Research clinical trials of Grazax , oral
grass pollen vaccine
Specific Immunotherapy with High Dose SQ Standardised
Grass Allergen Tablets was Safe and Well Tolerated
M. Calderon, Upper Respiratory Medicine, Royal Brompton Hospital,
Imperial College, London, United Kingdom, M. Essendrop, Group
Clinical Development, ALK-Abelló A/S, Hørsholm,
Denmark.. Specific Immunotherapy with High Dose SQ Standardised
Grass Allergen Tablets was Safe and Well Tolerated. Journal
of Investigational Allergology and Clinical Immunology 2006;.
Abstract: Background: Sublingual immunotherapy with grass
allergen tablets may be the future treatment for grass pollen
allergy because it reduces symptoms and medication use, improves
quality of life and is easy to use. Rhinoconjunctivitis and
asthma co-exist and we aimed to find a safe dose range of
a self-administered grass allergen tablet (GRAZAX®) in
patients suffering from rhinoconjunctivitis and asthma. Methods:
4 doses were investigated in a randomised, double-blind, placebo-controlled,
dose escalation trial. Outside the pollen season 4 groups
of 12 patients commenced treatment in a staggered manner,
at intervals of 1 week. For 28 days doses of 75 000 (approximately
15µg Phleum pratense protein 5), 150 000, 300 000, 500
000 standardised quality tablet (SQ-T) units or placebo were
given once daily as sublingual tablets. Results: Fortythree
patients were randomised to receive either active treatment
or placebo (3:1). Each dose group consisted of 12 patients
except the 500 000 SQ-T group (5 active, 2 placebo). No asthma
exacerbations were seen and no serious or severe adverse events
were reported. The majority of adverse events were local reactions.
The number of adverse events was dose related. No patients
withdrew from the study. Conclusions: Treatment with grass
allergen tablets in doses up to 500 000 SQ-T in patients with
asthma and rhinoconjunctivitis was safe and well tolerated.
Efficacy and safety of sublingual immunotherapy with
grass allergen tablets for seasonal allergic rhinoconjunctivitis
Ronald Dahl, MD, the Department of Respiratory Diseases, Aarhus
University Hospital; Alexander Kapp, MD, the Department of
Dermatology and Allergology, Hannover Medical University;
Giselda Colombo, MD, Ospedale San Raffaele del Monte Tabor,
Medicina Interna Allergologia, Milan; Jan G. R. de Monchy,
MD, the Division of Allergology, University of Groningen;
Sabina Rak, MD, the Section of Allergy, Sahlgrenska University
Hospital, Gothenburg; Waltraud Emminger, MD, Allergie-Ambulatorium
Rennweg, Vienna; Montserrat Fernandez Rivas, MD, Fundación
Hospital Alcorcón, Madrid; Mette Ribel, MSc, Group
Clinical Development, ALK-Abelló A/S, Hørsholm;
Stephen R. Durham, MD, the Section of Allergy and Clinical
Immunology, National Heart and Lung Institute, Imperial College
and Royal Brompton Hospital, London.. Efficacy and safety
of sublingual immunotherapy with grass allergen tablets for
seasonal allergic rhinoconjunctivitis. Journal of Allergy
and Clinical Immunology 2006; 118:434-440.
Abstract: Background: Allergen immunotherapy (desensitization)
by injection is effective for seasonal allergic rhinitis and
has been shown to induce long-term disease remission. The
sublingual route also has potential, although definitive evidence
from large randomized controlled trials has been lacking.
Objective: The aim was to confirm the efficacy of a rapidly
dissolving grass allergen tablet (GRAZAX®, ALK-Abelló,
Hørsholm, Denmark) compared with placebo in patients
with seasonal rhinoconjunctivitis. Methods: A longitudinal,
double-blind, placebo-controlled, parallel-group study that
included 51 centers from 8 countries. Subjects were randomized
(1:1) to receive GRAZAX® or placebo once daily. A total
of 634 subjects with a history of grass pollen–induced
rhinoconjunctivitis for at least 2 years and confirmation
of IgE sensitivity (positive skin prick test and serum-specific
IgE) were included in the study. Subjects commenced treatment
at least 16 weeks before the grass pollen season, and treatment
was continued throughout the entire season. Results: The primary
efficacy analysis showed a reduction of 30% in rhinoconjunctivitis
symptom score (P < .0001) and a reduction of 38% in rhinoconjunctivitis
medication score (P < .0001) compared with placebo. Side
effects mainly comprised mild itching and swelling in the
mouth that was in general well tolerated and led to treatment
withdrawal in less than 4% of participants. There were no
serious local side effects and no severe systemic adverse
events. Conclusion: Sublingual immunotherapy with GRAZAX®
was effective in grass pollen–induced rhinoconjunctivitis.
The tablet was well tolerated with minor local side effects.
Clinical implications: GRAZAX® represents a safe alternative
to injection immunotherapy suitable for home use.
