Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study in Adolescents and Adults With Eosinophilic Esophagitis (EoE) Measuring Histologic Response and Determine if Reduction in Dysphagia is Achieved

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02605837
Recruitment Status : Completed
First Posted : November 16, 2015
Results First Posted : March 16, 2020
Last Update Posted : March 16, 2020
Sponsor:
Information provided by (Responsible Party):
Shire

Brief Summary:
A study in adolescents and adults with eosinophilic esophagitis (EoE) to measure the histologic response and determine if any reduction in dysphagia is achieved.

Condition or disease Intervention/treatment Phase
Eosinophilic Esophagitis (EoE) Drug: Oral Budesonide Suspension (OBS) Drug: Placebo Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 318 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Oral Budesonide Suspension (OBS) in Adolescent and Adult Subjects (11 to 55 Years of Age, Inclusive) With Eosinophilic Esophagitis: A Phase 3 Randomized, Double-blind, Placebo-controlled Study
Actual Study Start Date : December 7, 2015
Actual Primary Completion Date : January 24, 2019
Actual Study Completion Date : February 15, 2019


Arm Intervention/treatment
Experimental: Oral Budesonide Suspension (OBS)
Participants will receive Oral Budesonide Suspension (OBS) 10 milliliter (ml) of 0.2 milligram per milliliter (mg/ml) twice daily up to 16 weeks.
Drug: Oral Budesonide Suspension (OBS)
Oral Budesonide Suspension (OBS) 10 milliliter (ml) of 0.2 milligram per milliliter (mg/ml) twice daily up to 16 weeks.

Placebo Comparator: Placebo
Participants will receive oral dose of 10 ml of placebo matched with the experimental drug twice daily up to 16 weeks.
Drug: Placebo
Oral dose of 10 ml of placebo matched with the experimental drug.




Primary Outcome Measures :
  1. Number of Participants With Histologic Response at the Final Treatment Period Evaluation (Week 16) [ Time Frame: Week 16 ]
    Histologic response was defined as a peak eosinophil count of less than or equal to (<=) 6/ high-powered field (HPF) across all available esophageal levels at final treatment period evaluation (Week 16). Histologic response after 12 weeks of double blind treatment at Week 16 was reported.

  2. Number of Participants With Dysphagia Symptom Response at the Final Treatment Period Evaluation (Week 16) [ Time Frame: Week 16 ]
    Dysphagia symptom response was defined as greater than or equal to (>=) 30 percent (%) reduction in the Dysphagia Symptom Questionnaire (DSQ) combined score (questions 2+3). DSQ contained 4 questions, all participants used a diary, and responded to Questions 1 (did you eat solid food) and 2 (did food pass slowly or get stuck). If the participant's answer to Question 2 was 'No', the diary ended for that day. If a participant answered 'Yes', he/she advanced to Questions 3 (did you have to do anything to make the food go down or get relief) and 4 (extent to which the participant experienced pain while swallowing). DSQ score= ([sum of points from questions 2+3 in the daily DSQ]×14)/ Number of diaries reported with non-missing data. Dysphagia symptom response after 12 weeks of double blind treatment at Week 16 was reported.


Secondary Outcome Measures :
  1. Change From Baseline in Dysphagia Symptom Questionnaire (DSQ) Combined Score at the Final Treatment Period Evaluation (Week 16) [ Time Frame: Baseline, Week 16 ]
    DSQ contained 4 questions, all participants used a diary, and responded to Questions 1 (did you eat solid food) and 2 (did food pass slowly or get stuck). If the participant's answer to Question 2 was 'No', the diary ended for that day. If a participant answered 'Yes', he/she advanced to Questions 3 (did you have to do anything to make the food go down or get relief) and 4 (extent to which the participant experienced pain while swallowing). DSQ combined score= ([sum of points from questions 2+3 in the daily DSQ]×14)/ Number of diaries reported with non-missing data. Scale range was 0 - 2 for question 2 and 0 - 4 for question 3, with higher values representing a worse outcome. Scale range for DSQ combined score was 0 - 84, with higher values representing a worse outcome. A negative change from baseline indicates that symptoms decreased. Change from baseline in DSQ after 12 weeks of double blind treatment at Week 16 was reported.

