Eosinophilic EsophagitisPhase 3MESSINANCT04543409
A Study of Benralizumab in Patients With Eosinophilic Esophagitis
A Phase 3 study testing Benralizumab in people with Eosinophilic Esophagitis, run by AstraZeneca at 78 sites in 12 countries.
Trial summary
The aim of this Phase 3 study is to investigate the use of benralizumab as a treatment for patients with EoE. The effect of doses of benralizumab on EoE histologic signs and symptoms will be assessed over a 52-week treatment period (including a 24-week double-blind placebo-controlled treatment period and a 28-week… Read more about this study
- Who is it for?
- Ages 12 to 65 years
- Conditions the study is for
- Eosinophilic Esophagitis
- What is being tested?
- Benralizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 211 participants
- Where
- 78 sitesin 12 countries
- Study dates
- 22 Sep 2020to 6 Feb 2023
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients 12 to 65 years of age, inclusive, at the time of signing the informed consent or assent (if applicable) form.
- Documented previous diagnosis of EoE by endoscopy.
- Must be symptomatic at Visit 1 (screening) and Visit 2 (randomization):
- A patient reported an average of at least 2 days per week with an episode of dysphagia over the 4 weeks prior to Visit 1 AND
- An average of at least 2 days per week with an episode of dysphagia (Daily DSQ ≥2) between Visit 1 and Visit 2, and at least 2 days per week with an episode of dysphagia (Daily DSQ ≥2) in each of the 2 weeks immediately prior to randomization
- May be on background medications for EoE and related treatments during the study as long as the background medications have been stable for at least 4 weeks (8 weeks for PPI) prior to the screening and there is agreement not to change type of background medication or dosage during the run-in period and for the first 52 weeks of the study unless a change is medically indicated.
- Negative serum pregnancy test for female patients of childbearing potential at Visit1.
- Women of childbearing potential must agree to use a highly effective form of birth control (confirmed by the Investigator) from randomization throughout the study duration and within 12 weeks after last dose if IP.
Who cannot join
- Other GI disorders such as active Helicobacter pylori infection, history of achalasia, esophageal varices, Crohn's disease, ulcerative colitis, inflammatory bowel disease, or celiac disease.
- Esophageal stricture that prevents the easy passage of a standard endoscope or any critical esophageal stricture that requires dilation during the run-in period.
- Esophageal dilation performed within 8 weeks prior to screening and prior esophageal surgery that would impact the assessments for EoE
- Use of a feeding tube, or having a pattern of not eating solid food daily during the run-in period.
- Hypereosinophilic syndrome, defined by multiple organ involvement and persistent blood eosinophil count >1500 eos/μL.
- EGPA vasculitis.
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- Eosinophilic gastritis, gastroenteritis, enteritis, or colitis documented by biopsy.
- Current malignancy, or history of malignancy with some specific exceptions.
- History of anaphylaxis to any biologic therapy or vaccine.
- Current active liver disease:
- Chronic stable hepatitis B and C (including positive testing for hepatitis B surface antigen [HBsAg] or hepatitis C antibody), or other stable chronic liver disease are acceptable if patient otherwise meets eligibility criteria.
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥3 times the upper limit of normal (ULN), confirmed by repeated testing during the run-in period.
- Helminth parasitic infection diagnosed within 24 weeks prior to the date informed consent or assent (if applicable) is obtained that has not been treated with or has failed to respond to standard of care therapy.
- History of known immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test.
- Concomitant use of immunosuppressive medication.
- Initiation or change of a food-elimination diet regimen or reintroduction of a previously eliminated food group in the 6 weeks prior to start of the run-in period.
- Currently pregnant, breastfeeding, or lactating women.
Trial locations and contacts
78 sites in 12 countries.
