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 :
Recruiting
First Posted : August 16, 2018
Last Update Posted : July 8, 2020
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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
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Eosinophilic Esophagitis | Drug: Dupilumab Drug: Placebo | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 425 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 |
| Estimated Primary Completion Date : | April 22, 2022 |
| Estimated Study Completion Date : | February 24, 2023 |
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 :
- Proportion of patients achieving peak esophageal intraepithelial eosinophil count of ≤6 eosinophils per high-power field (eos/hpf) [ Time Frame: At week 24 ]
- Absolute change in Dysphagia Symptom Questionnaire (DSQ) score [ Time Frame: At 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 :
- Proportion of patients achieving peak esophageal intraepithelial eosinophil count of ≤6 eosinophils per high-power field (eos/hpf) [ Time Frame: At week 52 ]
- Absolute change in Dysphagia Symptom Questionnaire (DSQ) score [ Time Frame: At week 52 ]
- Absolute change in EoE endoscopic reference score (EREFS) [ Time Frame: At week 24 ]EoE esophageal characteristics will be analyzed based on the EoE-EREFS, a scoring system for inflammatory and remodeling features of disease using both overall scores and scores for each individual characteristic. Proximal and distal esophageal regions will be scored separately; the score for each region ranges from 0 to 9 and the overall score ranges from 0 to 18.
- Absolute change in EREFS [ Time Frame: At week 52 ]
- Percent change in peak esophageal intraepithelial eosinophil count (eos/hpf) [ Time Frame: At week 24 ]
- Percent change in peak esophageal intraepithelial eosinophil count (eos/hpf) [ Time Frame: At week 52 ]
- Absolute change in EoE Grade Score from the EoE Histology Scoring System (EoEHSS) [ Time Frame: At week 24 ]EoE 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 (absent/present). Severity (grade) and extent (stage) of abnormalities will be scored using a 4-point scale (0 normal; 3 maximum change).
- Absolute change in EoEHSS [ Time Frame: At week 52 ]
- Absolute change in EoE Stage Score from the EoEHSS [ Time Frame: At week 24 ]
- Absolute change in EoE Stage Score from the EoEHSS [ Time Frame: At week 52 ]
- Proportion of patients achieving peak esophageal intraepithelial eosinophil count of ≤15 eos/hpf [ Time Frame: At week 24 ]
- Proportion of patients achieving peak esophageal intraepithelial eosinophil count of ≤15 eos/hpf [ Time Frame: At week 52 ]
- Proportion of patients achieving peak esophageal intraepithelial eosinophil count of ≤1 eos/hpf [ Time Frame: At week 24 ]
- Proportion of patients achieving peak esophageal intraepithelial eosinophil count of ≤1 eos/hpf [ Time Frame: At week 52 ]
- Percent change in DSQ [ Time Frame: At week 24 ]
- Percent change in DSQ [ Time Frame: At week 52 ]
- Normalized Enrichment Scores (NES) for the relative change in the EoE diagnostic panel (EDP) transcriptome signature [ Time Frame: At week 24 ]NES reflects the degree to which the activity level of a set of 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 (Barbie, 2009)(Subramanian, 2005). NES scores will be calculated for each transcriptome signature for each sample for statistical analyses.
- NES for the relative change in the EDP transcriptome signature [ Time Frame: At week 52 ]
- NES for the relative change in the type 2 inflammation transcriptome signature [ Time Frame: At week 24 ]
- NES for the relative change in the type 2 inflammation transcriptome signature [ Time Frame: At week 52 ]
- Absolute change in health-related Quality of Life (QOL) as measured by EoE Impact Questionnaire (EoE-IQ) [ Time Frame: At week 24 ]The EoE-IQ is a disease-specific measure of health-related QOL in EoE patients. The EoE-IQ measures EoE impact on emotional, social, work and school, and sleep aspect of a patient.
- Absolute change in health-related QOL as measured by EoE-IQ [ Time Frame: At week 52 ]
- Absolute change in severity and/or frequency of EoE symptoms other than dysphagia [ Time Frame: At week 24 ]
- Absolute change in severity and/or frequency of EoE symptoms other than dysphagia [ Time Frame: At week 52 ]
- Portion of patients with use of rescue medications or procedures during the placebo-controlled treatment period [ Time Frame: At week 24 ]
- Portion of patients with use of rescue medications or procedures during the placebo-controlled treatment period [ Time Frame: At week 52 ]
- Absolute change in esophageal distensibility plateau measured by functional lumen imagining [ Time Frame: At week 24 ]A catheter-based procedure that measures the cross-sectional area at multiple sites along the esophagus.
- Absolute change in esophageal distensibility plateau measured by functional lumen imagining [ 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
Contacts
| Contact: Clinical Trials Administrator | 844-734-6643 | clinicaltrials@regeneron.com |
Locations
Show 81 study locations
Sponsors and Collaborators
Regeneron Pharmaceuticals
Sanofi
Investigators
| Study Director: | Clinical Trial Management | Regeneron Pharmaceuticals |
| 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 |
| Last Update Posted: | July 8, 2020 |
| Last Verified: | July 2020 |
| 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 |