The purpose of this study is to find out how safe and effective a new drug called bimekizumab is for long-term use in treating hidradenitis suppurativa. Bimekizumab (hereafter referred to as *the study drug*) has been approved by the health…
ID
Source
Brief title
Condition
- Skin and subcutaneous tissue disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Evaluate the efficacy of bimekizumab in study participants with moderate to
severe HS
- HiSCR50 at Week 16
Secondary outcome
Evaluate the efficacy of bimekizumab on other measures of disease activity in
study participants with moderate to severe HS
• HiSCR75 at Week 16
• Flare (defined as a >=25% increase in AN count with an
absolute increase in AN count of >=2 relative to Baseline) by Week 16
• Absolute change from Baseline in DLQI Total Score at
Week 16
• Absolute change from Baseline in the Worst HS Skin Pain
score at Week 16, as assessed by the *worst pain* item
(11-point numeric rating scale) in the HSSDD
• Pain response (defined as a decrease from Baseline in
HSSDD weekly worst skin pain score at or beyond the threshold for clinically
meaningful change) at Week 16
Evaluate the safety of bimekizumab in study participants with moderate to
severe HS
- Treatment-emergent AEs
- Serious TEAEs
- TEAEs leading to withdrawal from study
Background summary
Hidradenitis suppurativa or acne inversa is a chronic, inflammatory, recurrent,
debilitating skin disease that usually presents after puberty with painful,
deep-seated, inflamed lesions in the apocrine gland-bearing areas of the body,
most commonly the axillaries, inguinal, and anogenital regions (Dessau
definition, First International Conference on HS, 30 Mar to 01 Apr 2006,
Dessau, Germany). The nodules are often inflamed, can progress to abscess
formation, and may rupture to form fistulas and subsequent scarring. Thus, many
patients with HS develop permanent sequelae of past inflammation that are only
remediable through surgical excision of the involved skin areas. Hidradenitis
suppurativa is also associated with several complications (eg, the development
of anal, urethral, and rectal strictures and fistulas), and the excessive
scarring and fibrosis produced by HS lesions can lead to contractures and
limitations in limb mobility (Alikhan, 2009; Danby, 2010).
Hidradenitis suppurativa is estimated to affect about 1% of the adult European
population, with a female to male ratio of approximately 3:1 (Revuz, 2008;
Naldi, 2006). The prevalence of diagnosed HS in the US may be lower (<0.1%),
although further research is needed to determine the prevalence of undiagnosed
HS in the US (McMillan, 2014). Patients diagnosed with HS often experience a
significant reduction in quality of life (QOL), equivalent to severe PSO
(Sartorius, 2009), due to the location of, and discharge from, the lesions that
leads to an often persistent morbidity due to pain and sequelae from
uncontrolled inflammation (von der Werth, 2001; Wolkenstein, 2007). The
reduction in QOL and persistent morbidity result in functional impairment in
patients with HS similar or greater to that of heart disease, diabetes, or
asthma, when measured by the European Quality-of-Life 5 dimensions 3-level
questionnaire (EQ-5D-3L) scale (Riis, 2016).
Bimekizumab is a humanized full-length mAb of IgG1 subclass being developed for
the treatment of patients with inflammatory diseases such as PSO, psoriatic
arthritis, axial spondyloarthritis, and HS. Bimekizumab has high affinity for
human IL-17A and human IL-17F,
and selectively and potently inhibits the activity of both isoforms in vitro.
The key pro-inflammatory cytokine IL-17A has been demonstrated to, and IL-17F
is believed to, play important roles in autoimmune and inflammatory diseases.
Published data and immunohistochemistry studies performed by UCB have shown
that expression of both IL-17A and IL-17F is present in HS lesions, and there
are published reports highlighting the potential for IL-17A and IL-17F to drive
HS disease pathology (UCB Research Report 40001864; Cho, 2012; Schlapbach,
2011). This supports the hypothesis that the IL-17 cytokine family is a
potential therapeutic target in HS. Bimekizumab is hypothesized to demonstrate
a treatment response in HS because it selectively and potently inhibits the
activity of both IL-17A and IL-17F isoforms in vitro.