  2. Change From Baseline in Total Endoscopy Score at the Final Treatment Period Evaluation (Week 16) [ Time Frame: Baseline, Week 16 ]
    Endoscopic findings with separate evaluations of the proximal and distal esophagus were recorded with respect to 5 categories: 1) exudates or plaques (grade 0-2); 2) fixed esophageal rings (grade 0-3); 3) edema (grade 0-2); 4) furrows (grade 0-2); and 5) strictures (grade 0-1). An endoscopy score for each category was calculated and summed for each anatomic location (proximal and distal). The minimum and maximum endoscopy score was 0 and 10 points respectively for each location (proximal and distal) and the total endoscopy score was the sum of the scores for the proximal and distal locations (maximum total score of 20 points respectively). The higher score indicated worse appearance. A negative change from baseline indicates that appearance improved. Endoscopic findings after 12 weeks of double blind treatment at Week 16 were reported.

  3. Number of Participants With Peak Eosinophil Count Less Than (<)15/High-Powered Field (HPF) or Less Than or Equal to (<=)1/High-Powered Field (HPF) at the Final Treatment Period Evaluation (Week 16) [ Time Frame: Week 16 ]
    Participant was considered as responder at Week 16 if he/she had peak eosinophil count of <15/HPF or <=1/HPF across all esophagus levels. Number of participants with peak eosinophil count < 15/HPF or <=1/HPF after 12 weeks of double blind treatment at Week 16 were reported.

  4. Change From Baseline in the Peak Eosinophil Count at the Final Treatment Period Evaluation (Week 16) [ Time Frame: Baseline, Week 16 ]
    Change from baseline in the peak eosinophil count after 12 weeks of double blind treatment at week 16 for each available esophageal level (proximal, mid, distal, maximum) were reported.

  5. Change From Baseline in the Histopathologic Epithelial Features Combined Total Score Ratio (TSR) at the Final Treatment Period Evaluation (Week 16) [ Time Frame: Baseline, Week 16 ]
    Change from baseline in histopathologic epithelial features combined total score of grade and stage ratio after 12 weeks of double blind treatment at Week 16 were reported by measuring eight histopathologic epithelial features: basal layer hyperplasia, eosinophil density, eosinophil micro-abscesses, eosinophil surface layering, dilated intercellular spaces, surface epithelial alteration, dyskeratotic epithelial cells, lamina propria fibrosis were scored on a 4-point scale (0=normal, 3=worst) for both the severity of the abnormality (grade) and the amount of tissue affected by the abnormality (stage). Thus each of the 3 levels had a minimum score of 0 and maximum possible score of 24, and a possible total grade or stage score of 72 for a maximum combined score of 144. Combined total score ratio (TSR) =(proximal TSR + mid TSR + distal TSR)/N, where N is the number of non missing sections for TSR. A negative change from baseline indicates that epithelial inflammation decreased.

  6. Number of Participants With Dysphagia Symptom Response (Binary Response) at the Final Treatment Period Evaluation (Week 16) [ Time Frame: Week 16 ]
    Dysphagia symptom response (binary response [i.e, responders versus. non-responders]) was defined as a >=50% reduction in the DSQ combined score (questions 2+3), from baseline to the final treatment period evaluation (Week 16). DSQ contained 4 questions, all participants used a diary, and responded to Questions 1 (did you eat solid food) and 2 (did food pass slowly or get stuck). If the participant's answer to Question 2 was 'No', the diary ended for that day. If a participant answered 'Yes', he/she advanced to Questions 3 (did you have to do anything to make the food go down or get relief) and 4 (extent to which the participant experienced pain while swallowing). DSQ score= ([sum of points from questions 2+3 in the daily DSQ]×14)/ Number of diaries reported with non-missing data. Number of participants with binary response after 12 weeks of double blind treatment at Week 16 were reported.

  7. Number of Participants With Overall Binary Response I at the Final Treatment Period Evaluation (Week 16) [ Time Frame: Week 16 ]
    Overall binary response I was defined as a reduction in the DSQ score of >=30% from baseline to the final treatment period (week 16) evaluation and a peak eosinophil count of <=6/HPF across all esophageal levels at the final treatment period evaluation. Participant was considered as responder at Week 16 if he/she achieved a minimum of 30% reduction in DSQ combined score between baseline and Week 16 and has peak eosinophil count of <=6/HPF across all esophagus levels. Number of participants with overall binary response I after 12 weeks of double blind treatment at Week 16 were reported.

