E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Eosinophilic esophagitis (EoE) is a rare, chronic inflammatory disorder triggered by an immune response to foods and aeroantigens and characterized by a combination of esophageal dysfunction and eosinophilic infiltration of the esophagus |
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E.1.1.1 | Medical condition in easily understood language |
Eosinophilic esophagitis (EoE) Allergic Esophagitis |
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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 | 10064220 |
E.1.2 | Term | Eosinophilic esophagitis |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1. To evaluate the effect of tezepelumab on the histologic response in adult and adolescent participants with symptomatic and histologically active EoE 2. To evaluate the effect of tezepelumab on symptom improvement in adult and adolescent participants with symptomatic and histologically active EoE |
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E.2.2 | Secondary objectives of the trial |
1. To evaluate the effect of tezepelumab on the centrally-read EoE EREFS 2. To evaluate the effect of tezepelumab on the centrally-read EoE-HSS 3. To evaluate the long-term effect of tezepelumab on the histologic response 4. To evaluate the long-term effect of tezepelumab on symptom improvement 5. To evaluate the long-term effect of tezepelumab on the centrally-read EoE EREFS 6. To evaluate the effect of tezepelumab on achievement of clinicohistological remission 7. To evaluate the effect of tezepelumab on peak eosinophil count 8. To evaluate the effect of tezepelumab on EoE symptoms in adolescents 9. To evaluate the long-term effect of tezepelumab 10. To evaluate the PK and immunogenicity of tezepelumab |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Participant must be 12 to 80 years of age inclusive, at the time of signing the informed consent/assent.
2. Weight ≥ 40 kg at Visit 1
3. Established diagnosis of EoE with a previous EGD and esophageal biopsy confirming a diagnosis of EoE.
4. Participants who have symptomatic EoE as defined by a history of on average at least 2 episodes of dysphagia (any severity of food going down slowly or being stuck in the throat) per week in the 4 weeks prior to Visit 1.
5. Must remain on a stabilized diet for at least 8 weeks prior to Visit 1 and during the course of the study (stable diet is defined as no initiation of single or multiple elimination diets or reintroduction of previously eliminated food groups).
6. May be on any background medication for EoE, for example PPI and/or STC, during the course of the study, as long as background medications have been stable for at least 8 weeks prior to the screening/run-in period (Visit 1) and there is agreement not to change background medication or dosage unless medically indicated, during the screening/run-in and treatment period.
7. Participants currently leukotriene inhibitors and/or steroid treatments for asthma or allergies that are inhaled or administered intranasally, must report a stable dose for at least 4 weeks prior to the screening/run-in period (Visit 1).
8. If a medication for EoE (including PPI and/or STC) is discontinued prior to the screening/run-in, there should be a washout period of at least 8 weeks prior to Visit 1. Discontinuation of any marketed biologic (monoclonal or polyclonal antibody) should have a washout period of 4 months or 5 half-lives prior to Visit 1, whichever is longer.
9. Participants should have previously documented standard of care treatment, which could include PPI and/or STC and/or diet |
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E.4 | Principal exclusion criteria |
1. Other gastrointestinal disorders such as active Helicobacter pylori infection, history of achalasia, esophageal varices, Crohn's disease, ulcerative colitis, inflammatory bowel disease, celiac disease, eosinophilic enteritis, colitis, diverticulitis, irritable bowel syndrome, or other clinically significant gastrointestinal conditions as per Investigator discretion.
2.Esophageal stricture that prevents the easy passage of a standard endoscope or any critical esophageal stricture that requires dilation at screening.
3. Use of a feeding tube, or having a pattern of not eating solid food ≥ 3 days of the week. Solid food is defined as food that requires chewing before swallowing.
4. Hypereosinophilic syndrome.
5. EGPA vasculitis
6. Esophageal dilation performed within 8 weeks prior to screening. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Histologic response of peak esophageal eosinophil per HPF count of ≤ 6 across all available esophageal levels at Week 24 2. Change from baseline in DSQ score at Week 24 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. Change from baseline in EoE EREFS at Week 24 and Week 52
2. Change from baseline in EoE-HSS grade score at Week 24 and Week 52
3. Change from baseline in EoE-HSS stage score at Week 24 and Week 52
4. Histologic response of peak esophageal eosinophil per HPF count of ≤ 6 across all available esophageal levels at Week 52
5. Change from baseline in DSQ score at Week 52
6. Response of achieving clinico-histological remission at Week 24 and Week 52
7. Change from baseline in peak esophageal eosinophil count (EOS/HPF) at Week 24 and Week 52
8. Changes from baseline in PEESS Module at Week 24 and Week 52 (adolescents only)
9. Serum trough concentrations at Weeks 0, 4, 12, and 52
10. Anti-drug antibody at Weeks 0, 12, 24, and 52 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Varies depending on the endpoint/objective |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 | 3 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 58 |
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 |
New Zealand |
Australia |
Brazil |
Canada |
China |
Israel |
Japan |
United States |
Austria |
Belgium |
Czechia |
Denmark |
Finland |
Germany |
Greece |
Italy |
Netherlands |
Norway |
Slovakia |
Spain |
Sweden |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 10 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 29 |