Continuation Study With Budesonide Oral Suspension (BOS) for Adolescent and Adult Participants With Eosinophilic Esophagitis (EoE)

Study Overview
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Brief Summary
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This is a continuation study of Budesonide Oral Suspension (BOS) in adults and adolescents with Eosinophilic Esophagitis (EoE) who have completed participation in the SHP621-302 extension study. The purpose of this study is to see if BOS is safe and well tolerated over the long-term in adolescents and adults with EoE.

Official Title
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A Phase 3, Multicenter, Open-label Continuation Study With Budesonide Oral Suspension (BOS) for Adolescent and Adult Subjects With Eosinophilic Esophagitis (EoE)

Conditions
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Eosinophilic Esophagitis (EoE)

Intervention / Treatment
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* Drug: Budesonide oral suspension


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant completed the SHP621-302 (NCT02736409) extension study and is considered by the investigator to potentially benefit from continued BOS investigational treatment. Participant 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. Females of childbearing potential must agree to continue acceptable birth control measures (example (e.g.): abstinence, surgically sterile male partner, 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 as defined in protocol. Exclusion Criteria: Participant has changes in medications or diet during the SHP621-302 (NCT02736409) study that could affect participation in this continuation study. Participant anticipates using swallowed topical corticosteroid for EoE or systemic corticosteroid for any condition 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 should be avoided within 4 weeks of the scheduled esophagogastroduodenoscopy (EGDs). Participant anticipates use of Cytochrome P450 3A4 inhibitors (e.g., ketoconazole, grapefruit juice) during the continuation study. Participant has an appearance at the EGD at the final treatment evaluation visit of SHP621-302 (NCT02736409) (Visit 8) 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 (e.g., with an insertion tube diameter of greater than (>) 9 millimeter [mm]). Participant has presence of esophageal varices at the EGD at the final treatment evaluation visit (Visit 8) of the SHP621-302 (NCT02736409) study. 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 esophageal eosinophilia, including hypereosinophilic syndrome, collagen vascular disease, vasculitis, achalasia, or parasitic infection. Participant has oropharyngeal or esophageal candidiasis that failed to respond to previous treatment. Diagnosis with oropharyngeal or esophageal candidiasis at or since the final treatment evaluation visit (Visit 8) of the SHP621-302 (NCT02736409) study is not an exclusion as long as the participant is expected to respond to treatment. Participant has a potentially serious acute or chronic infection or immunodeficiency condition, including tuberculosis, fungal, bacterial, viral/parasite infection, ocular herpes simplex, or chicken pox/measles. Participant has upper gastrointestinal bleeding identified at the EGD at the final treatment evaluation visit (Visit 8) of the SHP621-302 (NCT02736409) study. Participant has evidence of active infection with Helicobacter pylori. Participant has evidence of unstable asthma. 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 study medication. Participant has a history or high risk of noncompliance with treatment or regular clinic visits.

