A study to investigate changes in symptoms and esophageal histology with tezepelumab compared with placebo in patients aged 12 to 80 years old with eosinophilic esophagitis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

30 Jan 2023 → ongoing

Decision date (initial)

2024-08-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

AstraZeneca AB

External identifiers

EU CT number

2023-504277-20-00

EudraCT number

2022-001294-31

ClinicalTrials.gov

NCT05583227

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

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

Secondary objectives 9

1. 1. To evaluate the effect of tezepelumab on the centrally-read EoE EREFS
2. 2. To evaluate the effect of tezepelumab on the centrally-read EoE-HSS
3. 3. To evaluate the long-term effect of tezepelumab on the histologic response
4. 4. To evaluate the long-term effect of tezepelumab on symptom improvement
5. 5. To evaluate the long-term effect of tezepelumab on the centrally-read EoE EREFS
6. 6. To evaluate the effect of tezepelumab on peak eosinophil count
7. 7. To evaluate the effect of tezepelumab on EoE symptoms in adolescents
8. 8. To evaluate the long-term effect of tezepelumab
9. 9. To evaluate the PK and immunogenicity of tezepelumab

Conditions and MedDRA coding

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

Study design 4 periods

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-001613-PIP03-21

Plan to share IPD

Yes

IPD plan description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment https://vivli.org/. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 1. Participant must be 12 to 80 years of age inclusive, at the time of signing the informed consent/assent.
2. 2. Weight ≥ 40 kg at Visit 1
3. 3. Established diagnosis of EoE with a previous EGD and esophageal biopsy confirming a diagnosis of EoE.
4. 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. 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. 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. 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. 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. 9. Participants should have previously documented standard of care treatment, which could include PPI and/or STC and/or diet

Exclusion criteria 6

1. 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. 2. Esophageal stricture that prevents the easy passage of a standard endoscope or any critical esophageal stricture that requires dilation at screening.
3. 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. 4. Hypereosinophilic syndrome.
5. 5. EGPA vasculitis.
6. 6. Esophageal dilation performed within 8 weeks prior to screening.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 1. Histologic response of peak esophageal eosinophil per HPF count of ≤ 6 across all available esophageal levels at Week 24
2. 2. Change from baseline in DSQ score at Week 24

Secondary endpoints 12

1. 1. Change from baseline in EoE EREFS at Week 24 and Week 52
2. 2. Change from baseline in EoE-HSS grade score at Week 24 and Week 52
3. 3. Change from baseline in EoE-HSS stage score at Week 24 and Week 52
4. 4. Histologic response of peak esophageal eosinophil per HPF count of ≤ 6 across all available esophageal levels at Week 52
5. 5. Change from baseline in DSQ score at Week 52
6. 6. Endoscopic response of total EREFS score of 0 to ≤ 2 with no score > 1 for any of the components and no worsening in any individual component from baseline across all esophageal levels (ie, proximal, mid, and distal) at Week 52
7. 7. Endoscopic inflammatory remission of EREFS inflammatory subscore (including edema, exudate, and furrows components) of 0 with no worsening in rings or stricture from baseline across all esophageal levels at Week 52.
8. 8. Total endoscopic remission of total EREFS score of 0 across all esophageal levels at Week 52.
9. 9. Change from baseline in peak esophageal eosinophil count (EOS/HPF) at Week 24 and Week 52
10. 10. Changes from baseline in PEESS Module at Week 24 and Week 52 (adolescents only)
11. 11. Serum trough concentrations at Weeks 0, 4, 12, and 52
12. 12. Anti-drug antibody at Weeks 0, 12, 24, and 52

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

Astraallen Gartuna, Karlebyhus Byggnad 674 Karlebyhus Byggnad 674

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

AZ Clinical Study Info Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AZ Clinical Study Info Center

Locations

13 EU/EEA countries · 53 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 108 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

13 submissions — initial application plus substantial / non-substantial modifications