3.1 Primary objectiveThe primary objective of the study is to evaluate the efficacy of bimekizumab administered scQ2W for 12 weeks compared to CZP in the treatment of subjects with active AS.3.2 Secondary objectivesThe secondary objectives of the…
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Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary efficacy variable for this study is as follows:
*Change from Baseline in ASDAS at Week 12
Secondary outcome
The secondary efficacy variables for this study are as follows:
*ASDAS-ID at Week 12
*ASDAS-MI at Week 12
Assessment time points for the other efficacy variables are specified in Table
5*1. Other efficacy
variables are as follows:
*Change from Baseline in ASDAS
*ASAS20 response
*ASAS40 response
*Time to ASAS20 response
*Time to ASAS40 response
*ASAS partial remission
*Change from Baseline in BASDAI
*Changes in bone formation as measured by standardized uptake value by area
under the curve (SUVauc) and derived from PET-MRI or PET-CT at Baseline, week
12 and week 52.
The primary safety variables for this study are as follows:
*Incidence of AEs and SAEs
*Adverse events leading to withdrawal from IMP
The other safety variables for this study are as follows:
*Change from Baseline in vital signs (blood pressure, temperature, pulse rate)
and body
weight
*Change from Baseline in physical examination
*Change from Baseline in standard 12-lead electrocardiogram (ECG) intervals
(RR, PR, QRS,
QT, and QT intervals corrected for heart rate using Fridericia*s formula [QTcF])
*Change from Baseline in clinical laboratory values (hematology, biochemistry,
and
urinalysis)
The PK variables are plasma concentrations of bimekizumab and CZP.
The PD variables assessed at time points specified in Table 5*1 are the blood
or blood derivative
(eg, plasma) concentrations of cytokines and chemokines of relevance to
IL-17A/F signaling
pathway, TNF signaling pathway, AS biology, and bone metabolism. Additional
variables may
include, but will not be limited to, serum complement concentrations and
mononuclear cell
subtypes
Immunological variables will allow evaluation of immunogenicity as well as
immunological
biomarkers. Anti-bimekizumab antibody and anti-CZP antibody detection prior to
and following
study treatment will be evaluated.
Where local regulations permit, blood and urine will be collected at specific
time points specified
in Table 5*1 and stored for up to 20 years to allow for potential exploratory
analyses of
ribonucleic acid (RNA), proteins, and metabolite biomarkers relevant to AS,
bone metabolism.
and the inflammatory and immune response processes. The nature and format of
these tentative
analyses will be determined at a later stage.
Additional blood samples will be collected from subjects who consent to
participate in the
pharmacogenetic substudy at specific time points specified in Table 5*1 and
stored at -80°C for
up to 20 years. Pharmacogenetic biomarkers may be measured to evaluate the
relationship to
response to treatment with bimekizumab, AS disease biology, bone metabolism, and
inflammatory and immune response processes. The nature and format of these
tentative
sub-study analyses will be determined when the results of the main study are
made available.
Background summary
This is a Phase 2a, multicenter, randomized, subject-blind, investigator-blind,
parallel-group,
study to investigate the efficacy and safety of bimekizumab (also known as
UCB4940) and
certolizumab pegol ([CZP]; Cimzia® ) in adult subjects with active ankylosing
spondylitis (AS).
Eligible subjects will have active AS, determined by documented radiologic
evidence (X-ray)
fulfilling the Modified New York criteria for AS (van der Linden et al, 1984),
including
symptoms for *3 months and age of onset <45 years. Furthermore, subjects will
have moderate
to severe active disease at Screening (Bath Ankylosing Spondylitis Disease
Activity Index
[BASDAI] *4 and spinal pain *4 [BASDAI Question 2]).
The primary objective of the study is to evaluate the efficacy of bimekizumab
administered
subcutaneously (sc) every 2 weeks (Q2W) for 12 weeks compared to CZP in the
treatment of
subjects with active AS. The primary efficacy variable is the change from
Baseline in
Ankylosing Spondylitis Disease Activity Score (ASDAS) at Week 12.
The secondary objectives of the study is to assess the safety and tolerability
of bimekizumab.