Study objective
The purpose of this study is to find out how safe and effective a new drug
called bimekizumab is for long-term use in treating hidradenitis suppurativa.
Bimekizumab (hereafter referred to as *the study drug*) has been approved by
the health authorities for treatment of moderate to severe plaque psoriasis in
adults in the European Union and Great Britain. However, it is still
investigational, which means that is it still being tested, and has not yet
been approved for treatment by the health authorities in other countries or
regions or in other indications.
We compare the effects of the study drug with the effects of a placebo. A
placebo is a substance without active substance, a *fake drug*.
Study design
HS0003 is a Phase 3, randomized, double-blind, placebo-controlled, multicenter,
pivotal study evaluating the efficacy and safety of bimekizumab in study
participants with moderate to severe HS. Study participants meeting the
inclusion criteria who do not meet any exclusion criteria will complete a
Screening Period of 14 days to up to 5 weeks; a double-blind, 48-week Treatment
Period comprising a 16-week Initial Treatment Period and 32-week Maintenance
Treatment Period; and a 20-week Safety Follow-up (SFU) Period following the
final injection of investigational medicinal product (IMP) if study
participants do not enter a subsequent extension study (HS0005) or withdraw
prematurely from treatment.
Study participants will be randomized in a 2:2:2:1 ratio (stratified by Hurley
Stage and current antibiotic use) to 1 of 3 dose regimens of bimekizumab or
placebo as shown in the schematic (Figure 1-1). All doses of IMP will be
administered by sc injection. The primary efficacy variable at Week 16 is
HiSCR50. Study visits will occur at Screening; Baseline
(Week 0); Weeks 1, 2, 4, 6, 8, 10, 12, 14, and 16; and every 2 weeks from Week
16 through
Week 48 for assessments of efficacy, safety, and other measures of QOL/health
status/work productivity. An SFU visit will be conducted 20 weeks after the
final dose of IMP for participants who do not enter the extension study, or who
are prematurely withdrawn from the study.
Intervention
Because of differences in the dosing schedules and in order to maintain
blinding, all study participants will receive 2 injections subcutaneous every 2
weeks from Week 0 to Week 46 as depicted in Table 6*2 (protocol).
Bimekizumab will be administrated via a subcutaneous injection.
Eligible study participants will be randomized in a 2:2:2:1 ratio as noted in
the Study Schema
Participants who will only receive Bimekizumab they will receive 320mg every
two weeks. This will be given with two injections of 160 mg.
There are also 3 groups who will receive both Bimekizumab and a Placebo. Please
see Protocol amendment 2 for a schematic table 6-2 (page 35)
Study burden and risks
At the Baseline visit, the subject will be randomly assigned (like drawing
straws) to receive either the study drug or a placebo for the first 16 weeks.
Neither the subject nor the study doctor will know which treatment the subjects
are receiving, this is called *double blind*. The subject will have a 6 in 7
chance of receiving the active study drug and a 1 in 7 chance of receiving
placebo only for the first 16 weeks of treatment. After 16 weeks, all subjects
will receive the active study drug for the remaining 32 weeks of the study.
Each injection will be given under the skin either on the lower stomach area,
upper arm, or the outer side of the upper thighs. The place of injection will
be rotated between visits. The subject will receive two injections of the
assigned study drug every two weeks during the treatment period.
Assessments done as screening may be repeated, additional procedures include:
• Recording height and weight.
• Check if the subjects are still eligible to take part in the study and decide
if the subject may continue in the study.
• Questions about any health problems including tobacco and alcohol use or
other medical conditions that the subject may have had since the last visit.
• Questions about other medications the subjects are taking during the study.
the subject will also be asked if the subject started, stopped, or modified any
medications since your last visit and this will be recorded by the subjects
study doctor.
• The subject will be asked to complete a daily diary, at the end of every day,
from the start of Screening through the Week 16 visit to assess their symptoms
for the past 24-hours.
• The subject will be asked to give their assessment on the status of your
hidradenitis suppurativa and score the severity of their skin pain at up to 5
visits (Baseline, Weeks 4, 16, 32, and 48 visits).
• Additional questionnaires about;
- symptoms of hidradenitis suppurativa the subject have experienced in past 7
days.