  8. Number of Participants With Overall Binary Response II at the Final Treatment Period Evaluation (Week 16) [ Time Frame: Week 16 ]
    Overall binary response II was defined as a reduction in the DSQ score of >=50% from baseline to the final treatment period evaluation and a peak eosinophil count of <=6/HPF across all esophageal levels at the final treatment period evaluation. Participant was considered as responder at Week 16 if he/she achieved a minimum of 50% reduction in DSQ combined score between baseline and Week 16 and had peak eosinophil count of <=6/HPF across all esophagus levels. Number of participants with overall binary response II after 12 weeks of double blind treatment at Week 16 were reported.

  9. Change From Baseline in the Dysphagia Symptom Questionnaire (DSQ) + Pain Score (Questions 2 +3+4) at the Final Treatment Period Evaluation (Week 16) [ Time Frame: Baseline, Week 16 ]
    DSQ contained 4 questions, all participants used a diary, and responded to Questions 1 (did you eat solid food) and 2 (did food pass slowly or get stuck). If the participant's answer to Question 2 was 'No', the diary ended for that day. If a participant answered 'Yes', he/she advanced to Questions 3 (did you have to do anything to make the food go down or get relief) and 4 (extent to which the participant experienced pain while swallowing). DSQ + pain score was calculated by summing the scores of responses to questions 2, 3, and 4 by using following formula: DSQ + pain score= ([sum of points from questions 2+3+4 in the daily DSQ] ×14)/ Number of diaries reported with non-missing data. Scale range was 0 - 2 for question 2, 0 - 4 for question 3 and 0 - 4 for question 4, with higher values representing a worse outcome. Scale range for DSQ + pain score was 0 - 140, with higher values representing a worse outcome. A negative change from baseline indicates that symptoms decreased.

  10. Change From Baseline in the Dysphagia Symptom Questionnaire (DSQ) Pain Score (Question 4) at the Final Treatment Period Evaluation (Week 16) [ Time Frame: Baseline, Week 16 ]
    DSQ pain score was calculated by summing the scores of responses to Question 4 (extent to which the participant experienced pain while swallowing) only, by using the following formula: DSQ pain score= [(sum of points from question 4 in the daily DSQ)×14]/ Number of diaries reported with non-missing data. Scale range was 0 - 4 for question 4, with higher values representing a worse outcome. Scale range for DSQ pain score was 0 - 56, with higher values representing a worse outcome. A negative change from baseline indicates that symptoms decreased. Change from baseline in DSQ pain score (question 4) after 12 weeks of double blind treatment at Week 16 were reported.

  11. Number of Participants With Treatment-Emergent Adverse Events (AE) [ Time Frame: From start of study drug administration up to follow-up (Week 20) ]
    An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. TEAEs were defined as AEs that start or deteriorate on or after the first dose of double-blind IP (Week 44) and through the safety follow-up contact, or 31 days after the last dose of IP for participants who did not have a safety follow-up contact. Number of participants with TEAE's were reported.

  12. Area Under the Plasma Concentration-Time Curve (AUCtau) Between the Defined Interval of Budesonide Doses [ Time Frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post-dose on Week 8, 12 and 16 ]
    Area under the curve for the defined interval between doses (12 hours), calculated using the linear-up/log-down trapezoidal rule.The AUCtau of plasma budesonide was reported. Hours times pico grams per milliliter was abbreviated as h.pg/mL.

  13. Maximum Observed Concentration (Cmax) of Budesonide in Plasma [ Time Frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post-dose on Week 8, 12 and 16 ]
    The Cmax of budesonide in plasma was reported.

  14. Time to Maximum Observed Plasma Concentration (Tmax) of Budesonide in Plasma [ Time Frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post-dose on Week 8, 12 and 16 ]
    Tmax of budesonide in plasma was reported.

  15. Terminal Rate Constant (Lambda Z) of Budesonide in Plasma [ Time Frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post-dose on Week 8, 12 and 16 ]
    Lambda Z of budesonide in plasma was reported.

  16. Terminal Half-Life (t1/2) of Budesonide in Plasma [ Time Frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post-dose on Week 8, 12 and 16 ]
    t1/2 of budesonide in plasma was reported

  17. Apparent Oral Clearance (CL/F) of Budesonide in Plasma [ Time Frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post-dose on Week 8, 12 and 16 ]
    CL/F of budesonide in plasma was reported.

