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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00358449




Registration number
NCT00358449
Ethics application status
Date submitted
27/07/2006
Date registered
31/07/2006

Titles & IDs
Public title
Intravenous Mepolizumab In Children With Eosinophilic Esophagitis
Scientific title
A Randomized, Double-blind, Parallel Group Clinical Trial to Assess Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intravenous Mepolizumab (SB240563)(0.55mg/kg, 2.5mg/kg or 10mg/kg) in Pediatric Subjects With Eosinophilic Esophagitis, Aged 2 to 17 Years (Study MEE103219)
Secondary ID [1] 0 0
MEE103219
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Oesophagitis, Eosinophilic 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Inflammatory and Immune System 0 0 0 0
Allergies

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - mepolizumab

Experimental: Mepolizumab 0.55 mg/kg - Participants received mepolizumab 0.55 milligrams (mg)/kilogram (kg) by intravenous (IV) infusion for 30 minutes on Day 1, Week 4 and Week 8.

Experimental: Mepolizumab 2.5 mg/kg - Participants received mepolizumab 2.5 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.

Experimental: Mepolizumab 10 mg/kg - Participants received mepolizumab 10 mg/kg by IV infusion for 30 minutes on Day 1, Week 4 and Week 8.


Treatment: Drugs: mepolizumab
Participants received mepolizumab 0.55 milligrams (mg)/kilogram (kg), 2.5 mg/kg , or 10 mg/kg by intravenous (IV) infusion for 30 minutes on Day 1, Week 4 and Week 8.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Any Adverse Events (AE), Any Serious Adverse Event (SAE) and Drug-related AE During Treatment Phase (TP) and Follow-up Phase (FP)
Timepoint [1] 0 0
From first dose of study treatment (Day 1) up to Follow-up Phase (Week 24)
Primary outcome [2] 0 0
Number of Participants With Indicated Biochemistry Parameters Falling Outside of Reference Range (RR) in Any Vist Post-Basline During Study Period.
Timepoint [2] 0 0
From first dose of study treatment (Day 1) up to Follow-up Phase (Week 24)
Primary outcome [3] 0 0
Number of Participants With Indicated Hematology Parameters Falling Outside of Reference Range (RR) in Any Vist Post-Basline During the Study Period.
Timepoint [3] 0 0
From first dose of study treatment (Day 1) up to Long-term Follow-up Phase (Week 34)
Primary outcome [4] 0 0
Number of Participants With the Indicated Change From Baseline in ECG Findings at Any Time Post-Baseline
Timepoint [4] 0 0
Screening, Weeks 4, 8 and 12
Primary outcome [5] 0 0
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Indicated Time Points
Timepoint [5] 0 0
Screening, Day 1, Weeks 4, 8, 12, 16, 20, and 24
Primary outcome [6] 0 0
Change From Baseline in Heart Rate at the Indicated Time Points
Timepoint [6] 0 0
Screening, Day 1, Weeks 4, 8, 12, 16, 20, and 24
Primary outcome [7] 0 0
Change From Baseline in Temperature at the Indicated Time Points
Timepoint [7] 0 0
Screening, Day 1, Weeks 4, 8, 12, 16, 20 and 24
Primary outcome [8] 0 0
Number of Participants With Positive and Negative Anti-mepolizumab Antibody Results at Any Visit and Repeat Visit.
Timepoint [8] 0 0
Day 1, Weeks 4, 8, 12, 24, and 34
Primary outcome [9] 0 0
Number of Participants Achieving a Reduction in Peak Esophageal Eosinophil Count to < 5 Cells Per High Power Field (HPF) at Week 12
Timepoint [9] 0 0
Week 12
Primary outcome [10] 0 0
Central (V1), Periperial (V2) and Steady-State (Vss) Volume of Distribution of Mepolizumab
