ARTEMIS Peanut Allergy In Children

This is a European, multicenter, double-blind, randomized, placebo-controlled 2-arm study of the efficacy and safety of AR101 in peanut-allergic children.

• AR101 powder provided in capsules & sachets (Biological): Study product formulated to contain peanut protein at different dosage strengths for use as defined in the protocol
• Placebo powder provided in capsules & sachets (Other): Study product formulated to contain only inactive ingredients for use as defined in the protocol

Primary outcomes

• The Proportion of Subjects Ages 4-17 Who Tolerated a Single Highest Dose of at Least 1000 mg in the Exit Oral Food Challenge. [Approximately 9 months]: The proportion of subjects in the ITT population who achieve desensitization as determined by tolerating specified challenge doses of peanut protein with no more than mild symptoms at the Exit Oral Food Challenge.

Secondary outcomes

• Proportion of Subjects Ages 4-17 Who Tolerated a Single Highest Dose of at Least 600 mg in the Exit Oral Food Challenge [Approximately 9 months]: The proportion of subjects in the ITT population who achieve desensitization as determined by tolerating specified challenge doses of peanut protein with no more than mild symptoms at the Exit Oral Food Challenge.
• Proportion of Subjects Ages 4-17 Who Tolerated a Single Highest Dose of at Least 300 mg in the Exit Oral Food Challenge. [Approximately 9 months]: The proportion of subjects in the ITT population who achieve desensitization as determined by tolerating specified challenge doses of peanut protein with no more than mild symptoms at the Exit Oral Food Challenge.
• Maximum Severity of Symptoms at Any Challenge Dose During the Peanut Exit Oral Food Challenge [Approximately 9 months]: The maximum severity of symptoms on 4 levels: 0-None, 1-Mild, 2-Moderate, 3-Severe or higher (severe, life threatening, fatal) observed in the DBPCFC at any dose (1000 mg or lower)

Sex: All, ages: 4 Years to 17 Years

Key Inclusion Criteria:

* Age 4 to 17 years, inclusive
* Clinical history of allergy to peanuts
* Serum SPT ≥ 3 mm greater than control and/or psIgE ≥ 0.35 kUa/L
* Dose limiting symptoms after consuming a single dose of peanut protein ≤ 300 mg
* Written informed consent from the subject's parent/guardian
* Written assent from the subject as appropriate (per local regulatory requirements)
* Use of effective birth control by sexually active female subjects of childbearing potential

Key Exclusion Criteria:

* History of cardiovascular disease, including uncontrolled or inadequately controlled hypertension
* History of severe asthma (NHLBI criteria steps 5 or 6), or mild to moderate asthma (2007 NHLBI criteria steps 1-4) that is uncontrolled or difficult to control
* History of severe or life threatening episode of anaphylaxis or anaphylactic shock within 60 days of screening
* History of eosinophilic esophagitis (EoE), other eosinophilic gastrointestinal disease, chronic, recurrent, or severe gastroesophageal reflux disease (GERD), symptoms of dysphagia or recurrent gastrointestinal symptoms of undiagnosed etiology
* History of a mast cell disorder, including mastocytosis, urticaria pigmentosa, chronic idiopathic or chronic physical urticaria beyond simple dermatographism (e.g., cold urticaria, cholinergic urticaria), and hereditary or idiopathic angioedema
* Any other condition that, in the opinion of the Investigator, precludes participation for reasons of safety

Participant flow

Outcome results

• The Proportion of Subjects Ages 4-17 Who Tolerated a Single Highest Dose of at Least 1000 mg in the Exit Oral Food Challenge. (Primary), Count of participants, Participants: AR101 77; Placebo 1 (p <0.0001)
• Proportion of Subjects Ages 4-17 Who Tolerated a Single Highest Dose of at Least 600 mg in the Exit Oral Food Challenge (Secondary), Count of participants, Participants: AR101 90; Placebo 4 (p <0.0001)
• Proportion of Subjects Ages 4-17 Who Tolerated a Single Highest Dose of at Least 300 mg in the Exit Oral Food Challenge. (Secondary), Count of participants, Participants: AR101 97; Placebo 7 (p <0.0001)
• Maximum Severity of Symptoms at Any Challenge Dose During the Peanut Exit Oral Food Challenge (Secondary), Count of participants, Participants: AR101 47; Placebo 0 (p <0.0001)

Adverse events

Time frame: Approximately 9 months

Serious adverse events by term

Other adverse events by term

• Results publication: Blumchen K, Kleinheinz A, Klimek L, Beyer K, Anagnostou A, Vogelberg C, Butovas S, Ryan R, Norval D, Zeitler S, Du Toit G. Post hoc analysis examining symptom severity reduction and symptom absence during food challenges in individuals who underwent oral immunotherapy for peanut allergy: results from three trials. Allergy Asthma Clin Immunol. 2023 Mar 13;19(1):21. doi: 10.1186/s13223-023-00757-8. PMID 36915184
• Results publication: Nilsson C, Scurlock AM, Dellon ES, Brostoff JM, Pham T, Ryan R, Brown KR, Adelman DC, Aceves SS. Onset of eosinophilic esophagitis during a clinical trial program of oral immunotherapy for peanut allergy. J Allergy Clin Immunol Pract. 2021 Dec;9(12):4496-4501. doi: 10.1016/j.jaip.2021.07.048. Epub 2021 Aug 11. No abstract available. PMID 34389504
• Results publication: Fernandez-Rivas M, Vereda A, Vickery BP, Sharma V, Nilsson C, Muraro A, Hourihane JO, DunnGalvin A, du Toit G, Blumchen K, Beyer K, Smith A, Ryan R, Adelman DC, Jones SM. Open-label follow-on study evaluating the efficacy, safety, and quality of life with extended daily oral immunotherapy in children with peanut allergy. Allergy. 2022 Mar;77(3):991-1003. doi: 10.1111/all.15027. Epub 2021 Sep 24. PMID 34320250
• Results publication: O'B Hourihane J, Beyer K, Abbas A, Fernandez-Rivas M, Turner PJ, Blumchen K, Nilsson C, Ibanez MD, Deschildre A, Muraro A, Sharma V, Erlewyn-Lajeunesse M, Zubeldia JM, De Blay F, Sauvage CD, Byrne A, Chapman J, Boralevi F, DunnGalvin A, O'Neill C, Norval D, Vereda A, Skeel B, Adelman DC, du Toit G. Efficacy and safety of oral immunotherapy with AR101 in European children with a peanut allergy (ARTEMIS): a multicentre, double-blind, randomised, placebo-controlled phase 3 trial. Lancet Child Adolesc Health. 2020 Oct;4(10):728-739. doi: 10.1016/S2352-4642(20)30234-0. Epub 2020 Jul 20. PMID 32702315

• Study Protocol (PDF, 2018-08-28)
• Statistical Analysis Plan (PDF, 2018-12-04)

• Director of Regulatory Affairs, Study director, Aimmune Therapeutics