The Budesonide oral suspension is a new drug formulation especially developed for the treatment of eosinophile esophagitis in children and adolescents. The purpose of this clinical study is to investigate whether Budesonide oral suspension is…
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
• Rate of patients with pathological remission and clinical response at DB week
12 (LOCF) defined as fulfilling both criteria:
- Histological remission, i.e., peak of <16 eos/mm2 hpf at DB week 12 (LOCF),
AND
- Clinical response defined as:
Stratum I: Age 2 to 11 years at DB V1:
>=30% drop in the total score of PEESS® Version 2.0 - parent report for children
and teens (ages 2-18) from baseline to DB week 12 (LOCF),
- Stratum II: Age 12 to <18 years at DB V1:
>=30% drop in the total score of PEESS® Version 2.0 - children and teens report
(ages 8-18) from baseline to DB week 12 (LOCF).
Patients who experience either a food impaction which needs endoscopic
intervention, or who need an endoscopic dilation at any time during the
DB-treatment phase, or who were prematurely withdrawn due to lack of efficacy
after at least 8 weeks of DB treatment and who showed no change or a
deterioration in the Global Assessment Score (ParGA/PatGA) compared to baseline
at their last visit in the DB-treatment phase (DB V4 EOT/withdrawal DB), will
be assessed as treatment failures, and thus will not fulfill by definition the
*pathological remission and clinical response* criterion. These patients still
can be treated with verum budesonide in the open label induction phase.
Secondary outcome
A priori ordered key secondary efficacy endpoints (DB-phase):
1. Rate of patients with histological remission, defined as a peak of
<16 eos/mm2 hpf at DB week 12 (LOCF),
2. Change in the peak eos/mm2 hpf from screening to DB week 12 (LOCF),
3. Rate of patients with clinico-pathological remission defined as:
• Histological remission, i.e., peak of <16 eos/mm2 hpf at DB
week 12 (LOCF), and
o Clinical remission (i.e., no or only minimal problems) defined as clinical
response (>=30% drop in the total score of PEESS® Version
2.0 from baseline to DB week 12 [LOCF]) AND
Stratum I: Age 2 to 11 years at DB V1:
PEESS® Version 2.0 - parent report for children and teens (ages 2- 18)
• <=4 points in each of the subdomains GERD/nausea- vomiting/pain, and
• <=7 points in the subdomain dysphagia,
or
• <=5 points in the total score and >=2 subdomains with a drop of at least 50%
compared to baseline
at DB week 12 (LOCF),
Stratum II: Age 12 to <18 years at DB V1:
PEESS® Version 2.0 - children and teens report (ages 8-18)
• <=4 points in each of the subdomains GERD/nausea- vomiting/pain, and
• <=7 points in the subdomain dysphagia,
or
• <=5 points in the total score and >=2 subdomains with a drop of at least 50%
compared to baseline
at DB week 12 (LOCF),
4. Rate of patients with clinical remission (i.e., no or only minimal problems)
defined as above (clinical remission component of the endpoint
clinico-pathological remission) at DB week 12 (LOCF),
5. Rate of patients with clinical response at DB week 12 (LOCF), defined as
Stratum I: Age 2 to 11 years at DB V1:
>=30% drop in the total score of PEESS® Version 2.0 - parent report for children
and teens (ages 2-18) from baseline to DB week 12 (LOCF), Stratum II: Age 12 to
<18 years at DB V1:
>=30% drop in the total score of PEESS® Version 2.0 - children and teens report
(ages 8-18) from baseline to DB week 12 (LOCF)
6. In the subgroup of patients with >=4 points in NRS for dysphagia on the day
of the baseline visit (only patients of Stratum II: Age 12 to <18 years at DB
V1), the rate of patients with resolution of dysphagia symptom (i.e., no or
only minimal problems). Resolution of dysphagia symptom is defined as
• a severity of <=2 points on 0 to 10-point (0-10) NRS on each day in the week
prior to DB week 12 (LOCF).