The secondary efficacy variables include the determination of ASDAS inactive
disease (ASDAS-ID) at Week 12 and ASDAS major
improvement (ASDAS-MI) at Week 12.
Primary safety variables include the incidence of adverse events (AEs) and
serious adverse events (SAEs).
Other exploratory objectives of the study are to evaluate the effect of
bimekizumab or CZP on changes in bone formation, and to assess the
pharmacokinetics (PK) and immunogenicity of bimekizumab, to assess additional
biomarker, clinical, and imaging data as available and to assess the efficacy
and safety of bimekizumab or CZP during the Treatment Extension Period.
Multiple sites in North America, Europe, and the Asian-Pacific (APAC) region
will randomize
approximately 60 subjects in a 2:1 ratio to receive either bimekizumab or CZP.
The study consists of a Screening Period (2 to 4 weeks), Treatment Period (12
weeks), Treatment
Extension Period (36 weeks), and a Safety Follow-up (SFU) Period (20 weeks
after the final
dose of the investigational medicinal product [IMP]). Therefore, the maximum
duration of the
study is 68 weeks. For the subgroup of subjects at selected sites that take
part in imaging
assessments of the spine and have a PET-MRI or PET-CT scan at Week 52, the
duration of the
Treatment Extension Period is extended to 40 weeks and the maximum duration of
the study to
72 weeks.
Screening Period
The Screening Period will last for a minimum of 2 weeks and up to 4 weeks.
During the
Screening Period, the Investigator will assess the eligibility of subjects
according to the inclusion
and exclusion criteria. The Screening Period will also enable washout of any
medications not
permitted for use during the study.
Treatment Period
At Baseline/Day 1, subjects will be randomized in a 2:1 ratio to receive the
following blinded
study treatments during the Treatment Period:
*Bimekizumab 160mg sc Q2W from Week 0 through Week 10. In addition, subjects
will
receive 1 placebo injection at Baseline (Visit 2), Week 2 (Visit 3), and Week 4
(Visit 4) in
order to maintain the blind vs the certolizumab pegol (CZP) loading dose at
these visits.
*Certolizumab pegol 400mg sc Q2W at Weeks 0, 2, and 4 (loading dose) followed
by CZP
200mg sc Q2W in Weeks 6 to 10.
The IMP will be administered sc in the clinic by trained site personnel.
Treatment Extension Period
After completing the 12-week Treatment Period, subjects will enter a 36-week
Treatment
Extension Period (or 40-week for the subgroup of subjects with PET-MRI or
PET-CT in this
study period) and will receive the following treatments:
*Subjects randomized to bimekizumab during the Treatment Period will receive
bimekizumab
320mg sc every 4 weeks (Q4W) from Week 12 to Week 44 (or Week 48 for the
subgroup of
subjects with PET-MRI or PET-CT in this study period).
*Subjects randomized to CZP during the Treatment Period will receive CZP 400mg
Q4W
from Week 12 to Week 44 (or Week 48 for the subgroup of subjects with PET-MRI or
PET-CT in this study period).
Subjects not responding to treatment will be withdrawn from the study as per
Investigator*s
discretion.
Safety Follow-Up Period
All subjects who complete the study or who discontinue early, including those
withdrawn from
study treatment, will have a SFU Visit at 20 weeks after their final dose of
IMP.
Study objective
3.1 Primary objective
The primary objective of the study is to evaluate the efficacy of bimekizumab
administered sc
Q2W for 12 weeks compared to CZP in the treatment of subjects with active AS.
3.2 Secondary objectives
The secondary objectives of the study is as follows:
* To assess the safety and tolerability of bimekizumab.
3.3 Other objectives
The other objectives of the study are as follows:
*To assess additional biomarker, clinical, and imaging data as available
*To assess the efficacy and safety of bimekizumab or CZP during the Treatment
Extension
*To evaluate the effect of bimekizumab or CZP on changes in bone formation
*To assess the PK and immunogenicity of bimekizumab
*To assess the efficacy and safety of bimekizumab or CZP during the Treatment
Extension Period.
