The primary objective of this study is:* To evaluate the effect of filgotinib compared to placebo in active psoriatic arthritis (PsA) as assessed by the American College of Rheumatology 20% improvement (ACR20) response at Week 12Secondary objectives…
ID
Source
Brief title
Condition
- Tendon, ligament and cartilage disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Safety:
Safety will be assessed by the documentation of AEs, physical examinations,
vital signs, and clinical laboratory parameters at specified time points during
the study.
Efficacy:
The primary endpoint is the ACR20 response at Week 12.
Pharmacokinetics:
Plasma concentrations of filgotinib and its primary metabolite (GS 829845) will
be analyzed.
Secondary outcome
Efficacy:
The key secondary endpoints include:
* ACR50 response at Week 12
* Change from Baseline in HAQ DI at Week 12
* Change from Baseline in SF 36v2 physical component summary (PCS) at Week 16
* Change from Baseline in LEI at Week 16, in subjects with enthesitis at
Baseline
* Psoriasis Area and Severity Index 75% improvement (PASI75) response at Week
16, in subjects with psoriasis covering *3% of the BSA at Baseline
* MDA response at Week 16
* Change from Baseline in FACIT Fatigue at Week 16
* Change from Baseline in LDI at Week 16, in subjects with dactylitis at
Baseline
Background summary
This study will test an experimental drug named filgotinib for the treatment of
PsA. PsA is a disease where the body*s immune system attacks its own joints
causing joint pain, swelling and skin inflammation or lesions.
Filgotinib is currently not approved for treatment of any condition. It is
being studied in people with rheumatoid arthritis (RA), inflammatory bowel
disease including ulcerative colitis (UC) and Crohn*s disease (CD) and other
inflammatory diseases involving joints, spine, eye, and kidney.
Study objective
The primary objective of this study is:
* To evaluate the effect of filgotinib compared to placebo in active psoriatic
arthritis (PsA) as assessed by the American College of Rheumatology 20%
improvement (ACR20) response at Week 12
Secondary objectives of this study are:
* To evaluate the effect of filgotinib on core domains of PsA as assessed by
Minimal Disease Activity (MDA) and Very Low Disease Activity (VLDA), ACR
responses, Psoriasis Area and Severity Index including Body Surface Area (PASI
including BSA) responses, Spondyloarthritis Research Consortium of Canada
Enthesitis Index and Leeds Enthesitis Index (SPARCC Enthesitis Index and LEI),
Leeds Dactylitis Index (LDI), Psoriatic Arthritis Disease Activity Score
(PASDAS), Disease Activity Index for Psoriatic Arthritis (DAPSA), Modified Nail
Psoriasis Severity Index (mNAPSI), and Physician*s Global Assessment of
Psoriasis (PhGAP)
* To evaluate the effect of filgotinib on physical function in active PsA as
assessed by Health Assessment Questionnaire * Disability Index (HAQ DI)
* To evaluate the effect of filgotinib on fatigue and quality of life in active
PsA as assessed by Functional Assessment of Chronic Illness Therapy * Fatigue
Scale (FACIT Fatigue), 36-item Short Form Health Survey Version 2 (SF 36v2),
and 12 item Psoriatic Arthritis Impact of Disease (PsAID 12)
* To evaluate the efficacy of filgotinib versus adalimumab in active PsA as
assessed by ACR20 response
* To evaluate the safety and tolerability of filgotinib
See Section 2 of the protocol for full list of study objectives
Study design
The study consists of two parts, the Main Study: Screening through Week 16
(inclusive) and the Long Term Extension (LTE): after Week 16 for 2 years.
After all subjects have completed the Week 16 Visit or have permanently
discontinued the study prior to Week 16, the treatment assignments will be
unblinded to the Sponsor only. The subjects and investigators will remain
blinded to individual level treatment assignment.
Part 1 * Main Study (Screening through Week 16):
Approximately 854 subjects will be randomized in a 2:2:1:2 ratio to one of 4
dosing groups as outlined under Intervention below.
Randomization will be stratified by geographic region and concurrent use of
csDMARD(s) and / or apremilast at randomization (yes or no).
Subjects will be permitted, but are not required, to continue stable doses of
background csDMARD(s), apremilast, and / or NSAIDs. Every effort should be made
to maintain stable background therapy for PsA treatment through the completion
of the Week 16 Visit. Instructions for rescue therapy are detailed in Section
5.4 of the protocol.
Part 2 * LTE (After the Week 16 Visit for 2 years):
After completion of the Main Study, subjects who have not permanently
discontinued study drug will continue on to the LTE as follows:
* Those who were assigned to the filgotinib groups will continue on the same
study drug assignments
* Those who were assigned to the placebo or active comparator groups will be
reassigned 1:1 in a blinded fashion to filgotinib 200 mg or 100 mg once daily
Discontinuation of Study Drug:
For the first 16 weeks of study participation, subjects who temporarily
interrupt or permanently discontinue study drug for any reason are to continue
with study visits and assessments through the Week 16 Visit, per Section 3.5 of
the protocol unless the subject withdraws consent, is lost to follow up, and /
or continued participation in the study is medically contraindicated, per
investigator*s judgment. Study drug interruption and discontinuation
considerations are outlined in Section 3.5 of the protocol. All subjects who
permanently discontinue study drug should continue to receive standard of care
treatment for their PsA including additional therapies, if required.
Discontinuation of Study Participation:
If a subject is unable to complete the study through the Week 16 Visit, and has
received at least one dose of study drug, the subject will complete an Early
Termination (ET) Visit at the time of study discontinuation. Subjects will also
complete a post study follow up visit approximately 4 weeks later (Safety
Follow up Visit).
After the Week 16 Visit, subjects who permanently discontinue study drug for
any reason are to discontinue the study. Subjects who exit the study early,
regardless of dosing duration, are to complete an ET Visit and a Safety Follow
up Visit.
Intervention
Dosing groups in the Main Study:
* Filgotinib 200 mg group: filgotinib 200 mg once daily + placebo to match
(PTM) filgotinib 100 mg once daily + PTM adalimumab subcutaneous (SC) injection
once every two weeks (q2w)
* Filgotinib 100 mg group: PTM filgotinib 200 mg once daily + filgotinib 100 mg
once daily + PTM adalimumab SC injection q2w
* Active comparator group: PTM filgotinib 200 mg once daily + PTM filgotinib
100 mg once daily + adalimumab 40 mg SC injection q2w
* Placebo control group: PTM filgotinib 200 mg once daily + PTM filgotinib 100
mg once daily + PTM adalimumab SC injection q2w
NOTE: All subjects will discontinue adalimumab / PTM injections by the Week 16
Visit (the last injections should be at approximately Week 14).
Dosing groups in the LTE:
* Filgotinib 200 mg group: filgotinib 200 mg once daily + PTM filgotinib 100 mg
once daily
* Filgotinib 100 mg group: PTM filgotinib 200 mg once daily + filgotinib 100 mg
once daily
Study burden and risks
Additional information on filgotinib
The following changes in blood test results were observed in people with
rheumatoid arthritis (RA) taking filgotinib; however, it is currently unknown
if they were caused by the drug:
* Increased creatinine. On average, the values remained within the normal range
even though they increased from when filgotinib was started.
* Increase of (good and bad) fat in the blood. The proportion between bad and
good fat in the blood was generally unchanged. The changes in fat in the blood
were seen within the first 12 weeks of taking filgotinib and did not change
much after then.
In a Phase 2 study among subjects with psoriatic arthritis receiving filgotinib
200 mg once daily for up to 16 weeks, the most frequently reported adverse
effects were common cold, increased level of fat in the blood, and increased
level of an enzyme called gamma-glutamyl transferase in the blood. The enzyme
is normally present in many organs throughout the body, with the highest level
found in the liver. The body may release it in response to damage or disease
mostly to the liver or bile ducts. In this study, one subject who received
filgotinib had serious adverse effect of pneumonia and died.
Other possible risks while taking filgotinib:
- Infections, including serious infections (some with fatal outcome).
- Tuberculosis has more often been seen in people with weakened immune system.
- Certain types of vaccines should not be given prior to and during treatment
with filgotinib. The study doctor will discuss this with the patient.
- Drugs that affect the immune system may increase the risk of cancer. It is
currently not possible to know whether taking filgotinib increases your risk of
getting cancer.
Some adverse effects were observed in animals and are summarized below:
Filgotinib treatment caused malformations (birth defects) of the bone and
internal organs in the foetuses of pregnant rats and rabbits. These birth
defects happened at doses producing blood levels of filgotinib comparable to
blood levels produced by the planned doses in study participants in this study.
Other effects were also seen, including increased pregnancy loss and decreased
foetal body weights.
Based on these animal data, filgotinib may cause birth defects in humans. To be
in this study, highly effective birth control is required for both men and
women. Birth control should also be considered for female partners of male
participants.
Filgotinib caused damage to the testes (testicles) of male rats and dogs. In
these animals, filgotinib caused deterioration and loss of cells that make
sperm, resulting in less sperm, or no sperm being produced. As a result,
filgotinib caused male rats to be infertile.
Damage to the testes in rats and dogs was observed at doses producing blood
levels of filgotinib slightly higher than blood levels produced by the planned
doses in study participants in this study. At these doses, while sperm counts
in rats and dogs increased after filgotinib was stopped, they stayed low
overall and did not return to normal. At the highest doses tested in male rats
and dogs, these adverse effects did not go away. These adverse effects were not
seen in the testes of rats and dogs when these animals were given a dose that
produces blood levels of filgotinib similar to blood levels produced by the 200
mg daily dose in humans.
Based on the results in male rats and dogs, there is a risk that men treated
with filgotinib may have reduced sperm production and may become temporarily or
permanently infertile. Two additional separate studies are ongoing in men to
measure the effect of filgotinib on sperm production. Until results from that
study are available, the long-term effect of filgotinib on sperm production in
humans is unknown.
As with any drug, there are unknown risks involved, since only a limited number
of people have taken this drug and not all adverse effects or risks of taking
this drug are known. In the future, more serious and/or long-term adverse
effects could happen, including allergic reactions. Also, the risks or
discomforts described here could happen more often or be more severe than what
has been seen before.
Additional information on adalimumab (HUMIRA®)
Some uncommon, but potentially serious or life-threatening events seen in
patients taking adalimumab include:
* Infections of the brain and the protective membranes covering the brain
* Opportunistic infections (rare infections that only occur in individuals with
a weakened immune system)
* Tuberculosis
* Cancer
* Stroke
* Myocardial infarction (heart attack)
* Arrhythmia (irregular heartbeat)
* Heart failure
* Aortic aneurism (abnormal blood vessel enlargement)
* Pulmonary embolism (blood clot in the lung)
* Reaction at the site of injection (e.g. swelling, itching, stinging,
tenderness)
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Listed location countries
Age
Inclusion criteria
* Male or female subjects who are 18 75 years of age (19-75 years of age at
sites in Republic of Korea, 20 75 years of age at sites in Japan and Taiwan) on
the day of signing initial informed consent
* Meet Classification Criteria for Psoriatic Arthritis (CASPAR) and have a
history consistent with PsA *6 months at Screening
* Have active PsA defined as *3 swollen joints (from a 66 swollen joint count
[SJC]) and *3 tender joints (from a 68 tender joint count [TJC]) at Screening
and Day 1; these may or may not be the same joints at Screening and Day 1
* Must have a documented history or active signs of at least one of the
following at Screening:
a) Plaque psoriasis
b) Nail changes attributed to psoriasis
* Have had inadequate response or intolerance to *1 csDMARD, apremilast and /
or NSAID, administered over the course of *12 weeks for the treatment of PsA,
as per local guidelines / standard of care
* If continuing csDMARD(s) during the study, subjects are permitted to use only
a maximum of 2 of the drugs as outlined in Section 4.2 and must have been on
this treatment for *12 consecutive weeks prior to Screening, with a stable dose
and route of administration (defined as no change in prescription) for *4 weeks
prior to Day 1
* Concomitant NSAIDs or corticosteroids are permitted as specified in Sections
4.2 and 4.3 of the protocol.
For a complete list of study inclusion criteria, please refer to Section 4.2 of
the protocol.
Exclusion criteria
* Prior PsA or psoriasis treatment with a bioDMARD
* Prior exposure to a JAK inhibitor >2 doses
* Any active / recent infection, as specified in Section 4.3 in the protocol
* Any chronic and / or uncontrolled medical condition that would put the
subject at increased risk during study participation or circumstances which may
make a subject unlikely or unable to complete or comply with study procedures
and requirements, per investigator judgement
* Any moderately to severely active musculoskeletal or skin disorder other than
PsA or plaque psoriasis that would interfere with assessment of study
parameters, as per judgement of investigator
NOTE: Prior history of reactive arthritis or axial spondyloarthritis is
permitted if there is documentation of change in diagnosis to PsA or additional
diagnosis of PsA
* Any history of an inflammatory arthropathy with onset before age 16 years old
* Active autoimmune disease that would interfere with assessment of study
parameters or increase risk to the subject by participating in the study (e.g.
uveitis, inflammatory bowel disease, uncontrolled thyroiditis, systemic
vasculitis, transverse myelitis), per judgement of investigator
* Presence of any extra articular manifestations typically associated with
rheumatoid arthritis (RA), such as rheumatoid nodules, rheumatoid lung, or
other signs / symptoms, as per judgement of investigator
* Pregnancy or nursing females
* Active drug or alcohol abuse, as per judgement of investigator
* Unwilling or unable to follow protocol requirements
For a complete list of study exclusion criteria, please refer to Section 4.3 of
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 | EUCTR2019-001996-35-NL |
| ClinicalTrials.gov | NCT04115748 |
| CCMO | NL70851.028.20 |