78 sites in 12 countries
United States22 sites
Research Site
Atlanta, Georgia, 30322-1013
Research Site
Boston, Massachusetts, 02111
Research Site
Boston, Massachusetts, 02115
Research Site
Chapel Hill, North Carolina, 27514
Research Site
Chesterfield, Michigan, 48047
Research Site
Chicago, Illinois, 60611
Research Site
Cincinnati, Ohio, 45229
Research Site
Lincoln, Nebraska, 68510
Research Site
Little Rock, Arkansas, 72202
Research Site
New York, New York, 10029
Research Site
Normal, Illinois, 61761
Research Site
Ocean City, New Jersey, 07712
Research Site
Park Ridge, Illinois, 60068
Research Site
Philadelphia, Pennsylvania, 19104
Research Site
Richmond, Virginia, 23219
Research Site
Rochester, Minnesota, 55905
Research Site
Salt Lake City, Utah, 84107
Research Site
Salt Lake City, Utah, 84132
Research Site
St. Petersburg, Florida, 33709
Research Site
Uniontown, Pennsylvania, 15401
Research Site
White Marsh, Maryland, 21162
Research Site
Winston-Salem, North Carolina, 27157
Poland8 sites
Research Site
Gdansk, 80-214
Research Site
Knurów, 44-190
Research Site
Lodz, 93-338
Research Site
Lublin, 20-582
Research Site
Rzeszów, 35-302
Research Site
Szczecin, 71-434
Research Site
Warsaw, 04-141
Research Site
Wroclaw, 50-449
France7 sites
Research Site
Dijon, 21079
Research Site
Lille, 59037
Research Site
Lille, F-59037
Research Site
Lyon, 69437
Research Site
Pessac, 33600
Research Site
Suresnes, 92151
Research Site
Toulouse, 31059
Spain7 sites
Research Site
Badalona, 08916
Research Site
Barcelona, 08035
Research Site
Barcelona, 08036
Research Site
Bilbao, 48013
Research Site
Madrid, 28006
Research Site
Madrid, 28031
Research Site
Madrid, 28040
Italy6 sites
Research Site
Florence, 50134
Research Site
Genova, 16126
Research Site
Naples, 80131
Research Site
Pisa, 56124
Research Site
Rozzano, 20089
Research Site
Verona, 37134
Israel5 sites
Research Site
Afula, 18341
Research Site
Holon, 58100
Research Site
Kfar Saba, 4428164
Research Site
Petah Tikva, 4920235
Research Site
Tel Aviv, 64239
Canada4 sites
Research Site
Hamilton, Ontario, L8S 1G5
Research Site
London, Ontario, N6A 5W9
Research Site
Ottawa, Ontario, K1H 1E4
Research Site
Windsor, Ontario, N8X 2G1
Germany4 sites
Research Site
Frankfurt, 60590
Research Site
München, 80337
Research Site
München, 81675
Research Site
Remscheid, 42859
Japan4 sites
Research Site
Chiba, 260-0877
Research Site
Izumo-shi, 693-8501
Research Site
Maebashi, 371-8511
Research Site
Osaka, 545-8586
Russia4 sites
Research Site
Chelyabinsk, 454091
Research Site
Moscow, 105066
Research Site
Moscow, 111123
Research Site
Moscow, 119992
United Kingdom4 sites
Research Site
Brighton, BN2 5BE
Research Site
Darlington, DL3 6HX
Research Site
London, E1 2AJ
Research Site
London, SW17 0RE
Netherlands3 sites
Research Site
Amsterdam, 1105 AZ
Research Site
Nieuwegein, 3435 CM
Research Site
Nijmegen, 6525 GA
About this study
Official title: A Multicenter, Randomized, Double-blind, Parallel-group, Placebo Controlled Study to Investigate the Use of Benralizumab for Eosinophilic Esophagitis
The aim of this Phase 3 study is to investigate the use of benralizumab as a treatment for patients with EoE. The effect of doses of benralizumab on EoE histologic signs and symptoms will be assessed over a 52-week treatment period (including a 24-week double-blind placebo-controlled treatment period and a 28-week open-label treatment period). It is proposed that benralizumab will deplete eosinophils from GI tissue(s), improve the symptoms of dysphagia, and improve endoscopy scores as well as other markers of disease activity. Upon completion of the initial 52-week treatment period, patients will be offered an additional Open Label Extension period of at least 1 year, with benralizumab treatment and ongoing study assessments.
- Conditions
- Eosinophilic Esophagitis
- Being tested
- Benralizumab, Matching placebo
- Keywords
- Eosinophilic Esophagitis, EoE, Benralizumab
- Medical subject headings
- Eosinophilic Esophagitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BenralizumabBiological
Solution for injection in a single accessorized prefilled syringe (APFS) will be administered subcutaneously (SC), 1 mL fill volume
Matching placeboBiological
Matching placebo solution for injection in APFS, 1 mL fill volume. Placebo solution will be administered subcutaneously (SC), 1 mL fill volume
| Study group | Role | What they receive |
|---|---|---|
| Benralizumab | Experimental | Benralizumab active solution will be administered SC to patients by healthcare professionals in this clinical study using an accessorized prefilled syringe (APFS) Receives: Biological: Benralizumab |
| Placebo | Placebo comparator | Placebo solution will be administered SC to patients by healthcare professionals in this clinical study using an accessorized prefilled syringe (APFS) Receives: Biological: Matching placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Patients With a Histologic Response, Defined as a Peak Esophageal Intraepithelial Eosinophil Count ≤ 6 Eos/Hpf.
