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…
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The efficacy outcome measures for this study are as follows:
• CDAI remission assessed at 12-week intervals during Part 1 (OLE)
• PRO2 remission assessed at 12-week intervals during Part 1 (OLE)
The safety outcome measures for Part 1 of this study are as follows:
• Incidence and severity of adverse events
• Incidence of serious adverse events
• Incidence, rate per subject-year, 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 and rate per subject-year of malignancies
• Incidence of ATAs to etrolizumab
• Incidence and severity of hypersensitivity reactions
The safety outcome measure for Part 2 of this study is as follows:
• Incidence of suspected or confirmed PML events
Secondary outcome
NA
Background summary
So far, there is no cure for CD. The treatment goals for CD are to induce and
maintain symptom improvement, induce mucosal healing, avoid surgery, and
improve quality of life. Etrolizumab, a subcutaneously administered mAb, is a
novel anti-integrin that, like vedolizumab, targets the α4β7 receptors that
regulates trafficking of T-cell subsets in the intestinal mucosa, but unlike
vedolizumab, etrolizumab also targets the αEβ7 receptors that regulate
retention of T-cell subsets in the intestinal mucosa. Thus, etrolizumab offers
the potential of an additive therapeutic effect in CD via a dual mechanism of
action (MOA) without generalized immunosuppression.
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 in
patients who have stopped study treatment
Safety Objectives
The other safety objectives for this study are as follows:
Part 1 (OLE)
• To evaluate the incidence, rate per subject-year, and severity of
infection-related adverse events
• To evaluate the incidence and rate per subject-year 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 etrolizumab, 105 mg
subcutaneous (SC), will be administered every 4 weeks (Q4W) followed by a
12-week safety follow-up post-treatment.
• Part 2 is the 92-week PML SM for all patients, during which no etrolizumab
will be administered.
Patients who are enrolled in Part 1 (OLE) should participate in Part 2 (SM).
There may be patients from Study GA29144 who are ineligible for or choose not
to participate in Part 1 (OLE) who will be asked to directly enroll in Part 2
(SM).
Intervention
Every 4 weeks an SC-injections with etrolizumab
Study burden and risks
The current therapeutic options available for CD include corticosteroids,
immunosuppressants, and biological agents. These treatments reduce symptoms and
improve quality of life; however, patients often stop responding to treatments
and the goals of maintaining clinical remission and healing mucosal
inflammation are not achieved. Moreover, these therapies are associated with
adverse effects including diabetes (reported with corticosteroid use;
Peyrin-Boulet et al. 2010), systemic toxicities such as leucopenia and
thrombocytopenia (reported with immunosuppressant use; Prefontaine et al.
2009), and an increased risk for lymphoma and serious and opportunistic
infections (reported with immunosuppressant and anti-TNF use when given as
monotherapy or in combination; Siegal and Melmed 2009).
The anti-integrins are another class of biologics approved for the treatment of
CD. The reported efficacy of the recently licensed anti-integrin vedolizumab,
an intravenously administered anti-α4β7 mAb, in CD demonstrates a role for α4β7
in the pathobiology of this disease (Sandborn et al. 2013). In addition to
demonstrating efficacy compared with placebo, vedolizumab had an acceptable
safety profile in two Phase III trials for CD (Sandborn et al. 2013; Sands et
al. 2014). Although long-term safety data for vedolizumab is still being
collected and is not yet published, to date no cases of PML have been reported.
Grenzacherstrasse 124 -
Basel 4070
CH
Grenzacherstrasse 124 -
Basel 4070
CH
Listed location countries
Age
Inclusion criteria
Patients must meet the following criteria for study entry:
Part 1 (OLE)
• Patients who were previously enrolled in Study GA29144 and experienced any of
the following:
Disease worsening in the Induction Phase of Study GA29144, defined as both CDAI
and PRO2 scores at Week 10 or later in the Induction Phase being greater than
the patient*s baseline (Week 0) score
Did not achieve CDAI-70 response at Week 14 in Study GA29144
A clinical relapse in Study GA29144, defined as >= 100-point increase in CDAI
score from the Week 14 CDAI score on two consecutive visits (which may include
unscheduled visits) and a CDAI score >= 220 points
Completed the Maintenance Phase including the Week 74 clinic visit in Study
GA29144
• Ability and willingness to provide written informed consent and comply with
the requirements of the OLE-SM protocol.
