Trial record 1 of 1 for:
NCT03633617
Study to Determine the Efficacy and Safety of Dupilumab in Adult and Adolescent Patients With Eosinophilic Esophagitis (EoE)
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| ClinicalTrials.gov Identifier: NCT03633617 |
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Recruitment Status :
Completed
First Posted : August 16, 2018
Results First Posted : December 28, 2022
Last Update Posted : December 28, 2022
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Sponsor:
Regeneron Pharmaceuticals
Collaborator:
Sanofi
Information provided by (Responsible Party):
Regeneron Pharmaceuticals
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Brief Summary:
The primary objectives of the study by study part are:
Part A:
To determine the treatment effect of dupilumab compared with placebo in adult and adolescent patients with EoE after 24 weeks of treatment as assessed by histological and clinical measures and to inform/confirm the final sample size determination for Part B.
Part B:
To demonstrate the efficacy of dupilumab treatment compared with placebo in adult and adolescent patients with EoE after 24 weeks of treatment as assessed by histological and clinical measures.
Part C:
To assess the safety and efficacy of dupilumab treatment in adult and adolescent patients with EoE after up to 52 weeks of treatment as assessed by histological and clinical measures.
The secondary objectives of the study are:
- To evaluate the safety, tolerability, and immunogenicity of dupilumab treatment for up to 52 weeks in adult and adolescent patients with EoE
- To explore the relationship between dupilumab concentration and responses in adult and adolescent patients with EoE, using descriptive analyses
- To evaluate the effects of dupilumab on transcriptomic signatures associated with EoE and type 2 inflammation
- To demonstrate the efficacy of dupilumab treatment compared to placebo after 24 weeks and 52 weeks of treatment in adult and adolescent patients with EoE who have previously received swallowed topical corticosteroids
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Eosinophilic Esophagitis | Drug: Dupilumab Drug: Placebo | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 321 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 3, Randomized, 3-Part Study to Investigate the Efficacy and Safety of Dupilumab in Adult and Adolescent Patients With Eosinophilic Esophagitis (EoE) |
| Actual Study Start Date : | September 24, 2018 |
| Actual Primary Completion Date : | September 9, 2021 |
| Actual Study Completion Date : | June 7, 2022 |
Resource links provided by the National Library of Medicine
MedlinePlus related topics:
Eosinophilic Esophagitis
Drug Information available for:
Dupilumab
| Arm | Intervention/treatment |
|---|---|
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Experimental: Part A: Dupilumab or Placebo
Part A consists of a 24-week double-blind treatment period. Participants will be randomized to receive dupilumab or placebo. At the end of the double-blind treatment visit (week 24), eligible participants may enter Part C. Participants who do not enter Part C will enter a 12-week follow-up period.
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Drug: Dupilumab
Solution for injection administered subcutaneously
Other Names:
Drug: Placebo Matching placebo |
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Experimental: Part B: Dupilumab or Placebo
Part B consists of a 24-week double-blind treatment period. Participants will be randomized to receive dupilumab dosing regimen 1, dupilumab dosing regimen 2 or placebo. At the end of the double-blind treatment visit (week 24), eligible participants may enter Part C. Participants who do not enter Part C will enter a 12-week follow-up period.
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Drug: Dupilumab
Solution for injection administered subcutaneously
Other Names:
Drug: Placebo Matching placebo |
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Experimental: Part C: Dupilumab
Part C is a 28-week extended active treatment period. Participants will receive dupilumab dosing regimen 1, dupilumab dosing regimen 2. At the end of the treatment period (week 52), participants will enter a 12-week follow-up period.
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Drug: Dupilumab
Solution for injection administered subcutaneously
Other Names:
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Primary Outcome Measures :
- Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤6 Eosinophils Per High-power Field (Eos/Hpf) in All Three Regions at Week 24 [ Time Frame: At week 24 ]Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies (all 3 esophageal regions: proximal, mid, and distal).
- Absolute Change From Baseline in Dysphagia Symptom Questionnaire (DSQ) Total Score at Week 24 [ Time Frame: Baseline and week 24 ]The DSQ is used to measure the frequency and intensity of dysphagia. DSQ scores can range from 0 to 84, with a lower score indicating less-frequent or less-severe dysphagia.
Secondary Outcome Measures :
- Percent Change From Baseline in DSQ Total Score at Week 24 [ Time Frame: Baseline and week 24 ]The DSQ is used to measure the frequency and intensity of dysphagia. DSQ scores can range from 0 to 84, with a lower score indicating less-frequent or less-severe dysphagia.
- Percent Change From Baseline in Peak Esophageal Intraepithelial Eosinophil Count at Week 24 [ Time Frame: Baseline and week 24 ]Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies (all 3 esophageal regions: proximal, mid, and distal). A greater esophageal intraepithelial eosinophil count from baseline indicates worsening disease.