Study design
This is a Phase 2a, multicenter, randomized, subject-blind, investigator-blind,
parallel-group,
study to investigate the efficacy and safety of bimekizumab (also known as
UCB4940) and
certolizumab pegol ([CZP]; Cimzia® ) in adult subjects with active ankylosing
spondylitis (AS)
Intervention
The IMPs used in this study are bimekizumab and CZP.
Bimekizumab will be supplied as a clear to opalescent, colorless to slightly
brown, sterile,
preservative-free solution in 2mL Type I, colorless glass vials (1.0mL
extractable volume) closed
with a rubber stopper and sealed with an aluminum cap overseal. Each single-use
dose vial will
contain 160mg/mL bimekizumab in 55mM sodium acetate, 220mM glycine and 0.04%
(w/v)
polysorbate 80 at pH 5.0.
Certolizumab pegol will be supplied as a sterile, clear, colorless-to-slightly
yellow solution at
pH 4.7 in 1mL single-use glass pre-filled syringes (PFS) for sc injection. Each
syringe contains
an extractable volume of 1.0mL at a concentration of CZP 200mg/mL in 10mM
sodium acetate
buffer and 125mM sodium chloride as a tonicity agent. The syringes are stored
at 2 to 8ºC, not
frozen, and protected from light.
Placebo will be supplied as 0.9% sodium chloride aqueous solution
(physiological saline,
preservative free) of pharmacopoeia (United States Pharmacopoeia/European
Pharmacopoeia)
quality appropriate for injection.
Further details of the IMPs and their specifications are provided in the IMP
Handling Manual.
Study burden and risks
In the 4 studies done to date with bimekuzimab, most of the side effects were
mild, easily manageable, and did not require discontinuation of the treatment.
These side effects included:
* Infections (mostly common colds) and sore throats, all mild or moderate in
severity
* Transient decrease in neutrophil count (a type of white blood cells) that
helps to fight infections).
* Transient decrease in the hemoglobin, the iron-carrying component of red
blood cells (anemia).
* Changes in blood values that could indicate liver problems. In case this
happens to you during the study, extra testing of blood and urine will be done
to try and determine possible other causes of this.
* Gastrointestinal disturbances, like mouth ulcers (sores), abdominal pain
(lower stomach pain), abdominal distension (stomach bloating), nausea,
vomiting, flatulence (passing gas), and diarrhea. These got better without any
specific treatment.
* Mild swelling, mild redness, or mild or moderate pain at the site where the
study drug was injected.
* Dizziness and headache.
* Fatigue (feeling tired).
You should immediately contact the investigator and go to an Emergency
Department if you have an allergic reaction to the study drug. Signs may
include a severe rash, a swollen face, 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. To date, no subjects in studies have
had allergic reactions to bimekizumab.
What side effects are known for certolizumab pegol
Common (may affect up to 1 in 10 people):
* bacterial infections in any site (a collection of pus)
* viral infections (including cold sores, shingles, and influenza)
* fever
* high blood pressure
* rash or itching
* headaches (including migraines)
* sensory abnormalities such as numbness
* tingling
* burning sensation
* feeling weak and generally unwell
* pain
* blood disorders
* liver problems
* injection site reactions
* nausea
Side Effects of certolizumab pegol
Prevalence Side Effects
Up to 1 in 10 people * bacterial infections in any site (a collection of pus),
* viral infections (including cold sores, shingles, and influenza),
* fever,
* high blood pressure,
* rash or itching,
* headaches (including migraines),
* sensory abnormalities such as numbness,
* tingling,
* burning sensation,
* feeling weak and generally unwell,
* pain,
* blood disorders,
* liver problems,
* injection site reactions,
* nausea
Up to 1 out of 100 * allergic conditions including allergic rhinitis and
allergic reactions to the medicine (including anaphylactic shock),
* antibody directed against normal tissue,
* blood and lymphatic system cancers like lymphoma and leukemia,
* solid organ cancers,
* skin cancers,
* pre-cancerous skin lesions,
* benign (non-cancerous) tumors and cysts (including those of the skin),
* heart problems including weakened heart muscle, heart failure, heart attack,
chest discomfort or chest pressure, abnormal heart rhythm including irregular
