First‐in‐human phase 2 trial with mite allergoids coupled to mannan in subcutaneous and sublingual immunotherapy

• Published in: Allergy (Copenhagen) Vol. 77; no. 10; pp. 3096 - 3107
• Main Authors: Nieto, Antonio, Mazón, Ángel, Nieto, María, Ibáñez, Ethel, Jang, Dah‐Tay, Calaforra, Susana, Alba, Pilar, Pérez‐Francés, Carmen, Llusar, Ruth, Montoro, Javier, Mateo, Antonio, Alamar, Remedios, El‐Qutob, David, Fernández, Javier, Moral, Luis, Toral, Teresa, Antón, Mónica, Andreu, Carmen, Ferrer, Ángel, Flores, Isabel‐María, Cerdá, Neus, Pozo, Sandra, Caballero, Raquel, Subiza, José Luis, Casanovas, Miguel
• Format: Journal Article
• Language: English
• Published: Denmark Blackwell Publishing Ltd 01.10.2022; John Wiley and Sons Inc
• Subjects: Allergens; allergoid; Allergoids; Animals; Antigens, Dermatophagoides; clinical trial; Dendritic cells; Dermatophagoides pteronyssinus; Double-Blind Method; Humans; Immunotherapy; Lymphocytes T; Mannan; Mannans; mmunotherapy; Oral administration; Original; ORIGINAL ARTICLES; Parasites; Placebos; polymerized; Provocation tests; Pyroglyphidae; Sublingual Immunotherapy - adverse effects; Treatment Outcome; Vaccines; clinical trial; i; polymerized; mannan; mmunotherapy; allergoid
• ISSN: 0105-4538; 1398-9995; 1398-9995
• DOI: 10.1111/all.15374

Background Polymerized allergens conjugated to non‐oxidized mannan (PM‐allergoids) are novel vaccines targeting dendritic cells (DCs). Previous experimental data indicate that PM‐allergoids are readily taken up by DCs and induce Treg cells. This first‐in‐human study was aimed to evaluate safety and to find the optimal dose of house dust mite PM‐allergoid (PM‐HDM) administered subcutaneously (SC) or sublingually (SL). Methods In a randomized, double‐blind, double‐dummy, placebo‐controlled trial, 196 subjects received placebo or PM‐HDM at 500, 1000, 3000, or 5000 mannan‐conjugated therapeutic units (mTU)/mL in 9‐arm groups for 4 months. All subjects received 5 SC doses (0.5 ml each) every 30 days plus 0.2 ml SL daily. The primary efficacy outcome was the improvement of titrated nasal provocation tests (NPT) with D. pteronyssinus at baseline and at the end of the study. All adverse events and reactions were recorded and assessed. Secondary outcomes were the combination of symptom and medication scores (CSMS) and serological markers. Results No moderate or severe adverse reactions were reported. Subjects improving the NPT after treatment ranged from 45% to 62% in active SC, 44% to 61% in active SL and 16% in placebo groups. Statistical differences between placebo and active groups were all significant above 500 mTU, being the highest with 3000 mTU SL (p = 0.004) and 5000 mTU SC (p = 0.011). CSMS improvement over placebo reached 70% (p < 0.001) in active 3000 mTU SC and 40% (p = 0.015) in 5000 mTU SL groups. Conclusions PM‐HDM immunotherapy was safe and successful in achieving primary and secondary clinical outcomes in SC and SL at either 3000 or 5000 mTU/ml. This first‐in‐human study evaluates safety and optimal dose of PM‐HDM in SCIT and SLIT. PM‐HDM is safe and shows dose‐dependent clinical efficacy outcomes in SCIT and SLIT. A dose‐response in specific IgG4 to HDM is observed in SCIT, but not SLIT.Abbreviations: AIT, allergy immunotherapy; PM‐HDM, polymerized house dust mite allergoids conjugated with mannan; SCIT, subcutaneous immunotherapy; SLIT, sublingual immunotherapy