Timepoint [10] 0 0
Day 1, Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, and 34
Primary outcome [11] 0 0
Plasma Clearance (CL) of Mepolizumab
Timepoint [11] 0 0
Day 1, Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, and 34
Secondary outcome [1] 0 0
Change From Baseline in Pain in Stomach Severity Scores
Timepoint [1] 0 0
Screening, Weeks 9-12 and Weeks 21-24
Secondary outcome [2] 0 0
Change From Baseline in Pain in Chest/Throat Severity Scores
Timepoint [2] 0 0
Screening, Weeks 9-12 and Weeks 21-24
Secondary outcome [3] 0 0
Change From Baseline in Percentage of Days With Pain in Stomach
Timepoint [3] 0 0
Screening, Weeks 9-12 and Weeks 21-24
Secondary outcome [4] 0 0
Change From Baseline in Percentage of Days With Pain in Chest/Throat
Timepoint [4] 0 0
Screening, Weeks 9-12 and Weeks 21-24
Secondary outcome [5] 0 0
Change From Baseline in Regurgitation Bothersome Scores
Timepoint [5] 0 0
Screening, Weeks 9-12 and Weeks 21-24
Secondary outcome [6] 0 0
Change From Baseline in Percentage of Days With Regurgitation Bothersome Scores
Timepoint [6] 0 0
Screening, Weeks 9-12 and Weeks 21-24
Secondary outcome [7] 0 0
Change From Baseline in Frequency of Vomiting
Timepoint [7] 0 0
Screening, Weeks 9-12 and Weeks 21-24
Secondary outcome [8] 0 0
Change From Baseline in Percentage of Days With Vomiting
Timepoint [8] 0 0
Screening, Weeks 9-12 and Weeks 21-24
Secondary outcome [9] 0 0
Change From Baseline in Daily Degree of Difficulty With Drinking
Timepoint [9] 0 0
Screening, Weeks 9-12 and Weeks 21-24
Secondary outcome [10] 0 0
Change From Baseline in Pain With Drinking Severity Scores
Timepoint [10] 0 0
Screening, Weeks 9-12 and Weeks 21-24
Secondary outcome [11] 0 0
Change From Baseline in Percentage of Days on Which the Participant Drank
Timepoint [11] 0 0
Screening, Weeks 9-12 and Weeks 21-24
Secondary outcome [12] 0 0
Change From Baseline in Difficulty With Eating Solid Foods
Timepoint [12] 0 0
Screening, Weeks 9-12 and Weeks 21-24
Secondary outcome [13] 0 0
Change in Baseline in Pain With Eating Solid Foods Severity Scores
Timepoint [13] 0 0
Screening, Weeks 9-12 and Weeks 21-24
Secondary outcome [14] 0 0
Change From Baseline in the Percentage of Days Participants Ate Solid Foods
Timepoint [14] 0 0
Screening, Weeks 9-12 and Weeks 21-24
Secondary outcome [15] 0 0
Change From Baseline in Feeling of Something Stuck in Throat Bothersome Scores (for Par. 8-17 Years Only)
Timepoint [15] 0 0
Screening, Weeks 9-12 and Weeks 21-24
Secondary outcome [16] 0 0
Change From Baseline in Percentage of Days With Feeling of Something Stuck in Throat (for Par. 8-17 Years)
Timepoint [16] 0 0
Screening, Weeks 9-12 and Weeks 21-24
Secondary outcome [17] 0 0
Number of Participants With Maintenance of Response
Timepoint [17] 0 0
Week 12 and Week 24
Secondary outcome [18] 0 0
Mean Change From Baseline in Peak Esophageal Eosinophil Counts at Weeks 12 and 24
Timepoint [18] 0 0
Baseline, Weeks 12 and 24
Secondary outcome [19] 0 0
Change From Baseline in Mean Esophageal Eosinophil Counts at Weeks 12 and 24
Timepoint [19] 0 0
Baseline, Weeks 12 and 24
Secondary outcome [20] 0 0
Absolute Blood Eosinophils Count at the Indicated Time Points
Timepoint [20] 0 0
Screening, Day 1, Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24 and 34
Secondary outcome [21] 0 0
Plasma Concentration of Mepolizumab
Timepoint [21] 0 0
Day 1, Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24 and 34