Percentage of patients with a histologic response at Week 24 and Week 52. A histologic response is defined as a peak esophageal intraepithelial eosinophil count <= 6 eos/hpf across all available esophageal levels. Subjects with no biopsy data at Week 24 or with intercurrent events prior to Week 24 such as changes to background medications or additional new therapies for EoE are considered non-responders.
The number analyzed represents the number of participants in the treatment group that could have made it to the timepoint by the data cut off.
Measured: Week 24, Week 52
Changes From Baseline in Dysphagia Symptom Questionnaire (DSQ)
The Dysphagia Symptom Questionnaire (DSQ) captures the presence and severity of dysphagia symptoms in the past day in a 4-item questionnaire. The DSQ score is calculated over 14-day periods and ranges from 0 to 84, with a lower score indicating less severe dysphagia. At least 8 days with evaluable daily score in 14-day period are required; otherwise the DSQ score for the period is set to missing.
The number analyzed represents the number of participants with data at that visit (including patients with imputed values post intercurrent events).
Measured: Week 24, Week 52
Secondary outcomes (22)
Percent Change From Baseline in Tissue Eosinophils
Percent change from baseline in tissue eosinophils (eos) at Week 24 and Week 52.
The number analyzed represents the number of participants with data at that visit (including imputed values).
Measured: Week 24, Week 52
Change From Baseline in Eosinophilic Esophagitis-Histology Scoring System (EoE-HSS) Total Grade Score at Week 24
EoE-HSS Grade and Stage Scores evaluate eight features: eosinophil density, basal zone hyperplasia, eosinophil abscesses, eosinophil surface layering, dilated intercellular spaces, surface epithelial alteration, dyskeratotic epithelial cells, and lamina propria fibrosis. Severity (grade) and extent (stage) of abnormalities will be scored using a 4-point scale (0 normal; 3 maximum change). Total grade score (TGS): mean of the grade score ratios per region. Grade score ratio per region is the sum of all available feature grade scores divided by the maximum possible score. The maximum possible total grade score is 1.
The number analyzed represents the number of participants with data at that visit (including imputed values).
Measured: Week 24
Change From Baseline in Eosinophilic Esophagitis-Histology Scoring System (EoE-HSS) Total Stage Score at Week 24
EoE-HSS Grade and Stage Scores evaluate eight features: eosinophil density, basal zone hyperplasia, eosinophil abscesses, eosinophil surface layering, dilated intercellular spaces, surface epithelial alteration, dyskeratotic epithelial cells, and lamina propria fibrosis. Severity (grade) and extent (stage) of abnormalities will be scored using a 4-point scale (0 normal; 3 maximum change). Total stage score (TSS): mean of the stage score ratios per region. Stage score ratio per region is the sum of all available feature stage scores divided by the maximum possible score. The maximum possible total stage score is 1.
The number analyzed represents the number of participants with data at that visit (including imputed values).
Measured: Week 24
Changes From Baseline in Centrally-read Endoscopic Reference Score (EREFS)
EREFS is a scoring system for assessing the presence and severity of the major endoscopic signs of EoE.The score ranges from 0 (normal) to 9 (severe disease). EREFS total score (TS): The worst score for each individual component from the proximal and distal scores were summed to form the EREFS total score (TS).
The number analyzed represents the number of participants with data at that visit (including patients with imputed values post intercurrent events).
Measured: Week 24, Week 52
Treatment Responder Rate at Week 24, Defined as a Composite of Histological Response (≤6eos/Hpf) and Clinically Meaningful Improvement From Baseline in Dysphagia Symptom Questionnaire (DSQ) (30% Improvement) at Week 24
Percentage of participants with a treatment response at Week 24. A treatment response is defined as composite of histologic response and clinically meaningful improvement (30% reduction) from baseline in DSQ score. Participants with missing data at Week 24 or with intercurrent events prior to Week 24 are considered non-responders.