Background summary
Recent studies suggest that swallowing budesonide is effective in the treatment
of EoE, and can bring the disease in remission, and possbly maintians this for
a longer period of time, while it might not be associated with the toxicities
of long term use of systemic corticosteroids.
Study objective
The Budesonide oral suspension is a new drug formulation especially developed
for the treatment of eosinophile esophagitis in children and adolescents. The
purpose of this clinical study is to investigate whether Budesonide oral
suspension is effective for induction of remission in children and adolescents
with active EoE. Also see protocol paragraph 2.
Study design
This is a double-blind, randomized, multicenter, placebo-controlled,
comparative, Phase II/III clinical trial in children and adolescents with EoE,
>=2 to <18 years of age.
Intervention
The trial will be conducted with three treatment groups in the form of a
parallel group comparison and will primarily serve to compare a 12-week oral
treatment with different daily doses of budesonide oral suspension vs. placebo
for the treatment of active EoE in a double-blind manner. The up to 4-week
screening period will be followed by a 12-week double-blind (DB) treatment
period, an optional 12-week open-label induction (OLI) treatment for eligible
patients, an optional 24-week open-label extension (OLE) treatment with
budesonide oral suspension for eligible patients, a 3-week tapering phase, and
a 4-week follow-up period after the patient*s last end of treatment visit.
Study treatments (test drug and/or placebo) will be administered orally twice
daily during the respective treatment phase, once in the morning after
breakfast and once in the evening after the meal (except for the OLE phase
where once or twice daily dosing is given based on the decision of the
investigator, and except for the tapering phase with only one dose per day).
Study burden and risks
physical examiniation 4 times, inclusive review of pubertal stage and
measurement of head circumference (in chlidren up to 5 years)
endoscopy of the esophagus with biopsies 2-3 times; under deep sedation (from
10 years onwards) or narcosis (up to and including 9 years)
questionnaires related to complaints and disease: 4 questionnaires, per
questionnaire a variable frequuency
completion of a diary., daily in screening, OLI and DB phase
blood examination 6-12 times
urine examiniation 11 times
The adverse events are characteristic for steroid medication, and can occur
depending on the dosage, treatment period, whether the subject is or has been
taking other corticosteroid preparations, and the individual sensitivity.
Leinenweberstrasse 5
Freiburg 79108
DE
Leinenweberstrasse 5
Freiburg 79108
DE
Listed location countries
Age
Inclusion criteria
Inclusion criteria for DB-treatment phase:
- Signed informed consent
- Male or female patients, >=2 to <18 years of age
- Confirmed clinico-pathological diagnosis of EoE according to established
diagnostic criteria
- Clinically and histologically active EoE
- Negative pregnancy test in female patients of childbearing potential
Exclusion criteria
Exclusion criteria for DB treatment phase:
- Erosive gastroesophageal reflux disease (GERD)
- Achalasia, scleroderma esophagus, or systemic sclerosis
- Other clinically evident causes than EoE for esophageal eosinophilia
- Any concomitant esophageal disease and relevant gastro-intestinal disease
(celiac disease, inflammatory bowel disease, oropharyngeal or esophageal
bacterial, viral, or untreated or inadequately treated fungal infection
[candida esophagitis])
- Any known relevant infectious diseases (e.g., AIDS defining disease, active
tuberculosis, hepatitis B, or hepatitis C)
- Diabetes mellitus
- If careful medical monitoring is not ensured: cardiovascular disease,
hypertension, osteoporosis, active peptic ulcer disease, glaucoma, cataract, or
infection
- History of cancer in the last five years
- History of esophageal surgery at any time or of esophageal dilation
procedures within the last 4 weeks prior to screening endoscopy, or need for an
immediate endoscopic intervention due to a stricture
- Upper gastrointestinal bleeding within 8 weeks prior to screening endoscopy
- Existing or intended pregnancy or breast-feeding
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-003737-29-NL |
| CCMO | NL68447.078.19 |