injection to 30 days after last injection.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2016 (estimated)
- Study startMay 2015
- Primary completionOct 2016
- Study completionMar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Rhinitis, AllergicStudies of the same condition, open and under way.
- More trials run by Karolinska InstitutetThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Karolinska Institutet
- Sponsor type
- University, hospital or other
- Collaborators
- Karolinska University Hospital, Skane University Hospital, Sodra Alvsborgs Hospital
- Responsible party
- Principal investigator, Lars Olaf Cardell, Karolinska Institutet
- Investigators
- Lars Olaf Cardell, Professor, Principal investigator, Karolinska University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02679105
- Sponsor's protocol ID
- 2015-001259-63
- Other IDs
- 2015
- Status last verified
- Sep 2019
- First submitted
- 23 Jan 2016
- Last updated
- 4 Sep 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes
Publications
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.
PubMed 19001265Hylander 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.
PubMed 23374268Witten 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.
PubMed 24035151Hellkvist 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.
PubMed 34379802
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intralymphatic Immunotherapy in Increasing Doses up to 10 000 SQ-U -a Human Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT02679105
- Acronym / sponsor ID
- 2015-001259-63
- Conditions
- Rhinitis, Allergic
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Karolinska InstitutetUniversity, hospital or other
- Collaborators
- Karolinska University Hospital, Skane University Hospital, Sodra Alvsborgs Hospital
- Study start
- May 2015
- Primary completion
- Oct 2016 (actual)
- Study completion
- Mar 2019 (actual)
- First posted
- 10 Feb 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ALK diluent | Placebo comparator | Drug: ALK diluentHuman albumin |
| ALK Alutard birch or 5-grasses | Active comparator | Drug: ALK Alutard birch or 5-grassesGrass pollen suspension or birch pollen suspension |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (25 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ALK Alutard birch or 5-grassesAlso: ALK Alutard birch pollen or ALK Alutard grass pollen, ATC-code V01AA, V04CL and V07AB3 injections with 4-5 weeks interval. | Drug | ALK Alutard birch or 5-grasses |
| ALK diluentAlso: Human albumin0,3% human albumin | Drug | ALK diluent |
Primary outcome
Total daily symptoms and medications score
Time frame: 5-7 months after treatment
Difference between active and placebo group in total daily symptoms and medications score during the pollen season.
7 secondary outcomes
Improvement on Visual Analogue Scale (VAS)
Time frame: During pollen season and recalled after pollen season, approximately 1 year after the start of treatment.
Change in skin prick test reactivity
Time frame: 4-8 weeks after treatment, 9-12 months after treatment
Change in symptoms score after nasal allergen challenge
Time frame: 4-8 weeks after treatment, 9-12 months after treatment
Difference between active and placebo group in Quality of Life measured with Juniper Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)
Time frame: Up to 7 months after treatment.
Difference between active and placebo group in Quality of Life measured with Sino Nasal Outcome Test -22 (SNOT-22)
Time frame: Up to 7 months after treatment.
Change in allergen specific S- antibody levels.
Time frame: 4-8 weeks after treatment, 9-12 months after treatment
Incidence of adverse events graded as mild-moderate-severe
Time frame: From first injection to 30 days after last injection.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2019.
- Results publication: PubMed 19001265Senti 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 publication: PubMed 23374268Hylander 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 publication: PubMed 24035151Witten 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.
- Derived from this study: PubMed 34379802Hellkvist 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.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lars Olaf Cardell, Professor principal investigator
Karolinska University Hospital
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing ALK Alutard birch or 5-grasses and ALK diluent in people with Rhinitis, Allergic, run by Karolinska Institutet at 3 sites in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total daily symptoms and medications score (time frame: 5-7 months after treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02679105, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Sep 2019; AzTrials last refreshed its copy on 2 Nov 2026.