Measured: Week 24
Centrally-read Biopsies for Additional Histopathology Including Tissue Eosinophil Counts at Week 24
Esophagogastroduodenoscopy biopsies were collected at week 24 and sent to the central lab for slide preparation and for central, blinded pathology review of tissue eosinophil counts and histopathology. Centralized slide assessments and scoring from an independent physician review was performed for all biopsies.
Measured: Week 24
Dysphagia-free Days as Captured by the Dysphagia Symptom Questionnaire (DSQ)
Dysphagia free days is a count ranging from 0-28. Higher counts indicate better outcomes.
The number analyzed represents the number of participants with data at that visit.
Measured: Week 24, Week 52
Frequency of Dysphagia Episodes as Captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D)
EoE-3D is a daily diary focused on the patient experience of EoE. Dysphagia episode frequency is summarized as the total number of dysphagia episodes occurring over each 28-day period following randomization, scaled up to 28 days based on missing days. Requires at least 8 days of evaluable data in each 14-day period within each 28-day period; otherwise the period is set to missing.
The number analyzed represents the number of participants with data at that visit.
Measured: Week 24, Week 52
Changes From Baseline in Dysphagia Associated Pain, Discomfort, and Overall Severity as Captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D) at Week 24
In the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D), patients report on whether they experienced episodes of difficulty swallowing in the past 24 hours and if so, how many. Patients respond to 3 questions on the pain, discomfort, and overall severity of the event using a numeric rating scale (0 [no] to 10 [worst]). This is repeated for each episode reported. Each category score is calculated as the sum of daily average values in the 14-day period divided by the number of days with available episodes of difficulty swallowing episodes during the same 14-day period (each of the three final scores range from 0 to 10, with higher values indicating a worse outcome in that category). Requires at least 8 days of evaluable data during the period; otherwise, the mean scores are set to missing. Days with 0 episodes of difficulty swallowing count as evaluable. In case all 14 days with 0 episode of difficulty swallowing, the score is set to missing.
Measured: Week 24
Changes From Baseline in Dysphagia Associated Pain, Discomfort, and Overall Severity as Captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D) at Week 52
In the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D), patients report on whether they experienced episodes of difficulty swallowing in the past 24 hours and if so, how many. Patients respond to 3 questions on the pain, discomfort, and overall severity of the event using a numeric rating scale (0 [no] to 10 [worst]). This is repeated for each episode reported. Each category score is calculated as the sum of daily average values in the 14-day period divided by the number of days with available episodes of difficulty swallowing episodes during the same 14-day period (each of the three final scores range from 0 to 10, with higher values indicating a worse outcome in that category). Requires at least 8 days of evaluable data during the period; otherwise, the mean scores are set to missing. Days with 0 episodes of difficulty swallowing count as evaluable. In case all 14 days with 0 episode of difficulty swallowing, the score is set to missing.
Measured: Week 52
Changes From Baseline in Abdominal Pain and Nausea as Captured by the Daily Diary at Week 24
In the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D), respondents are asked to report the severity of abdominal pain and the severity of nausea at their worst over the past 24 hours using an 11-point numeric rating scale (0 [no] to 10 [worst]). Abdominal pain severity and nausea severity will be summarized individually as 14-day mean scores. Each 14-day mean score will be calculated as the sum of daily numerical rating scale score responses divided by the number of days with evaluable data in the same 14-day period. Calculation of the 14-day means will require at least 8 out of 14 days of evaluable data; otherwise, the mean score will be set to missing.
The number analyzed represents the number of participants with data at that visit (including participants with imputed values post intercurrent events).
Measured: Week 24
Changes From Baseline in Abdominal Pain and Nausea as Captured by the Daily Diary at Week 52
In the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D), respondents are asked to report the severity of abdominal pain and the severity of nausea at their worst over the past 24 hours using an 11-point numeric rating scale (0 [no] to 10 [worst]). Abdominal pain severity and nausea severity will be summarized individually as 14-day mean scores. Each 14-day mean score will be calculated as the sum of daily numerical rating scale score responses divided by the number of days with evaluable data in the same 14-day period. Calculation of the 14-day means will require at least 8 out of 14 days of evaluable data; otherwise, the mean score will be set to missing.
The number analyzed represents the number of participants with data at that visit (including participants with imputed values post intercurrent events).
