NCT02379052

Study of Dupilumab in Adult Participants With Active Eosinophilic Esophagitis (EoE)

Completed Phase 2 Results posted Last updated 28 February 2020

What this trial tests

Phase 2 trial testing Dupilumab in Eosinophilic Esophagitis in 47 participants. Completed in 10 July 2017.

Timeline

12 May 2015

Primary endpoint
17 February 2017

10 July 2017

Quick facts

Lead sponsor	Regeneron Pharmaceuticals
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	47
Start date	12 May 2015
Primary completion	17 February 2017
Estimated completion	10 July 2017
Sites	14 locations across United States

Drugs / interventions tested

• Dupilumab (DUPILUMAB) — full drug profile →
• Placebo

Conditions studied

• Eosinophilic Esophagitis — all drugs for Eosinophilic Esophagitis →

Sponsor

Regeneron Pharmaceuticals — full company profile →

Who can join

Adults 18 to 65, any sex, with Eosinophilic Esophagitis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Absolute Change From Baseline in Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Total Score at Week 10 Primary · Baseline, Week 10

The SDI is a PRO used to determine frequency/ intensity of dysphagia (recall period 1-wk). Frequency of dysphagia events is graded on a 5-pt scale: 0=none, 1=1x/wk, 2=several/wk, 3=1x/day, 4=several/day; intensity is graded on a 6-pt scale: 0=swallowing unrestricted, 1=slight sensation of resistance, 2=slight retching with delay, 3=short period of obstruction necessitating intervention, 4=longer-lasting period of obstruction removable by vomiting, 5=long-lasting complete obstruction requiring endoscopic intervention. Total score ranges from 0-9 (higher score indicates worsening symptoms).

Group	Value	95% CI
Placebo	-1.3	± 0.57
Dupilumab 300 mg QW	-3.0	± 0.53

Percent Change From Baseline in Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Total Score at Week 10 Secondary · Baseline, Week 10

The SDI is a PRO used to determine frequency/ intensity of dysphagia (recall period 1-wk). Frequency of dysphagia events is graded on a 5-pt scale: 0=none, 1=1x/wk, 2=several/wk, 3=1x/day, 4=several/day; intensity is graded on a 6-pt scale: 0=swallowing unrestricted, 1=slight sensation of resistance, 2=slight retching with delay, 3=short period of obstruction necessitating intervention, 4=longer-lasting period of obstruction removable by vomiting, 5=long-lasting complete obstruction requiring endoscopic intervention. Total score ranges from 0-9 (higher score indicates worsening symptoms).

Group	Value	95% CI
Placebo	-18.59	± 8.978
Dupilumab 300 mg QW	-45.05	± 8.435

Absolute Change From Baseline in Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Total Score at Week 12 Secondary · Baseline, Week 12

The SDI is a PRO used to determine frequency/intensity of dysphagia (recall period 1-wk). Frequency of dysphagia events is graded on a 5-pt scale: 0=none, 1=1x/wk, 2=several/wk, 3=1x/day, 4=several/day; intensity is graded on a 6-pt scale: 0=swallowing unrestricted, 1=slight sensation of resistance, 2=slight retching with delay, 3=short period of obstruction necessitating intervention, 4=longer-lasting period of obstruction removable by vomiting, 5=long-lasting complete obstruction requiring endoscopic intervention. Total score ranges from 0-9 (higher score indicates worsening symptoms).

Group	Value	95% CI
Placebo	-2.2	± 0.69
Dupilumab 300 mg QW	-2.9	± 0.56

Percent Change From Baseline in Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Total Score at Week 12 Secondary · Baseline, Week 12

The SDI is a PRO used to determine frequency/ intensity of dysphagia (recall period 1-wk). Frequency of dysphagia events is graded on a 5-pt scale: 0=none, 1=1x/wk, 2=several/wk, 3=1x/day, 4=several/day; intensity is graded on a 6-pt scale: 0=swallowing unrestricted, 1=slight sensation of resistance, 2=slight retching with delay, 3=short period of obstruction necessitating intervention, 4=longer-lasting period of obstruction removable by vomiting, 5=long-lasting complete obstruction requiring endoscopic intervention. Total score ranges from 0-9 (higher score indicates worsening symptoms).

Group	Value	95% CI
Placebo	-31.83	± 10.674
Dupilumab 300 mg QW	-42.83	± 8.573

Percentage of Participants Achieving a Reduction of ≥ 3 Points in Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Total Score From Baseline at Week 10 Secondary · Baseline, Week 10

The SDI is a PRO used to determine frequency/ intensity of dysphagia (recall period 1-wk). Frequency of dysphagia events is graded on a 5-pt scale: 0=none, 1=1x/wk, 2=several/wk, 3=1x/day, 4=several/day; intensity is graded on a 6-pt scale: 0=swallowing unrestricted, 1=slight sensation of resistance, 2=slight retching with delay, 3=short period of obstruction necessitating intervention, 4=longer-lasting period of obstruction removable by vomiting, 5=long-lasting complete obstruction requiring endoscopic intervention. Total score ranges from 0-9 (higher score indicates worsening symptoms).

