The objectives of this open-label extension safety monitoring (OLE-SM) study are as follows:Part 1 (Open-Label Extension; OLE)• To assess the long-term safety and efficacy of etrolizumab in patients eligible for Part 1 (OLE)Part 2 (Safety Monitoring…
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The efficacy outcome measure for this study is as follows:
• To describe the long-term efficacy of etrolizumab (105 mg SC every 4 weeks)
by pMCS for patients with UC in Part 1 (OLE)
• To evaluate remission by MCS at Week 108 in Part 1 (OLE)
• To evaluate endoscopic remission by MCS at Week 108 in Part 1 (OLE)
• Incidence of adverse events
Secondary outcome
The safety outcome measures for this study are as follows:
Part 1 (OLE)
• Incidence and severity of adverse events
• Incidence of serious adverse events
• Incidence and severity of infection-related adverse events
• Incidence of serious infection-related adverse events
• Incidence and severity of injection-site reactions
• Incidence of adverse events leading to etrolizumab discontinuation
• Incidence of laboratory abnormalities
• Incidence of malignancies
• Incidence of anti-therapeutic antibodies (ATAs) to etrolizumab
• Incidence and severity of hypersensitivity reaction events
Part 2 (SM)
• Incidence of suspected or confirmed PML events
Background summary
UC is characterized by mucosal ulceration, rectal bleeding, diarrhea, and
abdominal pain and may be complicated by severe bloody diarrhea and toxic
megacolon, requiring major and sometimes urgent surgery.
The overall incidence of UC ranges from 6.3 to 24.3 cases per 100,000 persons
per year, and prevalence ranges from 4.9 to 505.0 cases per 100,000 persons,
with the highest estimates in European and Northern American populations.
The goals of treatment are to induce and maintain remission, decrease
corticosteroid use (as measured by steroid-free remission), induce mucosal
healing, reduce hospitalization and surgery, improve quality of life (QOL), and
avoid disability.
The current treatments are associated with significant adverse events,
resulting in low rates of sustained remission, or are highly invasive. Targeted
therapy with an improved safety profile and ability to sustain remission and
prevent long-term complications would provide a valuable therapeutic option for
these patients. Consequently, the potential benefits of etrolizumab in this
population warrant further investigation.
This study investigates the long-term safety of patients with UC who were
initially treated in Phase III UC studies and includes long-term monitoring for
progressive multifocal leukoencephalopathy (PML).
More information can be found in the protocol.
Study objective
The objectives of this open-label extension safety monitoring (OLE-SM) study
are as follows:
Part 1 (Open-Label Extension; OLE)
• To assess the long-term safety and efficacy of etrolizumab in patients
eligible for Part 1 (OLE)
Part 2 (Safety Monitoring; SM)
•Progressive multifocal leukoencephalopathy (PML) safety monitoring
Safety Objectives
The other safety objectives for this study are as follows:
Part 1 (OLE)
• To evaluate the incidence and severity of infection-related adverse events
• To evaluate the incidence of malignancies
• To evaluate the incidence and severity of hypersensitivity reactions
• To evaluate the incidence and the clinical significance of anti-therapeutic
antibodies (ATAs)
Study design
This OLE-SM study is composed of two parts:
• Part 1 is the OLE for eligible patients, during which active etrolizumab, 105
mg subcutaneous (SC), will be administered every 4 weeks followed by a 12-week
safety follow-up.
• Part 2 is the 92-week PML safety monitoring for all patients, during which no
etrolizumab will be administered.
Patients who are enrolled in Part 1 (OLE) should participate in Part 1 (OLE)
and Part 2 (SM). There may be patients who are ineligible for or choose not to
participate in Part 1 (OLE) who will directly enroll in Part 2 (SM) only.
Intervention
Etrolizumab prefilled syringe (PFS): containing SC formulation, 105 mg given as
0.7 mL of a 150-mg/mL solution will be administered by SC injection every 4
weeks.
Study burden and risks
In this study etrolizumab is being assessed for induction and long-term
maintenance therapy. Therefore, this study is being conducted to treat patients
with etrolizumab in an open-label fashion in order to assess the long-term
safety and efficacy.
The benifit of this design is that no patient will be exposed to risk of not
receiving any treatment.
There may be side effects, risks, discomforts associated with etrolizumab, the
study procedures or reproductive risks for patients participating in this
trial. These can vary from person to person and can go from mild to very
serious. Everyone taking part in the study will be watched carefully for any
side effect.
Patients are asked to visit the clinic as indicated by the protocol and do the
following procedures (amongst others):
- Pregnancy tests (if applicable)
- Physical exams
- PML neuro exams
- ECGs
- HBV test
- Completion of e-diary
- Blooddraws
- Examination of gastrointestinal tract
- Subcutaneous IP injections
For more details regarding the risks, side effects and study procedures please
refer to the informed consent form.
Grenzacherstrasse 124 Grenzacherstrasse 124
Basel 4070
CH
Grenzacherstrasse 124 Grenzacherstrasse 124
Basel 4070
CH
Listed location countries
Age
Inclusion criteria
Part 1 (Open-label Extension; OLE), - Patients previously enrolled in Phase III
controlled studies who meet the eligibility criteria for open-label etrolizumab
for those studies as described in the protocol, Part 2 (Safety Monitoring; SM),
- Patients who participated in one of the etrolizumab Phase III studies and are
not eligible or chose not to enter Part 1 (OLE)
- Patients who transfer from Part 1 (OLE)
- Completion of the 12-week safety follow-up prior to entering., A complete
list of inclusion criteria can be found in the protocol
Exclusion criteria
Part 1 (Open-label Extension; OLE), - Any new, significant, uncontrolled
condition
- Receipt of the following since commencement of the Phase II OLE or
Phase III controlled studies: Use of anti-adhesion molecules, Part 2 (Safety
Monitoring; SM), - No exclusion criteria, A complete list of exclusion criteria
can be found in the protocol
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 | EUCTR2013-004435-72-NL |
| ClinicalTrials.gov | NCT02118584 |
| CCMO | NL48053.018.14 |