  18. Apparent Volume of Distribution (Vz/F) of Budesonide in Plasma [ Time Frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, and 12 hours post-dose on Week 8, 12 and 16 ]
    Vz/F of budesonide in plasma was reported.



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.


Layout table for eligibility information
Ages Eligible for Study:   11 Years to 55 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • Participants is able to provide written informed consent (participant, parent or legal guardian, and, as appropriate, participant assent) to participate in the study before completing any study-related procedures.
  • Participant is male or female aged 11-55 years, inclusive, at time of consent.
  • Participant has histologic evidence of eosinophilic esophagitis (EoE) with a peak eosinophil count of greater than or equal to (>=) 15/ high-powered field (HPF), from 2 of 3 (proximal, mid-, and/or distal) levels of the esophagus at the screening endoscopy.
  • Participant has a history of clinical symptoms of esophageal dysfunction (for example, eating problems, abdominal pain, heartburn, dysphagia, vomiting, food impaction, weight loss) intermittently or continuously at screening (Visit -1).
  • Participants must have experienced dysphagia (response of "yes" to question 2 on Dysphagia Symptom Questionnaire [DSQ]) on a minimum of 4 days and completed the DSQ on >= 70 percent (%) of days in any 2 consecutive weeks of the screening period and in the last 2 weeks prior to the baseline visit (Visit 1).
  • Participant must not have PPI-responsive EoE based on esophageal biopsies performed after the patient has been on at least 8 weeks of high-dose PPI therapy (high-dose therapy refers to the total daily dose, which may have been administered as a once or twice daily dosing regimen). This may occur at the time of the qualifying esophagogastroduodenoscopy (EGD) (in which case the same proton pump inhibitor (PPI) regimen must be continued), or this may have been done previously (in which case PPI therapy may have been stopped if there was no response to therapy based on esophageal biopsy results). If PPI responsiveness was excluded by a previous EGD and biopsy, the historical EGD and biopsy must have been performed after the patient had been on a minimum of 6 weeks of high-dose PPI therapy.
  • Participant will be on a stable (no changes) diet >=3 months prior to the screening visit (Visit -1).
  • Participant is willing and able to continue any dietary therapy, environmental therapy, and/or medical regimens (including gastric acid suppression) in effect at the screening visit (Visit -1). There should be no change to these regimens during study participation.
  • All female participants must have a negative serum pregnancy test (beta-human chorionic gonadotropin [β-hCG]) prior to enrollment into the study. Females of childbearing potential must agree to continue acceptable birth control measures (for example, abstinence, stable oral contraceptives, or double-barrier methods) throughout study participation.
  • Participant is willing and has an understanding and ability to fully comply with study procedures and restrictions defined in this protocol.