Measured: Week 52
Changes From Baseline in the Pediatric Eosinophilic Esophagitis Symptom Severity Module (PEESS)
The Pediatric Eosinophilic Esophagitis Symptom Severity Module, Version 2, Children and Teens Report (PEESS) is an 18-item assessment of EoE symptom severity and frequency validated for use in patients age 8 to 18 years. The recall period is one month. The first 18 questions alternate between a question about a given symptom's frequency (never=0, almost never=1, sometimes=2, often=3, almost always=4) and a question about the symptom's severity (face rating scale with drawings representing: not bad at all=0, a little bad=1, kind of bad=2, bad=3, very bad=4). The remaining two questions ask about frequency of eating less food than others and frequency of needing more time to eat than others. The overall score ranges from 0 to 80, with higher scores representing more severe and frequent EoE symptoms.
The number analyzed represents the number of participants with data at that visit.
Measured: Week 24, Week 52
Changes From Baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EOE-QoL-A) at Week 24
The Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EoE-QoL-A) is a 30-item assessment developed specifically to measure health-related quality of life in patients with EoE. Responses are on a 5-point scale: Not at all = 4, Slightly = 3, Moderately = 2, Quite a Bit = 1, Extremely = 0. The assessment has 5 domains: eating/diet impact, social impact, emotional impact, disease anxiety and swallowing anxiety.
Domain scores are calculated as follows:
- Eating/Diet Impact (range 0 to 40): sum of Q2, Q9, Q16, Q24, Q25, Q26, Q27, Q28, Q29, Q30
- Social Impact (range 0 to 16): sum of Q14, Q17, Q19, Q22
- Emotional Impact (range 0 to 32): sum of Q1, Q5, Q6, Q7, Q11, Q13, Q21, Q23
- Disease Anxiety (range 0 to 20): sum of Q4, Q10, Q12, Q15, Q18,
- Swallowing Anxiety (range 0 to 12): sum of Q3, Q8, Q20 The total score (range 0 to 120) is calculated as the sum of all responses. Lower scores indicate a greater degree of impairment. Higher scores indicate a better quality of life.
Measured: Week 24
Changes From Baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EOE-QoL-A) at Week 52
The Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EoE-QoL-A) is a 30-item assessment developed specifically to measure health-related quality of life in patients with EoE. Responses are on a 5-point scale: Not at all = 4, Slightly = 3, Moderately = 2, Quite a Bit = 1, Extremely = 0. The assessment has 5 domains: eating/diet impact, social impact, emotional impact, disease anxiety and swallowing anxiety.
Domain scores are calculated as follows:
- Eating/Diet Impact (range 0 to 40): sum of Q2, Q9, Q16, Q24, Q25, Q26, Q27, Q28, Q29, Q30
- Social Impact (range 0 to 16): sum of Q14, Q17, Q19, Q22
- Emotional Impact (range 0 to 32): sum of Q1, Q5, Q6, Q7, Q11, Q13, Q21, Q23
- Disease Anxiety (range 0 to 20): sum of Q4, Q10, Q12, Q15, Q18,
- Swallowing Anxiety (range 0 to 12): sum of Q3, Q8, Q20 The total score (range 0 to 120) is calculated as the sum of all responses. Lower scores indicate a greater degree of impairment. Higher scores indicate a better quality of life.
Measured: Week 52
Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 24
The Short Form 36-item Health Survey, version 2, acute recall (SF-36v2) is a 36-item, self-report survey of functional health and well-being, with a 1-week recall period. There are 8 domain scores: Physical Functioning (PF), Role Limitations due to Physical Health (RP), Bodily Pain (BP), General Health Perceptions (GH), Vitality (VT), Social Functioning (SF), Role Limitations due to Emotional Problems (RE), and Mental Health (MH). Psychometrically-based physical and mental health component summary scores (PCS and MCS, respectively) were computed from subscale scores to give a broader metric of physical and mental health-related quality of life. All scores range from 0-100, with higher scores meaning better outcomes.
The number analyzed represents the number of participants with data at that visit (including participants with imputed values post intercurrent events).
Measured: Week 24
Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 52
The Short Form 36-item Health Survey, version 2, acute recall (SF-36v2) is a 36-item, self-report survey of functional health and well-being, with a 1-week recall period. There are 8 domain scores: Physical Functioning (PF), Role Limitations due to Physical Health (RP), Bodily Pain (BP), General Health Perceptions (GH), Vitality (VT), Social Functioning (SF), Role Limitations due to Emotional Problems (RE), and Mental Health (MH). Psychometrically-based physical and mental health component summary scores (PCS and MCS, respectively) were computed from subscale scores to give a broader metric of physical and mental health-related quality of life. All scores range from 0-100, with higher scores meaning better outcomes.