Ages Eligible for Study
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Minimum Age: 11 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Budesonide Oral Suspension<br>Participants received 10 milliliters (mL) of budesonide oral suspension at a concentration of 0.2 milligram per milliliter (mg/mL), twice daily, for up to 4 years 5 months. | Drug: Budesonide oral suspension<br>* BOS 10 mL twice daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | An adverse event (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. A Serious Adverse Event (SAE) was any untoward medical occurrence (whether considered to be related to investigational product or not) that at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital abnormality/birth defect, and is an important medical event. Both serious and Non-serious TEAEs were reported in this outcome measure. TEAEs were defined as AEs with a start date on or after the first dose of investigational product or a start date before the date of the first dose of investigational product that increased in severity or after the date of the first dose. | From start of study drug administration up to End of study (EOS) (Up to Month 53) | 
| Number of Participants With Clinically Significant Physical Examination Findings | Number of participants with clinically significant physical examination findings were reported. Clinical significance was determined by investigator. | From start of study drug administration up to EOS (Up to Month 53) | 
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs | Participants were assessed by investigator for any clinically significant changes in vital parameters like temperature, systolic and diastolic blood pressure, pulse, respiratory rate, BMI, and weight. Vital signs were assessed after the participant had been in a supine position for at least 5 minutes immediately prior to the assessment. The criteria for clinically significant change was as per the investigators discretion. | From start of study drug administration up to EOS (Up to Month 53) | 
| Change From Baseline in Bone Mineral Density (BMD) For Adolescents Assessed by Dual-Energy X-ray Absorptiometry (DXA) Scan at Month 12 | The sites for DXA measurement were the lumbar spine at lumbar vertebrae 1 to 4 (L1-L4) and whole body. DXA scans for determination of BMD and body composition was performed in participants aged 11-17 years. Z-score indicates the number of standard deviations away from a reference population in the same age range and with the same sex. In this study, the BMD Z-score is considered abnormal when the z-score is less than (<) -2, suggesting a worse outcome (i.e., osteoporosis). Change from baseline in BMD for adolescents assessed by DXA Scan at Month 12 was reported. | Baseline, Month 12 | 
| Change From Baseline in BMD For Adolescents Assessed by DXA Scan at Month 24 | The sites for DXA measurement were the lumbar spine at lumbar vertebrae 1 to 4 (L1-L4) and whole body. DXA scans for determination of BMD and body composition was performed in participants aged 11-17 years. Z-score indicates the number of standard deviations away from a reference population in the same age range and with the same sex. In this study, the BMD Z-score is considered abnormal when the z-score is <-2, suggesting a worse outcome (i.e., osteoporosis) and vice versa. Change from baseline in BMD for adolescents assessed by DXA Scan at Month 24 was reported. | Baseline, Month 24 | 
| Change From Baseline in BMD For Adolescents Assessed by DXA Scan at Month 36 | The sites for DXA measurement were the lumbar spine at lumbar vertebrae 1 to 4 (L1-L4) and whole body. DXA scans for determination of BMD and body composition was performed in participants aged 11-17 years. Z-score indicates the number of standard deviations away from a reference population in the same age range and with the same sex. In this study, the BMD Z-score is considered abnormal when the z-score is < -2, suggesting a worse outcome (i.e., osteoporosis) and vice versa. Change from baseline in BMD for adolescents assessed by DXA Scan at Month 36 was reported. | Baseline, Month 36 | 
| Change From Baseline in BMD For Adolescents Assessed by DXA Scan at Month 48 | The sites for DXA measurement were the lumbar spine at lumbar vertebrae 1 to 4 (L1-L4) and whole body. DXA scans for determination of BMD and body composition was performed in participants aged 11-17 years. Z-score indicates the number of standard deviations away from a reference population in the same age range and with the same sex. In this study, the BMD Z-score is considered abnormal when the z-score is < -2, suggesting a worse outcome (i.e., osteoporosis) and vice versa. Change from baseline in BMD for adolescents assessed by DXA Scan at Month 48 was reported. | Baseline, Month 48 | 
| Change From Baseline in BMD For Adolescents Assessed by DXA Scan at EOS (Up to Month 53) | The sites for DXA measurement were the lumbar spine at lumbar vertebrae 1 to 4 (L1-L4) and whole body. DXA scans for determination of BMD and body composition was performed in participants aged 11-17 years. Z-score indicates the number of standard deviations away from a reference population in the same age range and with the same sex. In this study, the BMD Z-score is considered abnormal when the z-score is < -2, suggesting a worse outcome (i.e., osteoporosis) and vice versa. Change from baseline in BMD for adolescents assessed by DXA Scan at EOS (up to Month 53) was reported. | Baseline, EOS (Up to Month 53) | 
| Change From Baseline in Cortisol Level After Adrenocorticotropic Hormone (ACTH) Stimulation at Month 12 | ACTH testing was a standard procedure to measure the levels of cortisol in the blood following the injection of a synthetic form of ACTH (250 microgram [mcg]). The type of synthetic and route of administration was per investigator discretion. The change from baseline in cortisol levels was calculated at Month 12 and reported in this outcome measure. | Baseline, Month 12 | 
| Change From Baseline in Cortisol Level After ACTH Stimulation at Month 24 | ACTH testing was a standard procedure to measure the levels of cortisol in the blood following the injection of a synthetic form of ACTH (250 microgram [mcg]). The type of synthetic and route of administration was per investigator discretion. The change from baseline in cortisol levels was calculated at Month 24 and reported in this outcome measure. | Baseline, Month 24 | 
| Change From Baseline in Cortisol Level After ACTH Stimulation at Month 36 | ACTH testing was a standard procedure to measure the levels of cortisol in the blood following the injection of a synthetic form of ACTH (250 microgram [mcg]). The type of synthetic and route of administration was per investigator discretion. The change from baseline in cortisol levels was calculated at Month 36 and reported in this outcome measure. | Baseline, Month 36 | 
| Change From Baseline in Cortisol Level After ACTH Stimulation at Month 48 | ACTH testing was a standard procedure to measure the levels of cortisol in the blood following the injection of a synthetic form of ACTH (250 microgram [mcg]). The type of synthetic and route of administration was per investigator discretion. The change from baseline in cortisol levels was calculated at Month 48 and reported in this outcome measure. | Baseline, Month 48 | 
| Change From Baseline in Cortisol Level After ACTH Stimulation at EOS (Up to Month 53) | ACTH testing was a standard procedure to measure the levels of cortisol in the blood following the injection of a synthetic form of ACTH (250 microgram [mcg]). The type of synthetic and route of administration was per investigator discretion. The change from baseline in cortisol levels was calculated at EOS (up to Month 53) and reported in this outcome measure. | Baseline, EOS (Up to Month 53) | 
| Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessments | Clinical laboratory parameters included hematology, chemistry, urinalysis; urine pregnancy test. Number of participants with potential clinically significant changes in laboratory parameters which were deemed clinically meaningful by the investigator were reported. | From start of study drug administration up to EOS (Up to Month 53) |