heartbeats,
* edema (swelling in the face or legs),
* lupus (immune/connective tissue disease) symptoms (joint pain, skin rashes,
photosensitivity and fever),
* inflammation of the blood vessels,
* sepsis (serious infection which can result in organ failure, shock or death),
* tuberculosis infection,
* fungal infections (occur when the ability to fight off infection is
lessened),
* respiratory disorders and inflammation (including asthma, shortness of
breath, cough, blocked sinuses, pleurisy, or difficulty breathing),
* stomach problems including abdominal fluid collection, ulcers (including oral
ulcers), perforation, distension, inflammation heartburn, upset, dry mouth,
bile problems,
* muscle problems including increased muscle enzymes, changes in blood levels
of different salts,
* changes in cholesterol and fat levels in the blood, blood clots in the veins
or lungs,
* bleeding or bruising,
* changed numbers of blood cells, including low red cell count (anemia), low
platelet counts, increased platelet counts,
* swollen lymph nodes,
* flu-like symptoms, chills, altered temperature perception, night sweats,
flushing,
* anxiety and mood disorders such as depression, appetite disorders, weight
change,
* ringing in the ears,
* vertigo (dizziness),
* feeling faint, including loss of consciousness,
* nerve disorders in the extremities including symptoms of numbness, tingling,
burning sensation, dizziness, tremor,
* skin disorders such as new onset or worsening of psoriasis, inflammation of
the skin (such as eczema), sweat gland disorders, ulcers, photosensitivity,
acne, hair loss, discoloration, nail separation, dry skin and injuries,
impaired healing,
* kidney and urinary problems including impairment of kidney function, blood in
the urine and urinary disturbances,
* menstrual cycle (monthly period) disorders including lack of bleeding, or
heavy or irregular bleeding, breast disorders,
* eye and eyelid inflammation, vision disturbances, problems with tears,
* some blood parameters increased (blood alkaline phosphatase increased),
prolonged coagulation (clotting) test times.
Fewer than 1 out of 100 subjects (up to 1 in 1000) * gastrointestinal cancer,
melanoma,
* lung inflammation (interstitial lung disease, pneumonitis),
* stroke,
* blockage in blood vessels (arteriosclerosis),
* poor blood circulation which makes the toes, and fingers numb and pale
(Raynaud*s phenomenon), mottled purplish skin discoloration, small veins near
the surface of the skin may become visible,
* pericardial inflammation,
* cardiac arrhythmia,
* enlarged spleen,
* increase of red cell mass, white blood cell morphology abnormal, formation of
stones in the gall bladder, kidney problems (including nephritis),
* immune disorders such as sarcoidosis (rash, joint pain, fever), serum
sickness, inflammation of the fat tissue,
* angioneurotic oedema (swelling of the lips, face, throat),
* thyroid disorders (goitre, tiredness, weight loss),
* increased iron levels in the body, increased blood levels of uric acid,
* suicide attempt, mental impairment, delirium,
* inflammation of the nerves for hearing, seeing, or of the face,
* impaired coordination or balance,
* increased gastrointestinal motility, fistula (tract from one organ to
another) (any site),
* oral disorders including pain on swallowing,
* skin sloughing, blistering,
* hair texture disorder,
* sexual dysfunction,
* seizure.
* worsening of a muscle disease known as dermatomyositis*,
* Stevens-Johnson syndrome*,
* a skin reaction known as erythema multiforme*.
Other Not known (frequency cannot be estimated from the available data):
multiple sclerosis*, Guillain-Barré syndrome*, Merkel cell carcinoma (a type of
skin cancer)*.
*These events have been related to this class of medicines but the incidence
with certolizumab pegol is not known. Certolizumab pegol is stored with a latex
cap over the needle. Therefore, there is also a small risk of an allergic
reaction due to the latex.
Allée de la Recherche 60
Brussels 1070
NL
Allée de la Recherche 60
Brussels 1070
NL
Listed location countries
Age
Inclusion criteria
To be eligible to participate in this study, all of the following criteria must
be met:
1. An Institutional Review Board (IRB)/Independent Ethics Committee (IEC)
approved written
Informed Consent form is signed and dated by the subject.