- how their disease affects their quality of life.
- how their disease affects their work efficiency.
Extension Study
At the completion of 48 weeks of Treatment Period, if there is any improvement
in their condition as determined by the study doctor, the subject will be given
an option to participate in an extension study.
Safety Follow-Up / Premature End of Treatment Visit
If the subject do not qualify for, or do not want to participate in the
extension study, the subject will return for a Safety Follow-up visit 20 weeks
after their final dose of study drug.
A Premature End of Treatment visit will be performed if the subject leave the
study early before the study completion at Week 48, either because the subject
decided to discontinue by theirself, or because of safety issues regarding
their personal health as determined by their study doctor. Most of the
assessments performed during the Treatment Period visits will be repeated
during this visit.
If the subject stop receiving the study drug, the subject will still be a part
of the study. The subject will be asked to complete the Premature End of
Treatment visit assessments and return to the clinic for an SFU visit at 20
weeks after their final dose of study drug.
Allée de la Recherche 60
Brussel 1070
BE
Allée de la Recherche 60
Brussel 1070
BE
Listed location countries
Age
Inclusion criteria
- Participant must be at least 18 years of age, at the time of signing the
informed consent. If a study participant is under the local age of consent and
is at least 18 years of age, written informed consent will be obtained from
both the study participant and the legal representative
- Study participants must have a diagnosis of Hidradenitis Suppurativa (HS)
based on clinical history and physical examination for at least 6 months prior
to the Baseline visit; diagnosis must be verifiable through medical notes and
documentation.
- Study participant must have HS lesions present in at least 2 distinct
anatomic areas (eg, left and right axilla), 1 of which must be at least Hurley
Stage II or Hurley Stage III at both the Screening and Baseline visits
- Study participant must have moderate to severe HS defined as a total of >=5
inflammatory lesions (ie, number of abscesses plus number of inflammatory
nodules) at both the Screening and Baseline visits
- Study participant must have had a history of inadequate response to a course
of a systemic antibiotics at the Screening Visit for treatment of HS as
assessed by the Investigator through study participant interview and review of
medical history; inadequate response must be verifiable through medical notes
and documentation.
- A female study participant is eligible to participate if she is not pregnant,
not breastfeeding, and at least one of the following conditions applies:
a) Not a woman of childbearing potential (WOCBP)
OR
b) A WOCBP who agrees to follow the contraceptive guidance during the treatment
period and for at least 20 weeks after the last dose of investigational
medicinal product (IMP)
Exclusion criteria
1. Study participant has any medical or psychiatric condition that, in the
opinion of the
Investigator, could jeopardize or would compromise the study participant*s
ability to participate in this study as determined by the Investigator based on
protocol-required assessments.
2. Study participant has a draining tunnel count of >20 at the Baseline Visit.
3. Study participant has any other active skin disease or condition (eg,
bacterial cellulitis,
candida intertrigo, extensive condyloma) that may, in the opinion of the
Investigator, interfere with the assessment of HS.
4. Study participant has a diagnosis of sarcoidosis, systemic lupus
erythematosus, or active
IBD. Note: Study participants with a diagnosis of Crohn*s disease or ulcerative
colitis are allowed if they have no active symptomatic disease at Screening or
Baseline.
5. Study participant has a primary immunosuppressive condition, including taking
immunosuppressive therapy following an organ transplant, or has had a
splenectomy.
6. Female study participant who is breastfeeding, pregnant, or plans to become
pregnant during
the study or within 20 weeks following the final dose of IMP.
7. Study participant has an active infection or history of infection(s) as
follows:
* Any infection requiring systemic treatment within 14 days prior to Baseline
* A serious infection, defined as requiring hospitalization or intravenous
anti-infective(s)
within 2 months prior to the Baseline Visit
A history of opportunistic, recurrent, or chronic infections that, in the
opinion of the
Investigator, might cause this study to be detrimental to the study
participant. Opportunistic infections are infections caused by uncommon
pathogens (eg, Pneumocystis jirovicii, cryptococcosis), or unusually severe
infections caused by common pathogens (eg, cytomegalovirus, herpes zoster)
8. Study participant has any of the following:
* Known active TB disease
* History of active TB involving any organ system unless adequately treated
according to
World Health Organization/Centers for Disease Control and Prevention
therapeutic guidance and proven to be fully recovered upon consult with a TB
specialist
* Latent TB infection (LTBI). Participants with LTBI diagnosed during Screening
must
have completed a course of prophylaxis prior to IMP dosing. Participants can be
rescreened after completion of a full course of prophylaxis plus a wash-out of
least
5 half-lives of the prophylactic medication(s) prior to Baseline to avoid any
interference
with the study efficacy measurements (eg, concomitant antibiotics). Prophylaxis
should be in accordance with applicable clinical guidelines and TB specialist
judgment based on the origin of infection.