The number analyzed represents the number of participants with data at that visit (including participants with imputed values post intercurrent events).
Measured: Week 52
Percent of Patients With Relevant Concomitant Procedures and Healthcare Resource Utilization at Week 24 and Week 52.
Percent of patients with any relevant concomitant procedures or healthcare resource utilization for Eosinophilic esophagitis (EoE) or an EoE-related episode (e.g., an intervention for food impaction or stricture requiring dilatation) since last healthcare resource utilization assessment during the previous scheduled visit. Assessed at Week 24 and Week 52.
Measured: Week 24, Week 52
Patient Reported Overall Severity of Disease as Measured by Patient Global Impression of Severity (PGI-S) at Week 24
Patient Global Impression of Severity (PGI-S) is an assessment of the patient's perceived disease severity. The answer options are "no symptoms," "very mild," "mild," "moderate," "severe," and "very severe."
The number analyzed represents the participants with evaluable PGI-S results at that timepoint.
Measured: Week 24
Patient Reported Overall Severity of Disease as Measured by Patient Global Impression of Severity (PGI-S) at Week 52
Patient Global Impression of Severity (PGI-S) is an assessment of the patient's perceived disease severity. The answer options are "no symptoms," "very mild," "mild," "moderate," "severe," and "very severe."
The number analyzed represents the participants with evaluable PGI-S results at that timepoint.
Measured: Week 52
Patient Reported Change in Health Status Since Baseline as Measured by Patient Global Impression of Change (PGI-C) at Week 24
Patient Global Impression of Change (PGI-C) measures the patient's overall impression of response to treatment since the initial dose. The answer options are "much better," "moderately better," "a little better," "about the same/no change," "a little worse," "moderately worse," and "much worse."
The number analyzed represents the participants with evaluable PGI-C results at that timepoint.
Measured: Week 24
Patient Reported Change in Health Status Since Baseline as Measured by Patient Global Impression of Change (PGI-C) at Week 52
Patient Global Impression of Change (PGI-C) measures the patient's overall impression of response to treatment since the initial dose. The answer options are "much better," "moderately better," "a little better," "about the same/no change," "a little worse," "moderately worse," and "much worse."
The number analyzed represents the participants with evaluable PGI-C results at that timepoint.
Measured: Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2020
- Study start22 Sep 2020
- Primary completion19 Sep 2022
- Study completion6 Feb 2023
Why it stopped: High-level results from the MESSINA Phase III trial showed that AstraZeneca's Fasenra (benralizumab) did not meet one of the two dual-primary endpoints. Given the lack of clear benefit in this patient population, study has been terminated.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Eosinophilic EsophagitisStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 211 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Marc E. Rothenberg, MD, PhD, Principal investigator, Children's Hospital Medical Center, Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04543409
- Sponsor's protocol ID
- D3255C00001
- Other IDs
- 2019-002871-32, 2019
- Acronym
- MESSINA
- Status last verified
- Oct 2023
- First submitted
- 18 Aug 2020
- Last updated
- 18 Nov 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Publications
Ho CN, Fjallbrant H, Dellon ES, Santander C, Rothenberg ME, Bailey J, McFadden S, Ritchie J. Patient experience with eosinophilic esophagitis symptoms and impacts on daily life based on in-trial qualitative interviews. J Patient Rep Outcomes. 2025 Jan 8;9(1):3. doi: 10.1186/s41687-025-00836-x.
PubMed 39777591Rothenberg ME, Dellon ES, Collins MH, Bredenoord AJ, Hirano I, Peterson KA, Brooks L, Caldwell JM, Fjallbrant H, Grindebacke H, Ho CN, Keith M, McCrae C, Sinibaldi D, White WI, Datto CJ; MESSINA Trial Investigators. Eosinophil Depletion with Benralizumab for Eosinophilic Esophagitis. N Engl J Med. 2024 Jun 27;390(24):2252-2263. doi: 10.1056/NEJMoa2313318.
PubMed 38924732
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Double-blind, Parallel-group, Placebo Controlled Study to Investigate the Use of Benralizumab for Eosinophilic Esophagitis
- ClinicalTrials.gov ID
- NCT04543409
- Acronym / sponsor ID
- MESSINA / D3255C00001
- Conditions
- Eosinophilic Esophagitis
- Keywords
- Eosinophilic Esophagitis, EoE, Benralizumab
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: High-level results from the MESSINA Phase III trial showed that AstraZeneca's Fasenra (benralizumab) did not meet one of the two dual-primary endpoints. Given the lack of clear benefit in this patient population, study has been terminated.