2. Subject is considered reliable and capable of adhering to the protocol (eg,
able to understand
and complete diaries), visit schedule, and medication intake according to the
judgment of the
Investigator.
3. Subject is male or female and at least 18 years of age.
4. Subject has a documented diagnosis of adult-onset AS as defined by
documented radiologic
evidence (X-ray) fulfilling the Modified New York criteria for AS (1984) of at
least
3 months* symptom duration and age of onset <45 years.
5. Subject has moderate to severe active disease at the Screening Visit as
defined by each of the
following:
*BASDAI score *4
*Spinal pain score *4 on a 0 to 10 numeric rating scale (NRS) (from BASDAI Item
2)
6. Subject must have had an inadequate response to, have a contraindication to,
or has been
intolerant to at least 2 NSAIDs (inadequate response to an NSAID is defined as
lack of
response to at least 14 days of continuous NSAID therapy at the highest
tolerated dose of the
administered NSAID).
7. Subject may not have been exposed to more than 1 TNF antagonist prior to the
Baseline Visit
and may not be a primary failure to any TNF antagonist therapy (defined as no
response
within the first 12 weeks of treatment with the TNF antagonist.
8. Subject has hs-CRP levels above the ULN at the Screening Visit. One re-test
of hs-CRP is
permitted during the Screening Period upon discretion of the Investigator.
9. Female subjects must be postmenopausal (at least 1 year; to be confirmed
hormonally as part
of the screening process, if less than 2 years since last menstrual period),
permanently
sterilized (eg, tubal occlusion, hysterectomy, bilateral salpingectomy) or, if
of childbearing
potential (and engaged in sexual activity that could result in procreation),
must be willing to
use a highly effective method of contraception up till 20 weeks after last
administration of
IMP, and have a negative pregnancy test at Visit 1 (Screening) and immediately
prior to first
dose. The following methods are considered highly effective when used
consistently and
correctly.
*combined (estrogen and progestogen) hormonal contraception associated with
inhibition
of ovulation (oral, intravaginal or transdermal)
*progestogen-only hormonal contraception associated with inhibition of
ovulation (oral,
injectable, implantable)
*intrauterine device (IUD)
*intrauterine hormone-releasing system (IUS)
*bilateral tubal occlusion
*vasectomized partner (where postvasectomy testing had demonstrated sperm
clearance)
*sexual abstinence if it is in accordance with a subject*s preferred and common
lifestyle.
Subjects who use abstinence as a form of birth control must agree to abstain
from
heterosexual intercourse until 20 weeks after the final dose of IMP
(anticipated 5
half-lifes of bimekizumab). Study personnel must confirm the continued use of
abstinence is still in accordance with the subject*s lifestyle at regular
intervals during the
study.
Male subjects with a partner of childbearing potential must be willing to use a
condom when
sexually active, up until 20 weeks after the last administration of IMP
(anticipated 5 halflives).
Exclusion criteria
Subjects are not permitted to enroll in the study if any of the following
criteria is met:
1. Female subject who is breastfeeding, pregnant, or planning to become
pregnant during the
study or within 20 weeks following final dose of study drug. Male subject who
is planning a
partner pregnancy during the study or within 20 weeks following the final dose.
2. Subject who has previously received bimekizumab or CZP.
3. Subject has participated in another study of a medication under
investigation within the last 3
months or at least 5 half-lives of the IMP, whichever is greater, or is
currently participating in
another study of a medication under investigation.
4. Subject has a known hypersensitivity to any excipients of bimekizumab or CZP.
5. Subject has received previous treatment with a polyethylene glycolylated
(PEGylated)
compound that resulted in a severe hypersensitivity reaction or an anaphylactic
reaction
6. Subject has a total ankylosis of the spine or a diagnosis of any other
inflammatory arthritis
eg, RA, systemic lupus erythematosus, sardoidosis, psoriatic arthritis, or
reactive arthritis.
Subjects with a diagnosis of Crohn*s disease or ulcerative colitis are allowed
as long as they
have no active symptomatic disease at Screening or Baseline.