• For women who are not postmenopausal (at least 12 months of
non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries
and/or uterus): agreement to remain abstinent or to use a highly effective
method of contraception during the treatment period and for at least 24 weeks
after the last dose of study drug.
Abstinence is acceptable only if it is in line with the preferred and usual
lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation,
symptothermal, or postovulation methods) and withdrawal are not acceptable
methods of contraception.
• For men: agreement to remain abstinent or to use a condom during the
treatment period and for at least 24 weeks after the last dose of study drug
Abstinence is acceptable only if it is in line with the preferred and usual
lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation,
symptothermal, or postovulation methods) and withdrawal are not acceptable
methods of contraception.
PART 2 (SM)
• Patients who participated in Study GA29144 and are not eligible or chose not
to enroll in Part 1 (OLE)
• Patients who participated in Part 1 (OLE) of this protocol
• Ability and willingness to provide written informed consent and comply with
the requirements of Part 2 (SM) of the OLE-SM protocol
All patients must have completed the 12-week safety follow-up prior to entering
Part 2 (SM).
Exclusion criteria
Patients who meet any of the following criteria will be excluded from study
entry:
Part 1 (OLE)
• Patients who leave Study GA29144 before Week 10
• Patients who do not perform the Week 14 visit in Study GA29144 , except for
those escaping between Weeks 10 and 14 for disease worsening
• Patients who discontinue study drug in the Induction Phase of Study GA29144,
except for those escaping between Weeks 10 and 14 due to disease worsening
• Patients who received rescue therapy in the absence of disease worsening
during the Induction Phase of Study GA29144
• Patients who received rescue therapy in the absence of clinical relapse
during the Maintenance Phase of Study GA29144 will not be eligible for Part 1
(OLE) until completing the Week 74 visit in Study GA29144
• Patients who received medications that are prohibited in conjunction with
etrolizumab (see protocol)
• Patients participating at U.S investigational sites who require continued use
of immunosuppressant therapy beyond a total of 14 weeks of co-administration
with study drug in Study GA29144 are ineligible for Part 1 (OLE).
• Inability to comply with the study protocol, in the opinion of the
investigator
• Pregnancy or lactation
• Patients who developed an anaphylactic/anaphylactoid or severe allergic
reaction to study medication during Study GA29144
• Patients who have an untreated or unresolved serious infection event
• Patients who experienced a de novo or reactivated serious viral infection
such as hepatitis B virus (HBV), hepatitis C virus (HCV), or HIV during Study
GA29144
• Patients who developed life-threatening infections during Study GA29144
• Patients who developed a malignancy (with the exception of non-serious local
and resectable basal or squamous cell carcinoma of the skin) or who develop
adenocarcinoma in situ (AIS), high-grade squamous intraepithelial lesions
(HSIL), or cervical intraepithelial neoplasia (CIN) of Grade > 1 on cervical
Pap smear or who develop colonic dysplasia during Study GA29144
• Receipt of the following since commencement of Study GA29144:
Any investigational treatment, including investigational vaccines
Use of T or B cell depleting agents (e.g., rituximab, alemtuzumab or
visilizumab)
Use of cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil (MMF)
Use of natalizumab, vedolizumab, or efalizumab
Use of TNF antagonists
Immunization with a live/attenuated vaccine
• In the opinion of the investigator, any new (since enrolling in Study
GA29144), significant, uncontrolled comorbidity, such as neurological, cardiac
(e.g., moderate to severe heart failure New York Heart Association [NYHA] Class
III/IV), pulmonary, renal, hepatic, endocrine, or gastrointestinal (GI)
disorders (excluding CD)
• Any patient who developed PML in Study GA29144
• Any patient with neurological symptoms where suspected PML has not been ruled
out
Part 2 (SM)
• No 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 |
|---|---|
| EudraCT | EUCTR2014-003855-76-NL |
| CCMO | NL52292.018.15 |