- Enrolment
- 211 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 22 Sep 2020 (actual)
- Primary completion
- 19 Sep 2022 (actual)
- Study completion
- 6 Feb 2023 (actual)
- First posted
- 10 Sep 2020 (actual)
- Results
- Posted 18 Nov 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of this Phase 3 study is to investigate the use of benralizumab as a treatment for patients with EoE. The effect of doses of benralizumab on EoE histologic signs and symptoms will be assessed over a 52-week treatment period (including a 24-week double-blind placebo-controlled treatment period and a 28-week open-label treatment period). It is proposed that benralizumab will deplete eosinophils from GI tissue(s), improve the symptoms of dysphagia, and improve endoscopy scores as well as other markers of disease activity. Upon completion of the initial 52-week treatment period, patients will be offered an additional Open Label Extension period of at least 1 year, with benralizumab treatment and ongoing study assessments.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Benralizumab | Experimental | Biological: BenralizumabBenralizumab active solution will be administered SC to patients by healthcare professionals in this clinical study using an accessorized prefilled syringe (APFS) |
| Placebo | Placebo comparator | Biological: Matching placeboPlacebo solution will be administered SC to patients by healthcare professionals in this clinical study using an accessorized prefilled syringe (APFS) |
Who may qualify
- Ages
- 12 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- Patients 12 to 65 years of age, inclusive, at the time of signing the informed consent or assent (if applicable) form.
- Documented previous diagnosis of EoE by endoscopy.
- Must be symptomatic at Visit 1 (screening) and Visit 2 (randomization):
- May be on background medications for EoE and related treatments during the study as long as the background medications have been stable for at least 4 weeks (8 weeks for PPI) prior to the screening and there is agreement not to change type of background medication or dosage during the run-in period and for the first 52 weeks of the study unless a change is medically indicated.
- Negative serum pregnancy test for female patients of childbearing potential at Visit1.
Key exclusion criteria (17 listed)
- Other GI disorders such as active Helicobacter pylori infection, history of achalasia, esophageal varices, Crohn's disease, ulcerative colitis, inflammatory bowel disease, or celiac disease.
- Esophageal stricture that prevents the easy passage of a standard endoscope or any critical esophageal stricture that requires dilation during the run-in period.
- Esophageal dilation performed within 8 weeks prior to screening and prior esophageal surgery that would impact the assessments for EoE
- Use of a feeding tube, or having a pattern of not eating solid food daily during the run-in period.
- Hypereosinophilic syndrome, defined by multiple organ involvement and persistent blood eosinophil count >1500 eos/μL.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BenralizumabSolution for injection in a single accessorized prefilled syringe (APFS) will be administered subcutaneously (SC), 1 mL fill volume | Biological | Benralizumab |
| Matching placeboMatching placebo solution for injection in APFS, 1 mL fill volume. Placebo solution will be administered subcutaneously (SC), 1 mL fill volume | Biological | Placebo |
Primary outcome
Percentage of Patients With a Histologic Response, Defined as a Peak Esophageal Intraepithelial Eosinophil Count ≤ 6 Eos/Hpf.
Time frame: Week 24, Week 52
Percentage of patients with a histologic response at Week 24 and Week 52. A histologic response is defined as a peak esophageal intraepithelial eosinophil count <= 6 eos/hpf across all available esophageal levels. Subjects with no biopsy data at Week 24 or with intercurrent events prior to Week 24 such as changes to background medications or additional new therapies for EoE are considered non-responders. The number analyzed represents the number of participants in the treatment group that could have made it to the timepoint by the data cut off.
Changes From Baseline in Dysphagia Symptom Questionnaire (DSQ)
Time frame: Week 24, Week 52
The Dysphagia Symptom Questionnaire (DSQ) captures the presence and severity of dysphagia symptoms in the past day in a 4-item questionnaire. The DSQ score is calculated over 14-day periods and ranges from 0 to 84, with a lower score indicating less severe dysphagia. At least 8 days with evaluable daily score in 14-day period are required; otherwise the DSQ score for the period is set to missing. The number analyzed represents the number of participants with data at that visit (including patients with imputed values post intercurrent events).