7. Subject has a secondary, noninflammatory condition (eg, osteoarthritis,
fibromyalgia) that in
the Investigator*s opinion is symptomatic enough to interfere with evaluation
of the effect of
study drug on the subject*s primary diagnosis of active AS.
8. Subject has received previous or current biological treatment other than
TNF* inhibitor
treatment.
9. Subjects must not have used medications
10. Subject has:
*a history of chronic or recurrent infections (eg, more than 3 episodes
requiring systemic
antibiotics or antivirals during the preceding year). Minor illnesses like
common cold or
transient, localized infections that may have been treated with a short course
of antibiotic
therapy (up to 7 days) need not count in this assessment.
*a serious or life-threatening infection within the 6 months prior to the
Baseline Visit
(including herpes zoster) or hospitalization for any infection in the last 6
months.
*any current sign or symptom that may indicate an active infection (except for
common
cold), or has had an infection requiring systemic antibiotics within 2 weeks
prior to
Baseline.
*a high risk of infection in the Investigator*s opinion (eg, subjects with leg
ulcers,
indwelling urinary catheter, prior prosthetic joint infection at any time,
subjects who are
permanently bedridden or wheelchair assisted).
11. Subject has a history of or current clinically active infection with
Histoplasma, Coccidiodes,
Paracoccidioides, Pneumocystis, nontuberculous mycobacteria (NTMB),
Blastomyces, or
Aspergillus or current active Candidiasis (local or systemic)
12. Subject has acute or chronic viral hepatitis B or C or human
immunodeficiency virus (HIV)
infection. Subjects who have evidence of, or test positive for, hepatitis B or
hepatitis C are
excluded as follows:
*A positive test for the hepatitis B virus (HBV) is defined as: 1) positive for
hepatitis B
surface antigen (HBsAg+), or 2) positive for anti-hepatitis B core antibody
(HBcAb+).
*A positive test for the hepatitis C virus (HCV) is defined as: 1) positive for
hepatitis C
antibody (anti-HCV Ab), and 2) positive via a confirmatory test for HCV (for
example,
HCV polymerase chain reaction).
13. Subjects with known TB infection, at high risk of acquiring TB infection,
with latent TB
infection (LTBI), or current or history of NTMB infection (refer to Section
12.7.5 for details
on determining full TB exclusion criteria).
14. Subject has a primary immunosuppressive condition, including taking
immunosuppressive
therapy following an organ transplant or has had a splenectomy.
15. Subjects with concurrent malignancy or a history of malignancy (including
surgically
resected uterine/cervical carcinoma-in-situ) during the past 5 years will be
excluded with the
following exceptions that may be included:
a. *3 excised or ablated basal cell carcinomas of the skin
b. One squamous cell carcinoma of the skin (stage T1 maximum) successfully
excised or
ablated only (other treatments, ie, chemotherapy, do not apply) with no signs of
recurrence or metastases for more than 2 years prior to Screening
c. Actinic keratosis(-es)
d. Squamous cell carcinoma-in-situ of the skin successfully excised or ablated
more than
6 months prior to Screening
16. Subject has a history of a lymphoproliferative disorder including lymphoma
or current signs
and symptoms suggestive of lymphoproliferative disease.
17. Subject has a history of demyelinating disease (including myelitis) or
neurologic symptoms
suggestive of demyelinating disease.
18. Subject has a current or recent history, as determined by the Investigator,
of severe,
progressive, and/or uncontrolled renal, hepatic hematological, endocrine,
pulmonary, cardiac
(eg, congestive heart failure New York Heart Association [NYHA] Grade 3 and 4),
gastrointestinal (GI) (note: subjects with active peptic ulcer disease are
excluded; subjects
with a history of peptic ulcer disease are allowed), or neurological disease.
19. Subjects has a history of uncompensated heart failure, fluid overload, or
myocardial
infarction, or evidence of new-onset ischemic heart disease or in the opinion
of the
Investigator other serious cardiac disease, within 12 weeks prior to Baseline.
