E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Allergy to peanuts or peanut-containing foods |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10034202 |
E.1.2 | Term | Peanut allergy |
E.1.2 | System Organ Class | 100000004870 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Efficacy of AR101 treatment in peanut-allergic subjects aged 1 to < 4 years, assessed by tolerability of specified single doses of peanut protein in a double-blind, placebo-controlled food challenge (DBPCFC) |
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E.2.2 | Secondary objectives of the trial |
• Safety and tolerability of study treatment • Efficacy of AR101, assessed by tolerability of other specified single doses of peanut protein in a DBPCFC • Maximum severity of allergy symptoms in a DBPCFC |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Each subject eligible to participate in this study must meet all the following criteria: 1. Aged 1 to < 4 years at randomization. 2. Written informed consent from the legal guardian/parent (or both parents where required by local authorities). Provide assent where required and as appropriate per local requirements. 3. Sensitivity to peanut, defined as one of the following: a. No known history of peanut ingestion and has serum IgE to peanut ≥ 5 kUA/L within 12 months before randomization. b. Documented history of physician-diagnosed IgE-mediated peanut allergy that includes the onset of characteristic* signs and symptoms of allergy within 2 hours of known oral exposure to peanut or peanut-containing food, and has a mean wheal diameter on skin prick test (SPT) to peanut of at least 3 mm greater than the negative control (diluent) or serum IgE to peanut ≥ 0.35 kUA/L, obtained within 12 months before randomization. *Characteristic signs and symptoms of IgE-mediated allergic reactions are generally objective and affect the target organs of skin, GI tract, upper/lower respiratory tract, cardiovascular system, or a combination of target organs as follows: System: Examples of Symptoms (Sampson, 2014) Cutaneous: Pruritus, erythema/flushing, urticaria, angioedema, contact urticaria Ocular: Pruritus, tearing, conjunctival injection, periorbital edema Upper respiratory tract: Pruritus, nasal congestion, rhinorrhea, sneezing, hoarseness, laryngeal edema Lower respiratory tract: Cough, wheezing, dyspnea, chest tightness/pain Gastrointestinal: Oral pruritus, oral angioedema (lips, tongue, or palate), colicky abdominal pain, nausea, emesis, diarrhea Cardiovascular: Tachycardia, dizziness, hypotension, loss of consciousness/ fainting 4. Development of age-appropriate dose-limiting allergy symptoms after consuming single doses of peanut protein > 3 mg to ≤ 300 mg in a screening DBPCFC. 5. A palatable vehicle food to which the subject is not allergic must be available for administering study product. |
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E.4 | Principal exclusion criteria |
Each subject eligible to participate in this study must NOT meet any of the following exclusion criteria: 1. History of severe or life-threatening anaphylaxis anytime before the screening DBPCFC. 2. History of hemodynamically significant cardiovascular or renovascular disease, including uncontrolled or inadequately controlled hypertension. 3. History of biopsy-confirmed diagnosis of EoE; other eosinophilic GI disease; chronic, recurrent, or severe gastroesophageal reflux disease (GERD); or symptoms of dysphagia (eg, difficulty swallowing, food “getting stuck”). 4. Recurrent GI symptoms considered clinically significant in the opinion of the investigator. 5. History of a mast cell disorder including mastocytosis, urticaria pigmentosa, chronic idiopathic or chronic physical urticaria beyond simple dermatographism (eg, cold urticaria, cholinergic urticaria), and hereditary or idiopathic angioedema. 6. Moderate or severe persistent asthma (criteria steps 3-6; National Heart, Lung, and Blood Institute [NHLBI], 2007). 7. Mild asthma (criteria steps 1-2; NHLBI, 2007) that is uncontrolled or difficult to control based on NHLBI 2007 criteria. 8. History of high-dose corticosteroid use (eg, 1-2 mg/kg prednisone or equivalent for > 3 days) by any route of administration as defined by any of the following: • Steroid administered daily for > 1 month within 1 year before screening • One steroid course within 6 months before screening • More than 2 steroid courses ≥ 1 week in duration within 1 year before screening 9. History of food protein-induced enterocolitis syndrome (FPIES) within 12 months before screening. 10. Recurrent urticaria. 11. History of failure to thrive or any other form of abnormal growth, or developmental or speech delay that precludes age-appropriate communication. 12. History of chronic disease (except mild intermittent asthma, mild persistent asthma that is controlled, atopic dermatitis, or allergic rhinitis) that is or is at significant risk of becoming unstable or requiring a change in a chronic therapeutic regimen. 13. Unable to discontinue antihistamines and other medications that could interfere with the assessment of an allergic reaction for 5 half-lives of the medication before the screening SPT, first day of dose escalation, and DBPCFCs. 14. Use or anticipated use of a prohibited medication (eg, beta blockers [oral], angiotensin converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, or tricyclic antidepressants), monoclonal antibody, or any other immunomodulatory therapy (including immunosuppressive medications). 15. Treatment with any form of immunotherapy for any food allergy anytime before screening. 16. Participation in another clinical trial within 30 days or 5 half-lives of the investigational product, whichever is longer, before screening. 17. Allergy to oat or rice. 18. Hypersensitivity to epinephrine or any of the excipients in the epinephrine auto-injector. 19. Parent/caregiver unable or unwilling to use epinephrine auto-injectors. 20. Unable to follow the protocol requirements. 21. Any other condition (concurrent disease, infection, comorbidity, or psychiatric or psychological disorders) or reason that may interfere with the ability to participate in the study, cause undue risk, or complicate the interpretation of data, in the opinion of the investigator or medical monitor. 22. Resides at the same place as another subject in any AR101 interventional trial. 23. Lives in the same household and/or is a family member of a sponsor employee or site staff involved in conducting this study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the proportion of subjects treated with AR101 compared with placebo who tolerate an at least 1000 mg single dose of peanut protein with no more than mild allergy symptoms during the exit DBPCFC. The Farrington-Manning test will be used to test the null hypothesis that the difference in desensitization response rate is 0 at the two-sided 0.05 significance level. Desensitization response rates and associated 95% CIs will be presented for each treatment group using exact Clopper-Pearson CIs. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After approximately 12 months of treatment |
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E.5.2 | Secondary end point(s) |
• Proportion of subjects who tolerate an at least 600 mg single dose of peanut protein with no more than mild allergy symptoms during the exit DBPCFC. • Proportion of subjects who tolerate an at least 300 mg single dose of peanut protein with no more than mild allergy symptoms during the exit DBPCFC. • The maximum severity of allergy symptoms after consuming peanut protein during the exit DBPCFC. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
United States |
France |
Germany |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last assessment for the last subject in the study |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 30 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 30 |