22 secondary outcomes
Percent Change From Baseline in Tissue Eosinophils
Time frame: Week 24, Week 52
Change From Baseline in Eosinophilic Esophagitis-Histology Scoring System (EoE-HSS) Total Grade Score at Week 24
Time frame: Week 24
Change From Baseline in Eosinophilic Esophagitis-Histology Scoring System (EoE-HSS) Total Stage Score at Week 24
Time frame: Week 24
Changes From Baseline in Centrally-read Endoscopic Reference Score (EREFS)
Time frame: Week 24, Week 52
Treatment Responder Rate at Week 24, Defined as a Composite of Histological Response (≤6eos/Hpf) and Clinically Meaningful Improvement From Baseline in Dysphagia Symptom Questionnaire (DSQ) (30% Improvement) at Week 24
Time frame: Week 24
Centrally-read Biopsies for Additional Histopathology Including Tissue Eosinophil Counts at Week 24
Time frame: Week 24
Dysphagia-free Days as Captured by the Dysphagia Symptom Questionnaire (DSQ)
Time frame: Week 24, Week 52
Frequency of Dysphagia Episodes as Captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D)
Time frame: Week 24, Week 52
Changes From Baseline in Dysphagia Associated Pain, Discomfort, and Overall Severity as Captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D) at Week 24
Time frame: Week 24
Changes From Baseline in Dysphagia Associated Pain, Discomfort, and Overall Severity as Captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D) at Week 52
Time frame: Week 52
Changes From Baseline in Abdominal Pain and Nausea as Captured by the Daily Diary at Week 24
Time frame: Week 24
Changes From Baseline in Abdominal Pain and Nausea as Captured by the Daily Diary at Week 52
Time frame: Week 52
Changes From Baseline in the Pediatric Eosinophilic Esophagitis Symptom Severity Module (PEESS)
Time frame: Week 24, Week 52
Changes From Baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EOE-QoL-A) at Week 24
Time frame: Week 24
Changes From Baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EOE-QoL-A) at Week 52
Time frame: Week 52
Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 24
Time frame: Week 24
Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 52
Time frame: Week 52
Percent of Patients With Relevant Concomitant Procedures and Healthcare Resource Utilization at Week 24 and Week 52.
Time frame: Week 24, Week 52
Patient Reported Overall Severity of Disease as Measured by Patient Global Impression of Severity (PGI-S) at Week 24
Time frame: Week 24
Patient Reported Overall Severity of Disease as Measured by Patient Global Impression of Severity (PGI-S) at Week 52
Time frame: Week 52
Patient Reported Change in Health Status Since Baseline as Measured by Patient Global Impression of Change (PGI-C) at Week 24
Time frame: Week 24
Patient Reported Change in Health Status Since Baseline as Measured by Patient Global Impression of Change (PGI-C) at Week 52
Time frame: Week 52
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39777591Ho CN, Fjallbrant H, Dellon ES, Santander C, Rothenberg ME, Bailey J, McFadden S, Ritchie J. Patient experience with eosinophilic esophagitis symptoms and impacts on daily life based on in-trial qualitative interviews. J Patient Rep Outcomes. 2025 Jan 8;9(1):3. doi: 10.1186/s41687-025-00836-x.
- Derived from this study: PubMed 38924732Rothenberg ME, Dellon ES, Collins MH, Bredenoord AJ, Hirano I, Peterson KA, Brooks L, Caldwell JM, Fjallbrant H, Grindebacke H, Ho CN, Keith M, McCrae C, Sinibaldi D, White WI, Datto CJ; MESSINA Trial Investigators. Eosinophil Depletion with Benralizumab for Eosinophilic Esophagitis. N Engl J Med. 2024 Jun 27;390(24):2252-2263. doi: 10.1056/NEJMoa2313318.
- This is a poster.Link provided by the sponsor.
- CSR SynopsisLink provided by the sponsor.
- Redacted CSPLink provided by the sponsor.
- Redacted SAPLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marc E. Rothenberg, MD, PhD principal investigator
Children's Hospital Medical Center, Cincinnati
78 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Benralizumab in people with Eosinophilic Esophagitis, run by AstraZeneca at 78 sites in 12 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 78 sites in United States, Poland, France, Spain, Italy and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Nov 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Patients With a Histologic Response, Defined as a Peak Esophageal Intraepithelial Eosinophil Count ≤ 6 Eos/Hpf. (time frame: Week 24, Week 52). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04543409, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2023.