This study has been transitioned to CTIS with ID 2023-504277-20-00 check the CTIS register for the current data. The aim of this global Phase III study is to investigate the use of tezepelumab as a treatment for patients with EoE. This study will…
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- To evaluate the effect of tezepelumab on the histologic response in adult and
adolescent participants with symptomatic and histologically active EoE
- To evaluate the effect of tezepelumab on symptom improvement in adult and
adolescent participants with symptomatic and histologically active EoE
Secondary outcome
Key Secondary
- To evaluate the effect of tezepelumab on the centrally-read EoE EREFS
- To evaluate the effect of tezepelumab on the centrally-read EoE-HSS
- To evaluate the long-term effect of tezepelumab on the histologic response
- To evaluate the long-term effect of tezepelumab on symptom improvement
- To evaluate the long-term effect of tezepelumab on the centrally-read EoE
EREFS
- To evaluate the effect of tezepelumab on achievement of clinico-histological
remission
see table 7 for all Objectives and Endpoints
Background summary
Eosinophilic esophagitis (EoE) is a rare, chronic inflammatory disorder
triggered by an immune response to foods and aeroantigens and characterizedby a
combination of esophageal dysfunction and eosinophilic infiltration of the
esophagus. Thymic stromal lymphopoietin (TSLP) is produced in response to
pro-inflammatory stimuli and drives allergic inflammatoryresponses, primarily
through its activity on type 2 innate lymphoid cells, dendritic and mast cells,
which release an abundance of mediators that attract and activate eosinophils
as well as molecules that directly promote tissue remodeling including
fibrosis. TSLP-driven eosinophilic inflammation is a central finding in EoE.
Tezepelumab is a human immunoglobulin G (IgG)2* monoclonal antibody (mAb) that
selectively blocks TSLP from interacting with its heterodimeric receptor. By
blocking the interaction of TSLP with its heterodimeric receptor and
interfering with multiple downstream inflammatory pathways, tezepelumab has the
potential to reduce the initiation and persistence of esophageal eosinophilia,
inflammation, and fibrosis, which are important factors in the pathogenesis of
EoE.
Study objective
This study has been transitioned to CTIS with ID 2023-504277-20-00 check the CTIS register for the current data.
The aim of this global Phase III study is to investigate the use of tezepelumab
as a treatment for patients with EoE. This study will evaluate the efficacy and
safety of tezepelumab 210 mg every 4 weeks (Q4W) and tezepelumab 420mg Q4W
administered subcutaneously (SC) using an accessorized pre-filled syringe
(APFS) versus placebo in adult and adolescent participants with EoE. In 2021,
tezepelumab was granted Orphan Drug Designation in the US by the FDA for the
treatment of EoE
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Study design
Overall Design
This is a Phase III, randomized, double-blind, parallel-group,
placebo-controlled, multicenter study to evaluate the efficacy and safety of
repeat dosing of tezepelumab administered SC using an APFS versus placebo in
adult and adolescent participants with EoE.
This study will randomize approximately 360 participants1:1:1 to receive either
210 mg tezepelumab, 420 mg tezepelumab, or placebo, administered SC Q4W.
Randomization will be stratified by region (Asia vs Rest of World), age
category (adults vs adolescents), and baseline swallowed topical
corticosteroids (STC) use (yes vs no).
The study consists of a screening/run-in period of 2 to 8 weeks and a 52-week
randomized double-blind placebo-controlled treatment period. After completion
of the treatment period, participants will be eligible to participate in an
active treatment extension period (lasting for a minimum of 24 weeks), followed
by a 12-week off-treatment safety follow-up period. Participants who will not
participate in the extension period will participate in a 12-week off-treatment
safety follow-up period following completion of the 52-week treatment period.
Two interim analyses (IAs) for futility are planned for this study. The first
IA will be performed after approximately 15% of study participants
(approximately 54 adult participants) have completed Week 24. The second IA
will be performed after approximately 40% of study participants (approximately
144 participants) have completed Week 24. The study team will remain blinded to
the interim data. A Data Monitoring Committee (DMC) will review the unblinded
efficacy and safety data and make recommendation to stop the 210 mg Q4W dose or
both doses for futility. If the study is not stopped at the first IA for
futility or safety, enrollment of adolescent participants will start following
the recommendation of the DMC. Details of the 2 planned IAs are provided in
Section 9.4. Further details of the role of the DMC are provided in Section9.5.