- Absolute Change From Baseline in Eosinophilic Esophagitis (EoE) Grade Score From the EoE Histology Scoring System (EoEHSS) at Week 24 [ Time Frame: Baseline and week 24 ]Severity (grade) and extent (stage) of esophageal abnormalities were scored by blinded, central pathologists using a 4-point scale (0 normal; 3 maximum change) for 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 (absent/present). Higher score indicates greater severity and extent of histological abnormalities.
- Absolute Change From Baseline in EoE Stage Score From the EoEHSS at Week 24 [ Time Frame: Baseline and week 24 ]Severity (grade) and extent (stage) of esophageal abnormalities were scored by blinded, central pathologists using a 4-point scale (0 normal; 3 maximum change) for 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 (absent/present). Higher score indicates greater severity and extent of histological abnormalities.
- Absolute Change From Baseline in Eosinophilic Esophagitis Endoscopic Reference (EoE-EREFS) Total Score at Week 24 [ Time Frame: Baseline and week 24 ]EoE esophageal characteristics analyzed based on the EoE-EREFS, a scoring system for inflammatory and remodeling features of disease. The overall total score ranges from 0 to 18 with higher number indicating worse disease.
- Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eos/Hpf in All Three Regions at Week 24 [ Time Frame: At week 24 ]Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies (all 3 esophageal regions: proximal, mid, and distal).
- Normalized Enrichment Score (NES) for the Relative Change From Baseline in the EoE Diagnostic Panel (EDP) at Week 24 [ Time Frame: Baseline and week 24 ]NES reflects the degree to which the activity level of a set of disease transcripts is overrepresented at the extremes (top or bottom) of the entire ranked list of transcripts within a sample and is normalized by accounting for the number of transcripts in the set. An NES of 0 indicates no change from baseline, a negative score reflects a reduction in the disease score (more like normal) and a positive score reflects worsening (more active disease).
- Normalized Enrichment Score (NES) for the Relative Change From Baseline in the Type 2 Inflammation Signature (T2INF) at Week 24 [ Time Frame: Baseline and week 24 ]NES reflects the degree to which the activity level of a set of disease transcripts is overrepresented at the extremes (top or bottom) of the entire ranked list of transcripts within a sample and is normalized by accounting for the number of transcripts in the set. An NES of 0 indicates no change from baseline, a negative score reflects a reduction in the disease score (more like normal) and a positive score reflects worsening (more active disease).
- Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤1 Eos/Hpf in All Three Regions at Week 24 [ Time Frame: At week 24 ]Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies (all 3 esophageal regions: proximal, mid, and distal).
- Absolute Change From Baseline in Health-related Quality of Life (QoL) Average Score as Measured by Eosinophilic Esophagitis Impact Questionnaire (EoE-IQ) at Week 24 [ Time Frame: Baseline and week 24 ]The EoE-IQ measures impact of EoE on emotional, social, work & school, & sleep aspects. Participants were asked to respond to 11 questions based on experience living with EoE during past 7 days. Response to each item is on a 5-point scale (1=Not at all [impacted] 2=A little, 3=Somewhat, 4=Quite a bit, 5=Extremely [impacted]). The average score is the sum of non-missing responses divided by the number of items with non-missing responses. The average score can range from 1 to 5; a higher score is indicative of a more negative impact.
- Absolute Change From Baseline in Severity of EoE Symptoms Other Than Dysphagia as Measured by EoE Symptom Questionnaire (EoE-SQ) at Week 24 [ Time Frame: Baseline and week 24 ]The EoE-SQ asks about symptoms that participants with EoE may have (chest pain, stomach pain, burning feeling in chest, food or liquid coming back up into throat, throwing up) during the past 7 days. Response to the severity of each symptom based on the worst experience in the past 7 days is on a scale of 0 to 10 (higher is worse). The EoE-SQ severity score is calculated as the sum of the severity scores from questions 1 to 3 (chest pain, stomach pain, burning feeling in chest), which could range from 0 to 30; a higher score is indicative of more severe symptoms.
- Absolute Change From Baseline in Frequency of EoE Symptoms Other Than Dysphagia as Measured by EoE Symptom Questionnaire (EoE-SQ) at Week 24 [ Time Frame: Baseline and week 24 ]The EoE-SQ asks about symptoms that participants with EoE may have (chest pain, stomach pain, burning feeling in chest, food or liquid coming back up into throat, throwing up) during the past 7 days. Response to the frequency of each symptom is on a 5-point scale (1 = 'Never', 2 = 'One day', 3 = ' 2-6 days', 4 = 'Once a day', 5 = 'More than once a day'). The EoE-SQ frequency score is calculated as the sum of the frequency scores from the 5 items which could range from 5 to 25; a higher score is indicative of higher frequency of symptoms.