Group	Value	95% CI
Placebo	12.5
Dupilumab 300 mg QW	39.1

Percentage of Participants Achieving a Reduction of ≥ 3 Points in Straumann Dysphagia Instrument (SDI) Patient Reported Outcome (PRO) Total Score From Baseline at Week 12 Secondary · Baseline, Week 12

The SDI is a PRO used to determine frequency/ intensity of dysphagia (recall period 1-wk). Frequency of dysphagia events is graded on a 5-pt scale: 0=none, 1=1x/wk, 2=several/wk, 3=1x/day, 4=several/day; intensity is graded on a 6-pt scale: 0=swallowing unrestricted, 1=slight sensation of resistance, 2=slight retching with delay, 3=short period of obstruction necessitating intervention, 4=longer-lasting period of obstruction removable by vomiting, 5=long-lasting complete obstruction requiring endoscopic intervention. Total score ranges from 0-9 (higher score indicates worsening symptoms).

Group	Value	95% CI
Placebo	12.5
Dupilumab 300 mg QW	39.1

Percent Change From Baseline in Weekly Reported Eosinophilic Esophagitis Activity Index (EEsAI) Patient Reported Outcome (PRO) Score at Week 10 Secondary · Baseline, Week 10

The EEsAI PRO questionnaire includes items related to the intensity and frequency of dysphagia, the influence of specific food groups on dysphagia symptoms, and other symptoms independent of eating or drinking (ie, heartburn, acid regurgitation, and chest pain). The total EEsAI PRO score ranges from 0 to 100 (higher score indicates worsening symptoms). The EEsAI PRO utilizes 24-hour and 1-week recall periods.

Group	Value	95% CI
Placebo	-11.33	± 9.915
Dupilumab 300 mg QW	-34.56	± 9.076

Absolute Change From Baseline in Weekly Reported Eosinophilic Esophagitis Activity Index (EEsAI) Patient Reported Outcome (PRO) Score at Week 10 Secondary · Baseline, Week 10

The EEsAI PRO questionnaire includes items related to the intensity and frequency of dysphagia, the influence of specific food groups on dysphagia symptoms, and other symptoms independent of eating or drinking (ie, heartburn, acid regurgitation, and chest pain). The total EEsAI PRO score ranges from 0 to 100 (higher score indicates worsening symptoms). The EEsAI PRO utilizes 24-hour and 1-week recall periods.

Group	Value	95% CI
Placebo	-9.0	± 5.58
Dupilumab 300 mg QW	-22.9	± 5.01

Percent Change From Baseline in Weekly Reported Eosinophilic Esophagitis Activity Index (EEsAI) Patient Reported Outcome (PRO) Score at Week 12 Secondary · Baseline, Week 12

The EEsAI PRO questionnaire includes items related to the intensity and frequency of dysphagia, the influence of specific food groups on dysphagia symptoms, and other symptoms independent of eating or drinking (ie, heartburn, acid regurgitation, and chest pain). The total EEsAI PRO score ranges from 0 to 100 (higher score indicates worsening symptoms). The EEsAI PRO utilizes 24-hour and 1-week recall periods.

Group	Value	95% CI
Placebo	-3.34	± 12.701
Dupilumab 300 mg QW	-36.99	± 11.168

Absolute Change From Baseline in Weekly Reported Eosinophilic Esophagitis Activity Index (EEsAI) Patient Reported Outcome (PRO) Score at Week 12 Secondary · Baseline, Week 12

The EEsAI PRO questionnaire includes items related to the intensity and frequency of dysphagia, the influence of specific food groups on dysphagia symptoms, and other symptoms independent of eating or drinking (ie, heartburn, acid regurgitation, and chest pain). The total EEsAI PRO score ranges from 0 to 100 (higher score indicates worsening symptoms). The EEsAI PRO utilizes 24-hour and 1-week recall periods.

Group	Value	95% CI
Placebo	-5.0	± 7.06
Dupilumab 300 mg QW	-26.1	± 5.87

Percentage of Participants Achieving ≥ 40% Improvement in Weekly Reported Eosinophilic Esophagitis Activity Index (EEsAI) Patient Reported Outcome (PRO) Score From Baseline at Week 10 Secondary · Baseline, Week 10

The EEsAI PRO questionnaire includes items related to the intensity and frequency of dysphagia, the influence of specific food groups on dysphagia symptoms, and other symptoms independent of eating or drinking (ie, heartburn, acid regurgitation, and chest pain). The total EEsAI PRO score ranges from 0 to 100 (higher score indicates worsening symptoms). The EEsAI PRO utilizes 24-hour and 1-week recall periods.

