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A Phase 2 Randomized Controlled Multisite Study Using Omalizumab-Facilitated Rapid Desensitization to Test Continued vs Discontinued Dosing in Multifood Allergic Individuals

Year: 2018
Type: preprint
Study design: Clinical Trial
Abstract: Background – As there is limited data on the sustainability of desensitization of multifood-oral immunotherapy (multifood-OIT), we conducted a multisite multifood-OIT study to compare the efficacy of successful desensitization with sustained dosing vs discontinued dosing after multifood-OIT. Methods – We enrolled 70 participants, aged 5-22 years with multiple food allergies confirmed by double-blind placebo-controlled food challenges (DBPCFCs). In the open-label phase of the study, all participants received omalizumab (weeks 1-16) and multi-OIT (2-5 allergens; weeks 8-30) and eligible participants (on maintenance dose of each allergen by week 28-29) were randomized 1:1:1 to 1g, 300mg, or 0mg arms (blinded, weeks 30-36) and then tested by food challenge at week 36. Success was defined as passing 2g food challenge to at least 2 foods in week 36. Findings – Most participants were able to reach a dose of 2g or higher of each of 2, 3, 4, and 5 food allergens (as applicable to the participant’s food allergens in OIT) in week 36 food challenges. Using an intent-to-treat analysis, we did not find evidence that a 300mg dose was effectively different than a 1g dose in maintaining desensitization, and both together were more effective than OIT discontinuation (0mg dose) (85% vs 55%, P=0·03). Fifty-five percent of the intent-to-treat participants and 69% of per protocol participants randomized to the 0mg arm showed no objective reactivity after 6 weeks of discontinuation. Cross-desensitization was found between cashew/pistachio and walnut/pecan when only one of the foods was part of OIT. No statistically significant safety differences were found between the three arms. Interpretation – These results suggest that sustained desensitization after omalizumab-facilitated multi-OIT best occurs through continued maintenance OIT dosing of either 300mg or 1g of each food allergen as opposed to discontinuation of multi-OIT. Clinical Trial Number: ClinicalTrials.gov number, NCT02626611 Funding Statement: Funding sources include Jeff and MacKenzie Bezos, Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Jeff and MacKenzie Bezos, NIAID AADCRC U19AI104209 (Galli, Nadeau, and Chinthrajah), Myra Reinhard Foundation, FARE Center of Excellence, EAT (End Allergies Together), Trip Advisor Foundation, CHOP-FARE, Children Hospital of Philadelphia’s Food Allergy Fund, The Sunshine Foundation, the Crown Family Philanthropies, and NCATS (NIH) Grant# UL1TR001422 (Pongracic). Declaration of Interests: Dr. Kari Nadeau: NIAID CoFAR, NIAID Immune Tolerance Network, NHLBI Data and Safety Monitoring Board, NIEHS grant awardee, EPA grant awardee, FARE Center of Excellence Director, WAO Center of Excellence Director, site principal investigator (AImmune Phase 3, DBV phase 3, AnaptysBio Phase 1, Astellas Phase 1). Dr. Sharon Chinthrajah receives grant support from CoFAR NIAID, AImmune, DBV Technologies, Astellas, AnaptysBio, and is on the Regional Advisory Board for AImmune. Dr. Julie Wang: NIAID CoFAR, Aimmune, DBV Technologies, UpToDate. Dr. Scott Sicherer: NIAID CoFAR, HAL-Allergy, UpToDate, Johns Hopkins University Press, Board of Directors of the American Academy of Allergy, Asthma and Immunology, and is associate editor of J Allergy Clin Immunol Pract. Dr. Hugh Sampson: NIAID and is the Chief Scientific Officer at DBV Technologies (60%) and a consultant for Allertein Therapeutics, LLC. Dr. Jonathan Spergel receives grant support from DBV Technology, Aimmune and NIH, is a consultant with Regeneron and Shire, and is on the Scientific Advisory Board at DBV Technology. Dr. Whitehorn is a consultant and principal investigator for DBV Technology. Dr. Cianferoni receives funding from DBV Technology. Dr. Stephen J. Galli receives grant support from NIAID, NIAMS, and the Tobacco-Related Disease Research Program (U. California). Dr. Assa’ad is a principal investigator for DBV Technologies, Aimmune Pharmaceuticals, Astellas, and the National Institute of Health. All other authors declare no conflicts of interest. Ethics Approval Statement: The research protocol was approved by the relevant institutional review boards (IRB) or ethics committees under a Food and Drug Administration approved- Investigational New Drug.
Authors: Sandra Andorf, Natasha Purington, Divya Kumar, Andrew Long, Katherine O'Laughlin, Scott H. Sicherer, Hugh A. Sampson, Antonella Cianferoni, Terri Brown Whitehorn, Daniel Petroni, Melanie Makhija, Rachel G. Robison, Michelle B. Lierl, Stephanie Logsdon, Manisha Desai, Stephen J. Galli, Efren L. Rael, Amal Assa’ad, R. Sharon Chinthrajah, Jacqueline A. Pongracic, Jonathan M. Spergel, Jonathan S. Nguyen‐Van‐Tam, Stephen A. Tilles, Julie Wang, Kari C. Nadeau
Institutions: Stanford University, Mount Sinai Health System, Icahn School of Medicine at Mount Sinai, University of Pennsylvania, University of Washington, Lurie Children's Hospital, Cincinnati Children's Hospital Medical Center, University of Southern California
Language: English
Field: Medicine
Open Access status: green
OpenAlex ID: W3211889602
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