- Percentage of Participants Who Received Rescue Treatment During the Placebo-controlled, Double-blind Treatment Period at Week 24 [ Time Frame: At week 24 ]
- Absolute Change From Baseline in Esophageal Distensibility Plateau Measured by Functional Lumen Imaging, if Collected, at Week 24 [ Time Frame: At week 24 ]
- Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤6 Eosinophils Per High-power Field (Eos/Hpf) at Week 52 [ Time Frame: At week 52 ]
- Absolute Change in Dysphagia Symptom Questionnaire (DSQ) Score at Week 52 [ Time Frame: At week 52 ]
- Absolute Change in EREFS at Week 52 [ Time Frame: At week 52 ]
- Percent Change in Peak Esophageal Intraepithelial Eosinophil Count (Eos/Hpf) at Week 52 [ Time Frame: At week 52 ]
- Absolute Change in EoEHSS at Week 52 [ Time Frame: At week 52 ]
- Absolute Change in EoE Stage Score From the EoEHSS at Week 52 [ Time Frame: At week 52 ]
- Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤15 Eos/Hpf at Week 52 [ Time Frame: At week 52 ]
- Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤1 Eos/Hpf at Week 52 [ Time Frame: At week 52 ]
- Percent Change in DSQ at Week 52 [ Time Frame: At week 52 ]
- NES for the Relative Change in the EDP Transcriptome Signature at Week 52 [ Time Frame: At week 52 ]
- NES for the Relative Change in the Type 2 Inflammation Transcriptome Signature at Week 52 [ Time Frame: At week 52 ]
- Absolute Change in Health-related QOL as Measured by EoE-IQ at Week 52 [ Time Frame: At week 52 ]
- Absolute Change in Severity and/or Frequency of EoE Symptoms Other Than Dysphagia at Week 52 [ Time Frame: At week 52 ]
- Percentage of Participants With Use of Rescue Medications or Procedures During the Placebo-controlled Treatment Period at Week 52 [ Time Frame: At week 52 ]
- Concentration of Functional Dupilumab in Serum [ Time Frame: Up to week 52 ]
- Incidence of Treatment-emergent Anti-drug Antibody (ADA) Responses and Titer [ Time Frame: Up to week 52 ]
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 12 Years and older (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Key Inclusion Criteria (Parts A & B):
- A documented diagnosis of EoE by endoscopic biopsy
- Baseline endoscopic biopsies with a demonstration on central reading of intraepithelial eosinophilic infiltration
- History (by patient report) of an average of at least 2 episodes of dysphagia (with intake of solids) per week in the 4 weeks prior to screening
Key Exclusion Criteria (Parts A & B):
- Body weight ≤40 kg
- Prior participation in a dupilumab clinical trial, or past or current treatment with dupilumab
- Initiation or change of a food-elimination diet regimen or re-introduction of a previously eliminated food group in the 6 weeks prior to screening.
- Other causes of esophageal eosinophilia or the following conditions: hypereosinophilic syndrome and eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)
- Active Helicobacter pylori infection
- History of achalasia, Crohn's disease, ulcerative colitis, celiac disease, and prior esophageal surgery
- Any esophageal stricture unable to be passed with a standard, diagnostic, 9 to10 mm upper endoscope or any critical esophageal stricture that requires dilation at screening
- History of bleeding disorders or esophageal varices
- Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study
Key Exclusion Criteria (Part C):
- Participants who, during Part A or Part B, developed a serious adverse event (SAE) and/or adverse event (AE) deemed related to study drug, which in the opinion of the investigator could indicate that continued treatment with study drug may present an unreasonable risk for the participant
- Participants who became pregnant during Part A or Part B
- Participants who are prematurely discontinued from study drug due to an AE (patients who are prematurely discontinued from study drug due to lack of efficacy are eligible to enter Part C)
- Patients who did not undergo endoscopy with biopsies prior to receiving rescue treatment
Note: Other inclusion/ exclusion criteria apply
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03633617
Locations
Show 95 study locations
Sponsors and Collaborators
Regeneron Pharmaceuticals
Sanofi
Investigators
| Study Director: | Clinical Trial Management | Regeneron Pharmaceuticals |
Study Documents (Full-Text)
Documents provided by Regeneron Pharmaceuticals:
Documents provided by Regeneron Pharmaceuticals:
Study Protocol [PDF] November 5, 2020
Statistical Analysis Plan: Part A/Part C [PDF] April 24, 2020
Statistical Analysis Plan: Part B/Part C [PDF] September 21, 2021
| Responsible Party: | Regeneron Pharmaceuticals |
| ClinicalTrials.gov Identifier: | NCT03633617 |
| Other Study ID Numbers: |
R668-EE-1774 2018-000844-25 ( EudraCT Number ) |
| First Posted: | August 16, 2018 Key Record Dates |
| Results First Posted: | December 28, 2022 |
| Last Update Posted: | December 28, 2022 |
| Last Verified: | December 2022 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Esophagitis Eosinophilic Esophagitis Esophageal Diseases Gastrointestinal Diseases Digestive System Diseases Gastroenteritis |
Eosinophilia Leukocyte Disorders Hematologic Diseases Hypersensitivity, Immediate Hypersensitivity Immune System Diseases |