Group	Value	95% CI
Placebo	8.3
Dupilumab 300 mg QW	26.1

Percentage of Participants Achieving ≥ 40% Improvement in Weekly Reported Eosinophilic Esophagitis Activity Index (EEsAI) Patient Reported Outcome (PRO) Score From Baseline at Week 12 Secondary · Baseline, Week 12

The EEsAI PRO questionnaire includes items related to the intensity and frequency of dysphagia, the influence of specific food groups on dysphagia symptoms, and other symptoms independent of eating or drinking (ie, heartburn, acid regurgitation, and chest pain). The total EEsAI PRO score ranges from 0 to 100 (higher score indicates worsening symptoms). The EEsAI PRO utilizes 24-hour and 1-week recall periods.

Group	Value	95% CI
Placebo	4.2
Dupilumab 300 mg QW	39.1

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse event (AE) information was collected from the time the informed consent was signed until the participant's last study visit. Serious adverse event (SAE) information was collected until the event was considered chronic and/or stable.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo

Serious: 0/24 (0%)

Deaths: 0/24

Dupilumab 300 mg QW

Serious: 3/23 (13%)

Deaths: 0/23

Serious adverse events (3 terms)

Reaction	System	Placebo	Dupilumab 300 mg QW
Food allergy	Immune system disorders	—	—
Blood creatine phosphokinase increased	Investigations	—	—
Abortion spontaneous	Pregnancy, puerperium and perinatal conditions	—	—

Other adverse events (25 terms — click to expand)

Reaction	System	Placebo	Dupilumab 300 mg QW
Injection site erythema	General disorders	—	—
Nasopharyngitis	Infections and infestations	—	—
Nausea	Gastrointestinal disorders	—	—
Injection site inflammation	General disorders	—	—
Injection site rash	General disorders	—	—
Upper respiratory tract infection	Infections and infestations	—	—
Ear pain	Ear and labyrinth disorders	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Dyspepsia	Gastrointestinal disorders	—	—
Oesophageal stenosis	Gastrointestinal disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Injection site pain	General disorders	—	—
Injection site urticaria	General disorders	—	—
Pyrexia	General disorders	—	—
Gastroenteritis viral	Infections and infestations	—	—
Influenza	Infections and infestations	—	—
Sinusitis	Infections and infestations	—	—
Aspartate aminotransferase increased	Investigations	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—
Dizziness	Nervous system disorders	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—

Most-reported serious reactions: Food allergy, Blood creatine phosphokinase increased, Abortion spontaneous.

Data from ClinicalTrials.gov NCT02379052 adverse events section.

Sponsor's own description

The primary objective of the study is to assess the clinical efficacy of repeat subcutaneous (SC) doses of dupilumab, compared with placebo, to relieve symptoms in adult participants with active, moderate to severe Eosinophilic Esophagitis (EoE).

The secondary objectives of the study are:

* To assess the safety, tolerability, and immunogenicity of SC doses of dupilumab in adult participants with active, moderate to severe EoE
* To assess the effect of dupilumab on esophageal eosinophilic infiltration
* To evaluate the pharmacokinetics (PK) of dupilumab in adult participants with EoE

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Pathophysiology of Eosinophilic Esophagitis.
   O'Shea KM, Aceves SS, Dellon ES, Gupta SK, et al · · 2018 · cited 376× · PMID 28757265 · DOI 10.1053/j.gastro.2017.06.065
2. Efficacy of Dupilumab in a Phase 2 Randomized Trial of Adults With Active Eosinophilic Esophagitis.
   Hirano I, Dellon ES, Hamilton JD, Collins MH, et al · · 2020 · cited 329× · PMID 31593702 · DOI 10.1053/j.gastro.2019.09.042
3. Conjunctivitis in dupilumab clinical trials.
   Akinlade B, Guttman-Yassky E, de Bruin-Weller M, Simpson EL, et al · · 2019 · cited 303× · PMID 30851191 · DOI 10.1111/bjd.17869
4. Dupilumab suppresses type 2 inflammatory biomarkers across multiple atopic, allergic diseases.
   Hamilton JD, Harel S, Swanson BN, Brian W, et al · · 2021 · cited 139× · PMID 34037993 · DOI 10.1111/cea.13954
5. Interleukin-13 in Asthma and Other Eosinophilic Disorders.
   Doran E, Cai F, Holweg CTJ, Wong K, et al · · 2017 · cited 101× · PMID 29034234 · DOI 10.3389/fmed.2017.00139
6. Eosinophilic esophagitis: clinical, endoscopic, histologic and therapeutic differences and similarities between children and adults.
   Visaggi P, Savarino E, Sciume G, Chio TD, et al · · 2021 · cited 60× · PMID 33613690 · DOI 10.1177/1756284820980860
7. A review of dupilumab in the treatment of atopic diseases.
   Thibodeaux Q, Smith MP, Ly K, Beck K, et al · · 2019 · cited 59× · PMID 30785362 · DOI 10.1080/21645515.2019.1582403
8. Eosinophilic Esophagitis: Review and Update.
   Gomez Torrijos E, Gonzalez-Mendiola R, Alvarado M, Avila R, et al · · 2018 · cited 38× · PMID 30364207 · DOI 10.3389/fmed.2018.00247