Exclusion Criteria

  • Participant has any condition or abnormality (including laboratory abnormalities), current or past, that, in the opinion of the principal investigator or medical monitor, would compromise the safety of the participant or interfere with or complicate the assessment of signs or symptoms of EoE. Such conditions may include psychiatric problems; neurologic deficits or disease; developmental delay; cardiovascular, metabolic, or pulmonary disease; or previous gastroesophageal surgery. These should be discussed with the medical monitor.
  • Participant has used immunomodulatory therapy within 8 weeks prior to the qualifying EGD or between the qualifying EGD and baseline visit (Visit 1) or anticipates using immunomodulatory therapy during the treatment period (except for any ongoing regimen of allergy shots). Use of long-acting immunomodulatory therapy (for example, Rituxan) within 3 months of the qualifying EGD should be reviewed with the medical monitor.
  • Participant has been using swallowed topical corticosteroid for EoE or systemic corticosteroid for any condition within the 4 weeks prior to the qualifying EGD, between the qualifying EGD and baseline visit (Visit 1), or anticipates use during the treatment period; any temporary use (less than or equal to [<=]7 days) or initiation of new steroid treatment during the study should be documented and discussed with the medical monitor prospectively but cannot occur within 4 weeks of the final EGD.
  • Participant has been on inhaled steroids and has not been on stable treatment for >=3 months prior to screening visit (Visit -1). Participants on inhaled steroids need to stay on a stable treatment during study participation. Participant has been on intranasal steroids and has not been on stable treatment for a minimum of 4 weeks prior to the qualifying EGD. After the qualifying EGD, participants with seasonal allergic rhinitis may resume (or discontinue) intranasal corticosteroids based on the participant's usual treatment regimen for allergy season.
  • Participant has initiated, discontinued, or changed dosage regimen of PPIs, H2 antagonists, antacids, or leukotriene inhibitors for any condition (such as gastroesophageal reflux disease, asthma or allergic rhinitis) within the 4 weeks prior to the qualifying EGD, between the qualifying EGD and baseline visit (Visit 1), or anticipates changes in the use of such medications during the treatment period.
  • Participant has been using cytochrome P450 3A4 (CYP450 3A4) inhibitors (for example, ketoconazole, grapefruit juice) within the 2 weeks prior to the baseline visit (Visit 1) or within 5 half-lives (whichever is greater) or anticipates using such medications during the treatment period.
  • Participant has an appearance on qualifying EGD of an esophageal stricture (high-grade), as defined by the presence of a lesion that does not allow passage of a diagnostic adult upper endoscope (for example, with an insertion tube diameter of greater than [>]9 millimeter [mm]).
  • Participant is on a pure liquid diet or the 6-food elimination diet.
  • Participant has had an esophageal dilation within the 3 months prior to screening (Visit -1).
  • Participant has presence of esophageal varices at the screening endoscopy.
  • Participant has any current disease of the gastrointestinal tract, aside from EoE, including eosinophilic gastritis, enteritis, colitis, or proctitis; inflammatory bowel disease; or celiac disease.
  • Participant has other diseases causing or associated with EoE, including hypereosinophilic syndrome, collagen vascular disease, vasculitis, achalasia, or parasitic infection.
  • Participant has current evidence of oropharyngeal or esophageal candidiasis.
  • Participant has a potentially serious acute or chronic viral infection or immunodeficiency condition, including tuberculosis, fungal, bacterial, viral/parasite infection, ocular herpes simplex, herpes esophagitis, or chicken pox/measles.
  • Participant has upper gastrointestinal bleeding within 4 weeks prior to the screening visit (Visit - 1) or between the screening visit and baseline visit (Visit 1).
  • Participant has evidence of active infection with Helicobacter pylori.
  • Participant has evidence of unstable asthma within 4 weeks prior to the screening visit (Visit -1) and between the screening visit and baseline visit (Visit 1).
  • Participant is female and pregnant or nursing.
  • Participant has a history of intolerance, hypersensitivity, or idiosyncratic reaction to budesonide (or any other corticosteroids) or to any other ingredients of the investigational product.
  • Participant has taken part and received intervention in an interventional study related to EoE (except for an interventional study for a topical swallowed steroid) within 6 months prior to the screening visit (Visit -1), or any investigational study within 30 days prior to the screening visit (Visit -1). An investigational topical swallowed steroid must have been discontinued at least 30 days prior to the screening visit (Visit -1).
  • Participant has a history or high risk of noncompliance with treatment or regular clinic visits.
  • Participant has previously completed, discontinued, or withdrawn from this study.
  • Participant has participated in a previous clinical study involving oral budesonide suspension (OBS) (SHP621).
  • Participant anticipates using sucralfate during the study.

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): NCT02605837


Locations
Show Show 77 study locations
Sponsors and Collaborators
Shire
Investigators
Layout table for investigator information
Study Director: Study Director Shire
  Study Documents (Full-Text)

Documents provided by Shire:
Study Protocol  [PDF] January 26, 2018
Statistical Analysis Plan  [PDF] March 11, 2019

Layout table for additonal information
Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT02605837    
Other Study ID Numbers: SHP621-301
First Posted: November 16, 2015    Key Record Dates
Results First Posted: March 16, 2020
Last Update Posted: March 16, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Shire provides access to the de-identified individual participant data for eligible studies to aid qualified researchers in addressing legitimate scientific objectives. These IPDs will be provided following approval of a data sharing request, and under the terms of a data sharing agreement.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.shiretrials.com website. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
URL: https://www.shiretrials.com/en/our-commitment-to-transparency/data-sharing-with-researchers
Additional relevant MeSH terms:
Layout table for MeSH terms
Esophagitis
Eosinophilic Esophagitis
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Gastroenteritis
Eosinophilia
Leukocyte Disorders
Hematologic Diseases
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Budesonide
Anti-Inflammatory Agents
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists