A MULTICENTER, OPEN-LABEL EXTENSION STUDY TO
ASSESS THE LONG-TERM SAFETY, TOLERABILITY, AND
EFFICACY OF BIMEKIZUMAB IN THE TREATMENT OF STUDY
PARTICIPANTS WITH ACTIVE AXIAL SPONDYLOARTHRITIS,
ANKYLOSING SPONDYLITIS, AND NONRADIOGRAPHIC AXIAL
SPONDYLOARTHRITIS

axSpA epidemiology Axial SpA is a chronic inflammatory disease that impacts a
substantial proportion of the population. Limited evidence exists regarding the
global occurrence of axSpA with a prevalence of 0.20 to 0.25% in Europe and
North America, and a wider range in Asia (0.06 to 0.20%) (Stolwijk et al,
2016); however, recent data suggest that the prevalence is similar to that of
RA in the US (axSpA: 0.7% to 1.4%; RA: 0.5% to 1.0%) (Reveille et al, 2012;
Myasoedova et al, 2010; Helmick et al, 2008). Axial SpA comprises those
diseases with mainly axial involvement (sacroiliac joints and spine), including
AS and nr-axSpA. Current treatments for axSpA Nonsteroidal anti-inflammatory
drugs are used as first-line treatment and are effective for the symptoms (pain
and stiffness) of axSpA (van der Heijde et al, 2017; Ward et al, 2015;
Poddubnyy, 2013; Poddubnyy et al, 2012), but many patients lose or never have
clinically meaningful response and structural damage often progresses despite
their use. Conventional disease-modifying antirheumatic drugs (DMARDs, eg,
methotrexate [MTX] and sulfasalazine [SSZ]) have no proven efficacy in axial
disease, but may benefit patients with peripheral joint disease (Haibel et al,
2007; Braun et al, 2006; Haibel et al, 2005). Therefore, DMARDs are recommended
only in patients with predominantly peripheral manifestations (Braun et al,
2011). Patients who are intolerant of or have inadequately responded to NSAIDs,
or those in whom NSAIDs are contraindicated, have approved treatment options
such as tumor necrosis factor alpha (TNFα) inhibitors (van der Heijde, 2017;
Ward et al, 2015). Recently, the interleukin (IL)-17 cytokine family has been
identified as a therapeutic target in axSpA and secukinumab, an IL-17A
monoclonal antibody, has recently been approved as a treatment option in active
AS. Bimekizumab Bimekizumab (UCB4940) is an engineered, humanized full-length
monoclonal antibody of IgG1 subclass of approximately 150,000 Dalton, which is
expressed in a genetically engineered Chinese Hamster Ovarian (CHO) cell line.
Bimekizumab has high affinity for human IL-17A and human IL-17F and selectively
and potently inhibits the activity of both isoforms in vitro. Interleukin-17A
and IL-17F are key proinflammatory cytokines believed to play important roles
in autoimmune and inflammatory diseases. Therefore, bimekizumab permits an
evaluation of the potential for additional efficacy, which may be conferred by
dual inhibition of both cytokines, in patients suffering from diseases in which
both cytokines are active. Bimekizumab is being developed for the treatment of
patients with inflammatory diseases such as PsA, psoriasis (PSO), and axSpA.

The primary objective of this open-label extension (OLE) study is to assess the
long-term safety and tolerability of bimekizumab administered over a period of
up to 112 weeks.

This is a multicenter, OLE study to assess the long-term safety, tolerability,
and efficacy of bimekizumab for a Treatment Period of up to 112 weeks in adult
study participants with axial spondyloarthritis (axSpA; radiographic and
nonradiographic) who completed either of the Phase 3 studies, AS0010 or AS0011.
The study will include a Study Entry Visit (at Week 52 of AS0010 and AS0011), a
Treatment Period (up to 112 weeks), and a Safety Follow-Up (SFU) Visit (20
weeks after the final dose of bimekizumab). The maximum study duration per
subject will be 128 weeks.
At Week 52 of AS0010 and AS0011, eligible study participants may be enrolled
into AS0014 to continue to receive bimekizumab treatment. These study
participants will complete the Week 52 study assessments and any additional
AS0014 Entry Visit assessments and will receive their first dose of extension
treatment of bimekizumab in AS0014.
During the Treatment Period, study participants will attend study visits every
4 weeks for the first 4 visits and then every 12 weeks (Week 16 and onwards)
for study assessments and administration of bimekizumab (if applicable) by
study site staff. The dose of bimekizumab administered in AS0014 will be 160mg
every 4 weeks (Q4W) by subcutaneous (sc) injection, which is the same dosing of
the bimekizumab groups in the feeder studies. At interim visits, study
participants may be allowed self-administration at home per the discretion of
the Investigator and study participant, after training by the site.
Following study completion or early withdrawal from the Treatment Period, study
participants will return for an SFU Visit 20 weeks after their final dose of
bimekizumab. Study participants meeting the withdrawal criteria will undergo
the Early Termination (ET) Visit assessments and will enter the SFU Visit.

Treatment(s), dose(s), mode of administration, and duration:

All study participants will receive bimekizumab 160mg Q4W sc upon entry into
AS0014.
The minimum time between doses should be no less than 21 days and no more than
35 days for Q4W dosing.
The study participant will receive a single injection at the clinical site or
may self-administer it at home at specified study visits. Study participants
who are unable to or decide not to self administer or those without a family
member/friend/caregiver (or appropriate designee) who can help, may continue to
visit the site for investigational medicinal product (IMP) administration only.
If administered at home, the study participant/caregiver (or appropriate
designee) will document the date, body location, and time point of
administration of IMP.
Suitable areas for sc injections are the lateral abdominal wall, upper outer
thigh, and upper arm if the IMP is injected by a healthcare provider or a
caregiver. Injection sites should be rotated and injections should not be given
into areas where the skin is tender, bruised, red, or hard. It is also
acceptable to inject in the upper arm if the preferred areas of the abdomen or
thigh are covered in lesions, tender, or bruised.
An IMP Handling Manual will be provided to each site containing instructions
regarding drug preparation and dosing.

The study drug may have side effects. In addition, the study drug may involve
risks that are currently unknown. In the data from the completed studies, most
of the side effects were mild to moderate, easily manageable, resolved, and did
not require discontinuation of the treatment. These side effects included:
Very Common (occurring in more than 1 in 10 of study participants):
* Common colds and runny nose, which were all mild or moderate
Common (occurring in 1 in 10 of study participants):
* Less blood cells that help to fight infections, called neutrophils
* Diarrhea
* Fungal infections of the skin or mucous membranes, mostly in the mouth. For
example, if you develop symptoms of a fungal infection, particularly in the
mouth or throat (creamy white bumps or patches on your tongue, inner cheeks,
gums or throat; bad taste in your mouth; pain or difficulty while swallowing),
you must tell your study doctor immediately so appropriate action can be
discussed.
* Increase in enzymes made by the liver that could indicate liver problems. If
this happens to you during the study, extra testing of blood and urine will be
done to try and understand the cause and best treatment for this.
* Sore throat
* Joint pain
* Skin irritation such as red, itchy, dry, cracked skin
You may have an allergic reaction to the study drug. Although serious allergic
reactions have not yet been seen in the participants receiving this study drug,
signs may include a skin rash, swelling of the face, tongue, lips, or throat,
or having trouble breathing. If you have any of these signs, you must go to an
emergency department immediately and make sure that your study doctor is
informed.
Infections can occur and in rare cases might become serious. You must tell your
study doctor if you develop signs of infection, for example: persistent fever,
diarrhea, flu-like symptoms, red or painful skin, feeling short of breath, ear
pain with discharge or cough which will not go away, so that you can be
assessed and treated appropriately.
If you are diagnosed with inflammatory bowel disease (ulcerative colitis or
Crohn*s disease) or have a disease flare (with symptoms such as persistent
bloody diarrhea with urgency or crampy abdominal pain) these complaints might
become worse during the study. You must tell your study doctor immediately so
appropriate action can be discussed.

Uncommon (occurring in more than 1 in 1000 and less than 1 in 100 of the
patients)
* Swelling, redness, or pain at the site where the study drug was injected.
* Allergic reactions or symptoms such as rash, which might take a few days to
develop.

What are the other possible risks of taking part?
* Vital signs recording: An inflatable cuff will be placed on your arm and a
machine will measure your blood pressure and pulse rate, after you have been
sitting down for 5 minutes. You may experience mild discomfort in your arm
while the cuff is inflated.
* Venous blood samples: Throughout the study, a maximum of 20mL (approximately
1 to 2 tablespoons of blood) will be taken per visit. A total of 173mL (about
half of what you give during blood donation) will be taken throughout the study.
During the collection of blood samples, you may experience slight discomfort
and a small amount of bleeding, discoloration, or bruising at the site where
the needle was inserted. Clot formation and infections may occur at the
puncture site, but this is extremely rare. Fainting may occur during or shortly
after having blood drawn. If faintness is experienced, you should lie down
immediately to avoid possible injury caused by falling and notify the site
research staff. In very rare cases nerve damages may occur.
* Subcutaneous (under the skin) injection and injection site reactions: For
most people, needle punctures for injections do not cause any serious problems.
Sometimes they may cause bleeding or bruising where the injection is given.
Sometimes people complain of discomfort and/or pain at the site of the
injection. Rarely, injections may cause skin and/or soft tissue infections.
Additionally, if a blood vessel is entered by the needle, the risk of infection
could include germs entering into the blood system, which can be very serious.
The risk of this happening is low.
* ECG: You will be requested to disrobe from the waist up in order to ensure
correct ECG recording. You may experience slight skin irritation from the
adhesive on the ECG electrodes, but this is generally mild and clears up within
a few days.
* X-ray - Sacroiliac joint and spine (depending on whether you participated in
AS0010 or AS0011 study prior to this study): You will be exposed to a low level
of radiation. You must not have an X-ray if you think you could be pregnant.
Please inform your study doctor accordingly.
* Mental health problems and/or depression: Some patients who have axSpA suffer
from psychological problems like depression. You will be asked to complete
questionnaires at all visits about how you are feeling mentally and if you have
had any thoughts of hurting yourself during the study to monitor your mental
health status. You may be asked to follow up with a mental health professional
based on the results of these questionnaires. Tell the study doctor if you feel
important changes in your mood or if you experience psychological problems.
* Vaccines: Please tell your study doctor if you are planning to get
vaccinated, as some types of vaccinations are not allowed prior to dosing,
during the study and for up to 20 weeks after the last dose of the study drug.
* Private medical insurance: If you hold private medical insurance, you are
advised to check with the company who provides this insurance before agreeing
to take part. This is to make sure that your medical insurance will not be
affected by being in a clinical study.
The risk associated with having an MRI of the spine and joints is very minimal.
However, if you are claustrophobic (have a fear of closed spaces) or have had
any metal placed in your body (for example, during a surgery), you should tell
your doctor.