The primary objective of this study is:- To observe the long-term safety of filgotinib in subjects who have completed or met protocol specified efficacy discontinuation criteria in a prior filgotinib treatment study for CDThe secondary objective of…
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is safety. Safety will be evaluated through AEs, clinical
laboratory tests, and vital signs. Safety endpoints will be analyzed by the
number and percent of subjects with events or abnormalities for categorical
values or standard descriptive statistics (n, mean, standard deviation [SD],
median, 1st quartile [Q1], 3rd quartile [Q3], minimum, maximum) for continuous
data.
Secondary outcome
The secondary efficacy endpoints of change from baseline in PRO2 and CDAI
scores, and exploratory endpoints of change in HRQoL
scores will be summarized using standard descriptive statistics (n, mean, SD,
median, Q1, Q3, minimum, maximum).
Background summary
A significant change in CD management and therapeutic strategy has occurred
over the last decade. Recent therapeutic goals extend beyond symptomatic
control and include long-term mucosal and endoscopic remission. The ultimate
aim is to change the natural course of the
disease by slowing down or halting its progression, thus avoiding surgery or
hospitalization. This is believed to be achieved by utilizing earlier,
aggressive, and goal-directed therapy. Risk assessment and prediction by means
of complex clinical, biochemical, and endoscopic markers
has become the key to patient management, therapy optimization, and prediction
of the outcome and side effects of medical therapy. Many new treatments focus
on inhibiting, suppressing, or altering T-cell differentiation and homing.
Three monoclonal antibodies which inhibit tumor
necrosis factor-alpha (TNFα), are currently marketed for the treatment of CD:
infliximab (Remicade®), adalimumab (Humira® [approved in US and European Union
{EU}]) and certolizumab pegol (Cimzia® [approved in US]). More recently,
vedolizumab (Entivyo® [approved in US and EU]), a monoclonal antibody against
α4β7 integrin was approved by US Food and Drug Administration (FDA) and
European Medicines Agency (EMA). Other approaches include the administration of
cytokines to stimulate innate immunity and the use of prebiotics to alter the
gut flora. Blocking the interleukin (IL)-6 signaling pathway is also considered
a possible therapeutic strategy for CD: tocilizumab (RoActemra®), an anti-IL-6R
monoclonal antibody (mAb), showed promising results in an early pilot study
{Ito et al 2004} and a Phase 2 study is currently ongoing with the anti-IL-6
mAb PF-04236921. In addition, an oral antisense oligonucleotide (GED-0301) is
being evaluated for the treatment of CD showed
encouraging results in a Phase 2 study. Other new treatments being tested in
clinical trials includes janus kinase (JAK) inhibitors (eg, upadacitinib,
tofacitinib), IL-12/23 antagonist (ustekinumab [Stelara]), and a matrix
metallopeptidase-9 (MMP-9) inhibitor (GS-5745).
Leukocytapheresis therapy may be used in Japan {Fukunaga et al 2012}. Despite
currently available therapies, long-term or durable remission rates are still
low at approximately 20%. Furthermore, the risk of infection, and in rare cases
malignancy, limits the long-term use or use in vulnerable populations (eg,
children and those with comorbid disorders). Therefore, a need still exists for
safer and durable efficacious therapies for moderately to severely active CD.
Study objective
The primary objective of this study is:
- To observe the long-term safety of filgotinib in subjects who have completed
or met protocol specified efficacy discontinuation criteria in a prior
filgotinib treatment study for CD
The secondary objective of this study is:
- To evaluate the effect of filgotinib on Patient Reported Outcomes (PRO2) and
Crohn*s Disease Activity Index (CDAI) scores
Study design
This is a long-term extension study. Some subjects will receive open-label drug
and some will receive blinded dosing until subject*s treatment in the
corresponding parent study is unblinded. In general, subjects who fully
complete a parent study blinded will continue blinded dosing at thsame regimen
in the present study on 200 mg filgotinib, 100 mg filgotinib, or placebo. After
the corresponding parent study (GS-US-419-4015, GS-US-419-4016, or
GS-US-419-3895, or other Gilead/ Galapagos-sponsored filgotinib treatment
study) is unblinded, subjects enrolled in the present study may be unblinded.
Subjects who enroll from a parent study and receive blinded treatment in the
DIVERSITY LTE study will have their DIVERSITY
LTE treatment assignment unblinded when the parent study is unblinded.
Subjects will continue on the same dose of open-label filgotinib as they had
been receiving in blinded treatment. Subjects on placebo treatment will
discontinue study drug and study participation. Subjects who exit a parent
study due to disease worsening or failure to meet response or remission
criteria will receive open-label 200 mg filgotinib.
Intervention
NA
Study burden and risks
An overview of risks of study medication and procedures can be found in ICF
Generaal De Wittelaan L11 A3 NA
NA NA
BE
Generaal De Wittelaan L11 A3 NA
NA NA
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Listed location countries
Age
Inclusion criteria
1) Must have the ability to understand and sign a written informed consent form
(ICF), which must be obtained prior to initiation of study procedures
associated with this trial
2) Criterion modified per amendment 9
2.1) Must have enrolled in a CD parent protocol, GS-US-4194015, GS-US-419-4016
or GS-US-419-3895 or any other Gilead/Galapagos-sponsored filgotinib treatment
study for CD
3) Females of childbearing potential must have a negative pregnancy test at Day
1 and must agree to continued monthly pregnancy testing during use of
filgotinib treatment
4) Criterion modified per amendment 9
4.1) Female subjects of childbearing potential who engage in heterosexual
intercourse must agree to use protocol specified method(s) of contraception for
the duration described in the protocol
5) Willingness to refrain from live or attenuated vaccines during the study and
for 12 weeks after last dose of study drug
6) Must have completed all required procedures or met protocol specified
efficacy discontinuation criteria in a prior filgotinib treatment study for CD
Exclusion criteria
1) Subjects who are discontinued from a parent study for reasons other than
disease worsening or lack of response or remission; eg, subjects who
discontinue for safety or tolerability issues are
not eligible for this study
2) Known hypersensitivity to the study drug
3) Any chronic medical condition (including, but not limited to, cardiac or
pulmonary disease, alcohol or drug abuse) that, in the opinion of the
Investigator or Sponsor, would make the subject unsuitable
for the study or would prevent compliance with the study protocol
4) Criterion modified per amendment 9
4.1) Females who may wish to become pregnant and/or plan to undergo egg
donation or egg harvesting for the purpose of current or future fertilization
during the course of the study and for at least 30 days after the last dose of
study drug
5) Criterion deleted per amendment 9
6) Criterion deleted per amendment 9
6.1) Females of reproductive potential who are unwilling to abide by
protocol-specified contraceptive methods as defined in the protocol
7) Use of prohibited concomitant medications as outlined in Section 5.4.2
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 | EUCTR2016-002763-34-NL |
| ClinicalTrials.gov | NCT02914600 |
| CCMO | NL59097.041.17 |