| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| 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.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The primary objective is to demonstrate the efficacy of AR101, a pharmaceutical-grade peanut allergen formulation, through reduction in clinical reactivity to limited amounts of peanut allergen in peanut-allergic children (ages 4-17 years, inclusive). |
|
| E.2.2 | Secondary objectives of the trial |
1. To demonstrate the safety of AR101 as measured by the incidence of adverse events, including serious adverse events in children (ages 4-17 years, inclusive).
2. To evaluate the immunological effects of peanut OIT therapy in children (ages 4-17 years, inclusive). |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Age 4 through 55 years (inclusive)
2. Clinical history of allergy to peanuts or peanut-containing foods
3. Serum IgE to peanut of ≥ 0.35 kUA/L [determined by UniCAPTM within the past 12 months] and/or a SPT to peanut ≥ 3 mm compared to control
4. Experience dose-limiting symptoms at or before the 100 mg challenge dose of peanut protein (measured as 200 mg of peanut flour) on Screening DBPCFC conducted in accordance with PRACTALL (Practical Issues in Allergology, Joint United States/European Union Initiative) guidelines
5. Written informed consent from adult subjects
6. Written informed consent from parent/guardian for minor subjects
7. Written assent from minor subjects as appropriate (eg, above the age of 7 years or the applicable age per local regulatory requirements)
8. Use of effective birth control by female subjects of child-bearing potential
9. Not be residing at the same address as another subject in this or any peanut OIT study
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|
| E.4 | Principal exclusion criteria |
1. History of cardiovascular disease, including uncontrolled or inadequately controlled hypertension (see also Section 5.10 Prohibited Medications)
2. History of severe or life-threatening episode of anaphylaxis or anaphylactic shock within 60 days of Screening DBPCFC
3. History of chronic disease (other than asthma, atopic dermatitis, or allergic rhinitis) that is, or is at significant risk of becoming, unstable or requiring a change in chronic therapeutic regimen
4. History of eosinophilic esophagitis (EoE), other eosinophilic gastrointestinal disease, chronic, recurrent, or severe gastroesophageal reflux disease (GERD), symptoms of dysphagia (eg, difficulty swallowing, food “getting stuck”), or recurrent gastrointestinal symptoms of undiagnosed etiology
5. Current participation in any other interventional study
6. Subject is in “build-up phase” of immunotherapy to another allergen (ie, has not reached maintenance dosing)
7. Severe asthma (2007 NHLBI Criteria Steps 5 or 6, see Appendix 2)
8. Mild or moderate asthma (2007 NHLBI Criteria Steps 1-4), if uncontrolled or difficult to control as defined by any of the following:
1. Forced expiratory volume in 1 second (FEV1) < 80% of predicted, or ratio of FEV1 to forced vital capacity (FEV1/FVC) < 75% of predicted, with or without controller medications (only for age 6 or greater and able to do spirometry) or
2.Inhaled corticosteroid (ICS) dosing of > 500 mcg daily fluticasone (or equivalent ICSs based on National Heart, Lung, and Blood Institute [NHLBI] dosing chart) or
3. One hospitalization in the past year prior to screening for asthma or
4. Emergency room (ER) visit for asthma within 6 months prior to screening
9. History of steroid medication use (via intravenous [IV], intramuscular [IM] or oral administration) in any of the following manners:
10. History of daily oral steroid dosing for > 1 month during the past year or
11. Burst oral (IM or IV) steroid course in the past 3 months prior to randomization or
12. > 2 burst oral (IM or IV) steroid courses in the past year ≥1 week in duration
13. Inability to discontinue antihistamines 5 half-lives before the initial day of escalation, skin prick testing, or DBPCFC
14. Lack of an available palatable vehicle food to which the subject is not allergic
15. Use of any therapeutic antibody (eg omalizumab, mepolizumab, reslizumab, etc.), any investigational peanut immunotherapy (eg oral, sublingual, epicutaneous), or any other immunomodulatory therapy excluding corticosteroids within the past 6 months (see also Section 5.10 Prohibited Medications)
16. Use of beta-blockers (oral), angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARB) or calcium channel blockers (see also Section 5.10 Prohibited Medications)
17. Pregnancy or lactation
18. Having the same place of residence as another subject in the study
19. Participation in another clinical trial within 30 days or 5 half-lives of the investigational product, whichever is longer, prior to randomization
20. Developing dose limiting symptoms in reaction to the placebo part of the Screening DBPCFC
21. History of a mast cell disorder, including mastocytosis, urticaria pigmentosa, and hereditary or idiopathic angioedema
22. Allergy to oat
23. Hypersensitivity to epinephrine and any of the excipients in the product
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary clinical efficacy endpoint is the proportion of subjects aged 4 to 17 years who tolerate a single highest dose of at least 1000 mg (2043 mg cumulative) of peanut protein with no more than mild symptoms at the Exit DBPCFC |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| After approximately 12 months treatment including 6 months at maintenance dose of 300mg/day |
|
| E.5.2 | Secondary end point(s) |
1. The proportion of subjects aged 4 to 17 years who tolerate a single highest dose of at least 600 mg (1043 mg cumulative) of peanut protein with no more than mild symptoms at the Exit DBPCFC
2. The proportion of subjects aged 4 to 17 years who tolerate a single highest dose of at least 300 mg (443 mg cumulative) of peanut protein with no more than mild symptoms at the Exit DBPCFC
3. The maximum severity of symptoms in subjects aged 4 to 17 years occurring at any challenge dose of peanut protein during the Exit DBPCFC
4. The proportion of subjects aged 18 to 55 years who tolerate a single highest dose of at least 1000 mg (2043 mg cumulative) of peanut protein with no more than mild symptoms at the Exit DBPCFC
5. Maximum dose achieved with no or mild symptoms at Exit DBPCFC in subjects aged 4 to 17 years
6. Change from baseline in maximum tolerated dose (MTD) of peanut protein at DBPCFC in subjects aged 4 to 17 years
7. Use of epinephrine as a rescue medication at Exit DBPCFC and comparison to its use at Screening DBPCFC in subjects aged 4 to 17 years
8. Changes in peanut-specific serum IgE and IgG4 levels in subjects aged 4 to 17 years
9. Changes in peanut skin prick test (SPT) mean wheal diameters in subjects aged 4 to 17 years
10. Quality of life assessment using the food allergy related quality of life questionnaire (FAQLQ), and the food allergy independent measure (FAIM) questionnaire in subjects aged 4 to 17 years |
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | Yes |
| 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
| Yes |
| 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 | 15 |
| 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 |
| Canada |
| Denmark |
| Germany |
| Ireland |
| Italy |
| Netherlands |
| Spain |
| Sweden |
| United Kingdom |
| United States |
|
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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