Eligibility
Key inclusion criteria
* A subject will be eligible for inclusion in this study only if all of the following criteria apply. Inclusion criteria pertain to all subjects in both cohorts (treatment and observational) unless otherwise stated.
* The subject signs and dates a written assent form (age appropriate) and the parent/guardian signs and dates a written informed consent form prior to the initiation of any study-related activities, including discontinuation of any prohibited medications.
* Male or female subjects aged 2 to 17 years (from 2nd birthday up to and not including 18th birthday), who weigh <=84.9kg (males)/ <= 72.5 (females) and who have a BMI between 5 and 85% for age, who speak, read and write English as age appropriate and/or parent/guardian.

NOTE: If subject is within weight requirements but close to the upper or lower limits at screening and the investigator anticipates that during the study the subject's weight will change a become outside the weight requirements, the subject should be excluded from the study.

* To be eligible for entry in the treatment group of the study, a female subject is eligible to enter the study if she is: not pregnant or nursing; of non-childbearing potential. Non-childbearing potential is defined as a pre-menarcheal female who has not yet entered puberty as evidenced by lack of breast development (palpable glandular breast tissue); or a female who has documentation (medical report verification) of hysterectomy and/or bilateral oophorectomy; of childbearing potential. These females subjects must have a negative urine pregnancy test at the screening visit, and agree to consistent and correct use of one of the acceptable methods of birth control from at least the commencement of their last normal period prior to the first dose of study medication and to continue until the first normal period after treatment or after the Week 24 Follow-up visit, whichever is longest.
* The subject has a diagnosis of eosinophilic esophagitis and current evidence on biopsy of isolated eosinophilic esophagitis defined as:
* Peak esophageal eosinophil counts (highest count of eosinophils per HPF in at least one of all esophageal sites biopsied) of 20 or more eosinophils in a minimum of one HPF at 400X magnification on histology of esophageal biopsies from distal and mid-esophagus within two weeks of commencing study medication, as determined by the central histopathologist.
* Inadequate response to or intolerant of therapy for eosinophilic esophagitis
* The individual investigators will apply their clinical judgment to define whether a clinical response to therapy for eosinophilic esophagitis is inadequate. As guidance, inadequate response might consist of persistence under current or recent prior therapy, of symptoms of eosinophilic esophagitis such as eosinophilic esophagitis-related pain in stomach, chest or throat; regurgitation; vomiting; pain or difficulties associated with drinking fluids or nutritional supplements; or pain or difficulties associated with eating. An inadequate response might also consist of persistent eosinophilic infiltration of the esophagus, in the presence or in the absence of eosinophilic esophagitis-related symptoms.
* Similarly, the individual investigators will apply their clinical judgment to define whether a patient is intolerant to therapy. For guidance, intolerance to therapy for eosinophilic esophagitis may consist of undesirable side-effects of long-term therapy; or side-effects of long-term therapy that are difficult to manage; or marked non-compliance to therapy or rejection of therapy by the individual patient, or by the parent/guardian, which in the opinion of the investigator interferes with the patient's optimal disease management.
* The criteria used by the investigator to define inadequate response to or intolerance of therapy for eosinophilic esophagitis will be collected in the CRF.
Minimum age
2 Years
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* A subject will not be eligible for inclusion in this study if any of the following criteria apply. Exclusion criteria pertain to all subjects in both cohorts (treatment and observational) unless otherwise stated.
* Current evidence of eosinophilic gastrointestinal enteropathy (EGID), other than eosinophilic esophagitis.
* Evidence of gastroesophageal reflux disease, or other causes of esophagitis which in the investigator's opinion is the predominant cause of the subject's esophageal eosinophilia so that the investigator's opinion is allowed.
* Current presence, or history of (anytime in the past): hypereosinophilic syndromes, collagen vascular disease, vasculitis, allergic drug reaction as the cause of the peripheral eosinophilia, graft-versus host disease, chronic idiopathic inflammatory bowel disorders (ulcerative colitis, Crohn's disease, chronic granulomatous disease).
* Current evidence, or history of celiac disease.
* Current evidence of active H. pylori infection.
* Abnormal 12-lead ECG at Screening which is clinically significant in the opinion of the investigator. Note that this exclusion criterion does not apply for subjects who are considered for enrollment in the observational cohort.
* Use or administration of any of the prohibited medications from Screening and throughout completion of Week 34 follow-up. Note that this exclusion criterion does not apply for subjects who are considered for enrollment in the observational cohort.
* Failure to remain on a stable dose of one (or more) permitted medication(s) for at least 1 month prior to the Screening visit and throughout completion of Week 24 follow-up assessments. Note that this exclusion criterion does not apply for subjects who are considered for enrollment in the observational cohort.
* Failure to remain on stable elemental diet or dietary manipulations for at least 3 months prior to the Screening Visit and throughout completion of Week 34 follow-up assessments. Note that this exclusion criterion does not apply for subjects who are considered for enrollment in the observational cohort.
* Known history of allergic reaction to previous antibody therapy.
* Any previous treatment with anti-hIL-5, anti-IgE monoclonal antibody or other biological agents.
* Use of an investigational drug within 30 days of entering the study. Note that this exclusion criterion does not apply for subjects who are considered for enrollment in the observational cohort.
* Exhibits evidence of renal disease or serum creatinine > 1.5 times upper limit of normal range (ULN). Note that this exclusion criterion does not apply for subjects who are considered for enrollment in the observational cohort.
* Exhibits evidence of hepatic disease, impairment or abnormal liver function test i.e. AST, ALT >1.5 times ULN, bilirubin >1.5 times ULN. Note that this exclusion criterion does not apply for subjects who are considered for enrollment in the observational cohort.
* Known evidence of the following infections/infestations: HIV, Hepatitis B or C, Bacterial infection, Parasitic infestation.
* History or suspicion of current drug abuse and alcohol abuse within the last 6 months.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
11/09/2006
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
25/11/2008
Sample size
Target
Accrual to date
Final
84
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
GSK Investigational Site - Brisbane
Recruitment postcode(s) [1] 0 0
4029 - Brisbane
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Indiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Michigan
Country [9] 0 0
United States of America
State/province [9] 0 0
Minnesota
Country [10] 0 0
United States of America
State/province [10] 0 0
Missouri
Country [11] 0 0
United States of America
State/province [11] 0 0
New York
Country [12] 0 0
United States of America
State/province [12] 0 0
Ohio
Country [13] 0 0
United States of America
State/province [13] 0 0
South Dakota
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
United States of America
State/province [15] 0 0
Virginia
Country [16] 0 0
United States of America
State/province [16] 0 0
Wisconsin
Country [17] 0 0
Canada
State/province [17] 0 0
Ontario
Country [18] 0 0
Canada
State/province [18] 0 0
Quebec
Country [19] 0 0
United Kingdom
State/province [19] 0 0
Liverpool
Country [20] 0 0
United Kingdom
State/province [20] 0 0
London
Country [21] 0 0
United Kingdom
State/province [21] 0 0
Sheffield
Country [22] 0 0
United Kingdom
State/province [22] 0 0
Watford

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT00358449