20. Subjects with presence of significant uncontrolled neuropsychiatric
disorder, active suicidal
ideation, or positive suicide behavior using the *Baseline* version of the
Columbia-Suicide
Severity Rating Scale (C-SSRS) and the Hospital Anxiety and Depression Scale
(HADS)
with either of the following criteria:
*Subject has a lifetime history of suicide attempt (including an actual
attempt, interrupted
attempt, or aborted attempt), or has suicidal ideation in the past 6 months as
indicated by
a positive response (*Yes*) to either question 4 or question 5 of the
*Screening/Baseline*
version of the C-SSRS at screening.
*HADS Depression score *10 or Anxiety score *15.
21. Subject has >2x upper limit of normal (ULN) of any of the following: alanine
aminotransferase (ALT), aspartate aminotransferase (AST), *alkaline phosphatase
(ALP), or
>ULN total bilirubin (*1.5xULN total bilirubin if known Gilbert*s syndrome). If
subject has
elevations only in total bilirubin that are >ULN and <1.5xULN, fractionate
bilirubin to
identify possible undiagnosed Gilbert*s syndrome (ie, direct bilirubin <35%).
*An isolated elevation between 2xULN and <3xULN of ALP is acceptable in the
absence of
an identified exclusionary medical condition.
Tests that result in ALT, AST, or ALP up to 25% above the exclusion limit may
be repeated
once for confirmation during the Screening Period. Upon retesting, subjects
whose ALT,
AST, or ALP remain above the thresholds defined above, should not be randomized.
For randomized subjects with a Baseline result >ULN for ALT, AST, ALP, or total
bilirubin,
a Baseline diagnosis and/or the cause of any clinically meaningful elevation
must be
understood and recorded in the electronic Case Report form (eCRF).
If a subject has >ULN ALT, AST, or ALP that does not meet the exclusion limit at
Screening, repeat the tests, if possible, prior to dosing to ensure there is no
further ongoing
clinically relevant increase. In case of a clinically relevant increase,
inclusion of the subject
must be discussed with the Medical Monitor.
22. Subjects with clinically significant laboratory abnormalities (eg,
creatinine >1.5xULN,
neutropenia <1.5x109 /L, hemoglobin <8.5g/dL, lymphocytes <1.0 x109 /L, white
blood cell
(WBC) count <3.0x109 , platelets <100 x109 /L). Individual screening tests for
which the
results are in error, borderline, or indeterminate for inclusion in the study,
can be repeated
once for confirmation during the Screening Period if they are within 25% of the
exclusion
limit. Upon retesting, subjects whose results remain outside this threshold
should not be
randomized.
23. Subject has an estimated glomerular filtration rate (GFR) as measured by
Chronic Kidney
Disease Epidemiology Collaboration <60mL/min/1.73m2
24. Subject has a 12-lead ECG with changes considered to be clinically
significant upon medical
review (eg, QT corrected for heart rate [QTc] using Fridericia*s correction
[QTcF] >450ms,
bundle branch block, evidence of myocardial ischemia).
25. Subjects has received any live (includes attenuated) vaccination within the
8 weeks prior to
Baseline (12 months prior to Baseline for the TB Bacille Calmette-Guérin [BCG]
vaccine)
(eg, inactivated influenza and pneumococcal vaccines are allowed but nasal
influenza
vaccination is not permitted). Live vaccines are not allowed during the study
or for 20 weeks
after the final dose of IMP.
Live vaccines include, but are not limited to the following:
*Anthrax vaccine
*Intranasal influenza vaccine
*Measles-mumps-rubella (MMR) vaccine
*Polio live oral vaccine (OPV)
*Smallpox vaccine
*Tuberculosis BCG vaccine (within 12 months prior to Baseline)
*Typhoid live oral vaccine
*Varicella vaccine
*Yellow fever vaccine
26. Subject has a history of chronic alcohol or drug abuse within the previous
6 months.
27. Subjects has any other condition which, in the Investigator's judgment,
would make the
subject unsuitable for inclusion in the study.
28. Subject is Investigator site personnel directly affiliated with this study
and/or their immediate
families. Immediate family is defined as a spouse, parent, child, or sibling,
whether
biological or legally adopted.
29. Subject is a UCB employee or is an employee of a third-party organization
involved in the
study.
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 | EUCTR2017-000957-37-NL |
| CCMO | NL63167.029.17 |