Safety and Efficacy Study of Intralymphatic Allergen-specific Immunotherapy

NCT ID: NCT02423707

Last Updated: 2018-08-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 110 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-08-31
• Study Completion Date: 2017-12-31

Brief Summary

Allergen-specific immunotherapy (ASIT) is commonly used to treat patients with allergic rhino-conjunctivitis and asthma, and it is the only proven treatment that affects the long-term development of allergic rhinitis and asthma. The current treatment regime of ASIT requires numerous subcutaneous allergen injections and takes several years to complete. Hence, there is a need to develop more convenient protocols for induction of allergen tolerance.

Emerging evidence suggest that by targeting of antigen presenting cells within the lymph nodes the immunogenicity of the allergen can be enhanced and the number of injections can be reduced.

The purpose of this study is to evaluate whether intralymphatic administration of ASIT is a safe and effective treatment for patients with pollen-induced allergic rhinitis. The long term goal is to provide a base for a more efficient administration of ASIT, which will reduce both the dose necessary and the number of clinic visits associated with the conventional subcutaneous ASIT.

The investigators will make an attempt to reproduce the results of a recent human study of intralymphatic ASIT (clinicaltrials.gov; NCT00470457) in a Swedish clinical setting.

The first part of the study is completed and published (PMID: 23374268)

Detailed Description

In the first part of the study safety and clinical efficacy of ALK Alutard Birch or 5-grass have been evaluated in a RCT with 50 patients. Active patients recieve 3 injections with 1000 SQ-U ALK Alutard or 5-grasses in a lymph node in the groin. Dose interval 4 weeks. This part of the study is completed and published (PMID: 23374268)

In the second part of the study 60 patients participates in a RCT with intralymphatic injections with both ALK Alutard Birch AND ALK Alutard 5-grasses. The injections are given intralymphatically with one allergen in each groin with 30 minutes observation between injections. Dose and dose interval are the same as in the first part of the study; the active group recieves 1000 SQ-U ALK Alutard Birch in right groin and 1000 SQ-U 5-grasses in left groin. The injections are given 3 times with 4 weeks interval. Enrollment and treatment is completed and the results will be evaluated in the autumn 2015.

Conditions

Allergic Rhinitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

ALK Alutard Birch and/or 5-grasses

3 intralymphatic injections with dose 1000 SQ-U and dose interval 4 weeks.

Group Type: ACTIVE_COMPARATOR

ALK Alutard Birch and/or 5-grasses

Intervention Type: DRUG

3 intralymphatic injections of 1000 SQ-U birch and/or grass allergen with 4 weeks interval.

The substance used for the three intralymphatic injections is ALK-alutard SQ Betula verrucosa® and ALK-alutard SQ 5-grasses ® under ATC-code V01AA, V04CL and V07AB which is a depot formulation for subcutaneous use.

ALK diluent

3 intralymphatic injections with dose interval 4 weeks.

Group Type: PLACEBO_COMPARATOR

ALK Diluent

Intervention Type: DRUG

This placebo group will receive 3 injections of 0.3% human albumin instead of active substance

Interventions

ALK Alutard Birch and/or 5-grasses

3 intralymphatic injections of 1000 SQ-U birch and/or grass allergen with 4 weeks interval.

The substance used for the three intralymphatic injections is ALK-alutard SQ Betula verrucosa® and ALK-alutard SQ 5-grasses ® under ATC-code V01AA, V04CL and V07AB which is a depot formulation for subcutaneous use.

Intervention Type: DRUG

ALK Diluent

This placebo group will receive 3 injections of 0.3% human albumin instead of active substance

Intervention Type: DRUG

Other Intervention Names

ALK Alutard Betula Verrucosa and ALK Alutard 5-grasses; Human albumin

Eligibility Criteria

Inclusion Criteria

• Age 18-50,
• Seasonal allergic symptoms for birch and/or grass verified by skin prick test,
• Accepted informed consent

Exclusion Criteria

• Pregnancy or nursing
• Autoimmune or collagen disease (known)
• Cardiovascular disease
• Perennial pulmonary disease
• Hepatic disease
• Renal disease
• Cancer
• Any medication with a possible side-effect of interfering with the immune response
• Previous immuno- or chemotherapy
• Chronic diseases
• Other upper airway disease (non-allergic sinusitis, nasal polyps, chronic obstructive and restrictive lung disease)
• 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
• Alcohol or drug abuse
• Mental incapability of coping with the study
• Withdrawal of informed consent

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Skane University Hospital

OTHER

Sponsor Role: collaborator

Karolinska University Hospital

OTHER

Sponsor Role: collaborator

Karolinska Institutet

OTHER

Sponsor Role: lead

Responsible Party

Lars Olaf Cardell

Professor, Head of Division, MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lars-Olaf Cardell, Prof

Role: PRINCIPAL_INVESTIGATOR

Karolinska Institutet

Locations

Allergic Unit at the Department of Oto-Rhino-Laryngology at Skåne University Hospital Malmö

Malmo, , Sweden

Countries

Sweden

References

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.

Reference Type: BACKGROUND

PMID: 19001265 (View on PubMed)

Other Identifiers

2009-016815-39

Identifier Type: -

Identifier Source: org_study_id