Safety and Immunological Changes During Sublingual
Immunotherapy
HJ Malling, Allergy Clinic, National University Hospital,
Copenhagen, Denmark; L Lund, ALK-Abelló A/S, Hørsholm,
Denmark; H Ipsen, ALK-Abelló A/S, Hørsholm,
Denmark; L Poulsen, Allergy Clinic, National University Hospital,
Copenhagen, Denmark.. Safety and Immunological Changes During
Sublingual Immunotherapy. Journal of Investigational Allergology
and Clinical Immunology 2006; 16(3):162-168.
Abstract: Immunotherapy is the only treatment for allergy
that has the potential to alter the natural course of the
disease. Sublingual immunotherapy for grass pollen-induced
rhinoconjunctivitis has been developed to make immunotherapy
available to a broader group of allergic patients. Here, a
safe dose range and the safety during daily sublingual administration
were investigated for a new tablet-based sublingual immunotherapy
for grass pollen allergy. Simultaneously, immunological changes
were monitored. A randomized, double-blind, placebo-controlled
phase I trial was undertaken, with stepwise dose-escalation
during the dose-finding period, and afterwards with daily
dosing 8 weeks prior to and 15 weeks during the grass pollen
season (2500, 25 000, or 75 000 standardized quality tablet
[SQ-T] units, or placebo). Fifty-two participants with grass
pollen-induced rhinoconjunctivitis and a positive skin prick
test and specific IgE to Phleum pratense entered the trial.
During the daily-dose treatment periods, 67% of the participants
reported adverse events. The most frequent were itching in
the mouth, eyes, or throat, and rhinitis, and most were mild
and resolved within 1 day. Two participants withdrew due to
adverse events (sting and blisters in the mouth and itching
in the mouth). Time- and dosedependent increases of Phleum
pratense-specific IgG, IgA, IgE, and IgE-competing components
were found in serum during the first 8 weeks of daily dosing,
indicating that the treatment had a significant allergen-specific
effect on the immune system. In conclusion, the grass allergen
tablet, administered in a dose of 75 000 SQ-T once daily,
was well tolerated and displayed systemic immunogenicity.
Sublingual immunotherapy with once-daily grass allergen tablets
A randomized controlled trial in seasonal allergic rhinoconjunctivitis
print
Stephen R. Durham, MD, The Royal Brompton and Harefield Hospitals
National Health Service Trust and Imperial College, National
Heart and Lung Institute, London; William H. Yang, MD, The
Allergy and Asthma Research Centre, Ottawa; Martin R. Pedersen,
MSc-Pharm, ALK-Abello´ A/S, Hørsholm, Denmark;
Niels Johansen, MS c-Chem Eng ALK-Abello´ A/S, Hørsholm,
Denmark; Sabina Rak, MD, The Section of Allergy, Sahlgrenska
University Hospital, Göteborg.. Sublingual immunotherapy
with once-daily grass allergen tablets A randomized controlled
trial in seasonal allergic rhinoconjunctivitis. The Journal
of Allergy and Clinical Immunology 2006; 117:802-809.
Abstract: Background: Specific immunotherapy is the only
treatment modality that has the potential to alter the natural
course of allergic diseases. Sublingual immunotherapy has
been developed to facilitate access to this form of treatment
and to minimize serious adverse events. Objective: To investigate
the efficacy and safety of sublingual grass allergen tablets
in seasonal allergic rhinoconjunctivitis. Methods: A multinational,
multicenter, randomized, placebo controlled trial conducted
during 2002 and 2003. Fifty-five centers in 8 countries included
855 participants aged 18 to 65 years who gave a history of
grass pollen–induced allergic rhinoconjunctivitis and
had a positive skin prick test and elevated serum allergen-specific
IgE to Phleum pratense. Participants were randomized to 2500,
25,000, or 75,000 SQ-T grass allergen tablets (GRAZAX®
; ALK-Abelló, Hørsholm, Denmark) or placebo
for sublingual administration once daily. Mean duration of
treatment was 18 weeks. Results: Average rhinoconjunctivitis
scores during the season showed moderate reductions of symptoms
(16%) and medication use (28%) for the grass allergen tablet
75,000 SQ-T (P = .0710; P = .0470) compared with placebo.
Significantly better rhinoconjunctivitis quality of life scores
(P = .006) and an increased number of well days (P = .041)
were also observed. Efficacy was increased in the subgroup
of patients who completed the recommended preseasonal treatment
of at least 8 weeks before the grass pollen season (symptoms,
21%, P = .0020; and medication use, 29%, P = .0120). No safety
concerns were observed. Conclusion: This study confirms dose-dependent
efficacy of the grass allergen tablet. Although further studies
are required, the greater tolerability of the tablet may permit
immunotherapy to be available to a much broader group of patients
with impaired quality of life caused by grass pollen allergy.
Clinical implications: For patients with grasspollen allergy,
sublingual immunotherapy is well tolerated and can reduce
symptoms and improve quality of life.
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