Safety and tolerability of a short ragweed sublingual immunotherapy tablet.
BACKGROUND
MK-3641 is a short ragweed sublingual tablet under investigation for immunotherapy of ragweed pollen-induced allergic rhinitis.


OBJECTIVE
To characterize the safety and tolerability of a ragweed sublingual tablet (Merck/ALK-Abelló) in ragweed-allergic adults with or without conjunctivitis.


METHODS
Data from 4 randomized, double-blinded, placebo-controlled trials of MK-3641 (2 28-day and 2 52-week trials) were evaluated. Pooled analyses examined short-term safety over 28 days from all 4 trials and long-term safety from the 52-week trials.


RESULTS
Across all studies, 757, 198, 454, and 1,058 subjects were randomized to placebo or 1.5, 6, or 12 Amb a 1-U of MK-3641, respectively. Treatment-related adverse events were more frequent in the 6- and 12-Amb a 1-U MK-3641 groups than in the placebo group and were primarily local application-site reactions occurring in the first few days of treatment. There was no treatment-associated loss of asthma control or worsening of asthma associated with treatment. No swellings led to airway obstruction or respiratory compromise. No treatment-related anaphylactic shock, life-threatening, or serious treatment-related adverse events were reported for any MK-3641 dose. Of the 1,707 MK-3641-treated subjects, 1 systemic (anaphylactic) reaction was reported (0.06%). The 52-week long-term assessment was generally similar to the safety profile based on the 28-day assessment.


CONCLUSIONS
MK-3641 doses up to and including 12 Amb a 1-U were well tolerated, with no unexpected safety findings. Sublingual immunotherapy risks such as worsening asthma or airway swellings that could cause airway obstruction were not observed. Systemic reactions and use of epinephrine were uncommon. In these studies, after the first dose was administered in a health care setting, self-administration was well tolerated.


BACKGROUND
clinicaltrials.gov Identifiers: NCT01469182, NCT00783198, NCT00770315, and NCT00978029.
Merck & Co, Inc, Whitehouse Station, New Jersey. Electronic address: hendrik.nolte@merck.com.
Hendrik
H
Nolte
Allergy & Asthma Research Institute, Waco, Texas.
Niran
N
Amar
Bernstein Clinical Research Center and Division of Immunology and Allergy, University of Cincinnati, Cincinnati, Ohio.
David I
DI
Bernstein
North Texas Institute for Clinical Trials, Fort Worth, Texas.
Bobby Q
BQ
Lanier
Creticos Research Group and Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Peter
P
Creticos
Minneapolis Allergy & Asthma Specialists, Minneapolis, Minnesota.
Gary
G
Berman
Merck & Co, Inc, Whitehouse Station, New Jersey.
Amarjot
A
Kaur
Centre de Recherche Appliquée en Allergie de Québec, Québec, Québec, Canada.
Jacques
J
Hébert
Merck & Co, Inc, Whitehouse Station, New Jersey.
Jennifer
J
Maloney
D000286:Administration, Sublingual; D000328:Adult; D000485:Allergens / Q000008:administration & dosage*; D052179:Antigens, Plant / Q000008:administration & dosage*; D054316:Biomarkers, Pharmacological / Q000032:analysis; D003233:Conjunctivitis, Allergic / Q000150:complications / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010936:Plant Extracts / Q000008:administration & dosage*; D006255:Rhinitis, Allergic, Seasonal / Q000150:complications / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D063729:Sublingual Immunotherapy / Q000379:methods*; D013607:Tablets
D000485:Allergens; D052179:Antigens, Plant; D054316:Biomarkers, Pharmacological; D010936:Plant Extracts; D013607:Tablets; C433085:ragweed pollen