Intervention
Following informed consent or assent (if applicable), all participants will
enter a screening/run-in period of 2 to 8 weeks. Following this, participants
confirmed to be eligible will be randomized 1:1:1 to receive either 210 mg Q4W
tezepelumab, 420 mg Q4W tezepelumab, or placebo administered by SC injections
for 52 weeks. There will then be a 12-week off-treatment safety follow-up
period for participants who do not continue in the active treatment extension
period. For these participants, the maximum duration of the study will be 72
weeks in total.
Study burden and risks
During the double-blind treatment period, the subject is asked to visit the
hospital at least 15 times. Each visit will last 1-3 hours and if an endoscopy
is made 6 hours.
For the extended treatment period, the subject is asked to visit the hospital
at least 12 times. Each visit will last 1-4 hours.
The subject will receive study drug 12 times during 52 weeks. If the subject
participates in the extension of the study, the subject will receive the study
drug 18 times during 78 weeks. The study drug may cause allergic reactions. A
study physician will be present at the time of study drug administration and
will observe the subject for 1-2 hours after study drug administration. In
addition, the test subject may experience side effects from the study drug.
Blood samples will be taken during the study. The total blood volume that will
be collected during the first year is 266 ml.
The subject will have a physical examination during each visit.
The subject will undergo endoscopy including biopsies at least 4 times during
the study. Endoscopies carry risks and inconveniences, but the number of
endoscopies is equal to the number of endoscopies in standard practice.
An EKG is taken four times.
Women of childbearing potential will be required to provide a urine sample to
perform a pregnancy test during the screening visit and each time before study
drug administration (17 times).
The subject is asked to complete questionnaires during each hospital visit.
The subject will complete daily, weekly and monthly questionnaires in an
electronic diary. This will take about 5 minutes per day.
Prinses Beatrixlaan 582
Den Haag 2595BM
NL
Prinses Beatrixlaan 582
Den Haag 2595BM
NL
Listed location countries
Age
Inclusion criteria
1. Participant must be 12 to 80 years of age inclusive, at the time of signing
the informed
consent/assent.The protocol indicated that subjects between 12 and 80 years old
can participate. In the Netherlands it is decided that only subjects between
the 18 and 80 can participate.
2. Weight >= 40 kg at Visit 1.
3. Previously established diagnosis of EoE by EGD and esophageal biopsy.
4. Participants who have symptomatic EoE as defined by a history of on average
at least 2 episodes of dysphagia (any severity of food going down slowly or
being stuck in the throat) per week in the 4 weeks prior to Visit 1.
5. Must have been on stabilized diet for at least 8 weeks prior to Visit 1 and
be willing to remain on stabilized diet during the course of the study (stable
diet is defined as no initiation of single or multiple elimination diets or
reintroduction of previously eliminated food groups).
6 . May be on any background medication for EoE, for example PPI and/or STC,
during the course of the study, as long as background medications have been
stable for at least 8 weeks prior to the screening/run-in period (Visit 1) and
there is agreement not to change background medication or dosage unless
medically indicated, during the screening/run-in and treatment period.
7. Participants should have previously documented standard of care treatment,
which could include PPI and/or STC and/or diet.
8. Participants currently on leukotriene inhibitors and/or steroid treatments
for asthma or allergies that are inhaled or administered intranasally, must
report a stable dose for at least 4 weeks prior to the screening/run-in period
(Visit 1).
9. Participants with either of the following:
(a) If a medication for EoE (for example PPI and/or STC) is discontinued prior
to the screening/run-in, there should be a washout period of at least 8 weeks
prior to Visit 1.
(b) Discontinuation of any marketed biologic (monoclonal or polyclonal
antibody) should have a washout period of 4 months or 5 half-lives prior to
Visit 1, whichever is longer.
Exclusion criteria
1. Other gastrointestinal disorders such as active Helicobacter pylori
infection, history of achalasia, esophageal varices, Crohn's disease,
ulcerative colitis, inflammatory bowel disease, celiac disease, EGE, EG,
eosinophilic enteritis,colitis, diverticulitis, irritable bowel syndrome, or
other clinically significant gastrointestinal conditions as per investigator
discretion.
2. Eosinophilic granulomatosis with polyangiitis vasculitis.
3. Esophageal stricture that prevents the easy passage of a standard endoscope
or any critical esophageal stricture that requires dilation at screening.
4. Use of a feeding tube, or having a pattern of not eating solid food >= 3 days
of the week.
Solid food is defined as food that requires chewing before swallowing.
5. Hypereosinophilic syndrome
6. Esophageal dilation performed within 8 weeks prior to screening.
see section 5.2 of the protocol for a complete overview of all exclusion
criteria.
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 |
|---|---|
| Other | IND 156401 |
| EU-CTR | CTIS2023-504277-20-00 |
| EudraCT | EUCTR2022-001294-31-NL |
| CCMO | NL82040.018.22 |