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

Antonio Nieto, Ángel Mazón, María Nieto, Ethel Ibáñez, Dah-Tay Jang, Susana Calaforra, Pilar Alba, Carmen Pérez-Francés, Ruth Llusar, Javier Montoro, Antonio de Mateo, Remedios Alamar, David El-Qutob, Javier Fernández, Luis Moral, Teresa Toral, Mónica Antón, Carmen Andreu, Ángel Ferrer, Isabel-María Flores, Neus Cerdá, Sandra Del Pozo, Raquel Caballero, José Luis Subiza, Miguel Casanovas, Antonio Nieto, Ángel Mazón, María Nieto, Ethel Ibáñez, Dah-Tay Jang, Susana Calaforra, Pilar Alba, Carmen Pérez-Francés, Ruth Llusar, Javier Montoro, Antonio de Mateo, Remedios Alamar, David El-Qutob, Javier Fernández, Luis Moral, Teresa Toral, Mónica Antón, Carmen Andreu, Ángel Ferrer, Isabel-María Flores, Neus Cerdá, Sandra Del Pozo, Raquel Caballero, José Luis Subiza, Miguel Casanovas

Abstract

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.

Keywords: allergoid; clinical trial; i; mannan; mmunotherapy; polymerized.

Conflict of interest statement

AN received fees of Astra‐Zeneca, Merck, Novartis. DE‐Q received fees of Chiesi, Sanofi, Stallèrgenes‐Greer, Astra‐Zeneca, Glaxo‐Smith‐kline, Roxall Medicine, and Novartis. AM, MN, EI, DJ, SC, C P‐F, JM, A de M, RA, JF, LM, MA, CA, and AF declare no conflict of interest. RC and SdP are employees of Inmunotek SL. JLS and MC are shareholders of Inmunotek SL.

© 2022 Inmunotek SL. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.

Figures

FIGURE 1
FIGURE 1
Distribution of groups and study schedule
FIGURE 2
FIGURE 2
Consort diagram of the study population. NPT*: number of subjects with data of NPT al baseline (VO) and at the end (V6)

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