* High risk of exposure to TB infection
* Current pulmonary nontuberculous mycobacterial (NTM) infection or history of
pulmonary NTM infection unless proven to be fully recovered
Note: For further information relating to definitions of known active TB, past
history of TB, LTBI, high risk of acquiring TB infection and NTM infection
refer to Section 8.2.6.
9. Study participant has an acute or chronic hepatitis B virus, hepatitis C
virus (HCV), or
human immunodeficiency virus (HIV) infection. Study participants who have
evidence of, or tested positive for, hepatitis B or hepatitis C will be
excluded. A positive test for hepatitis B virus is defined as: 1) positive for
hepatitis B surface antigen, or 2) positive for anti-hepatitis B core antibody.
A positive test for HCV is defined as: 1) positive for hepatitis C antibody,
and 2) positive via a confirmatory test for HCV (for example, HCV polymerase
chain reaction).
10. Study participants with concurrent malignancy are excluded. Study
participants with a
history of malignancy within the past 5 years prior to the Screening Visit are
excluded, EXCEPT if the malignancy was a cutaneous squamous or basal cell
carcinoma, or in situ cervical cancer that has been treated and is considered
cured.
11. Study participant has a history of a lymphoproliferative disorder including
lymphoma or
current signs and symptoms suggestive of lymphoproliferative disease.
12. Study participant has had major surgery within the 3 months prior to the
Baseline Visit, or
has planned major surgery after entering the study.
13. Study participant has any systemic disease (ie, cardiovascular,
neurological, renal, liver,
metabolic, gastrointestinal, hematological, immunological, etc.) considered by
the degree during the course of the study.
14. Study participant has had a myocardial infarction or stroke within the 6
months prior to the
Screening Visit.
15. Study participant has a history of chronic alcohol or drug abuse within 6
months prior to
Screening as evaluated by the Investigator based on medical history, interview,
and/or results of the Screening urine drug screen.
16. Study participant has the presence of active suicidal ideation, or positive
suicide behavior using the "Screening" version of the electronic Columbia
Suicide Severity Rating Scale (eC-SSRS) with either of the following criteria:
* Study participant has a history of a suicide attempt within the 5 years prior
to the
Screening Visit. Study participants with a history of a suicide attempt more
than 5 years ago should be evaluated by a mental healthcare practitioner before
enrolling into the study.
* Suicidal ideation in the past month prior to the Screening Visit as indicated
by a positive
response (*Yes*) to either Question 4 or Question 5 of the *Screening* version
of the
eC-SSRS.
17. Study participant has presence of moderately severe major depression or
severe major
depression indicated by a score of >=15 using the screening Patient Health
Questionnaire Depression Module (PHQ-9). Medication used to treat depression
should be stable for
8 weeks prior to Baseline.
18. Study participant has a known hypersensitivity to any components of
bimekizumab or
comparative drugs as stated in this protocol.
19. Study participant has had prior treatment with an IL-17 biologic response
modifier or
has participated in IL-17 biologic response modifier study unless an
appropriate washout has been performed since the last dose of IMP (within 6
moths prior to the Baseline Visit or 5 hal-lives [whichever is greater]).
20. Study participant received prescription topical therapies for the treatment
of HS within
14 days prior to the Baseline Visit.
21. Study participant is currently receiving systemic nonbiologic or biologic
therapies for HS
with potential therapeutic impact for HS. Note: If study participant received
systemic nonbiologic or biologic therapies for HS and stopped these treatments,
washout periods should be applied as shown in Table 6*3. Note: this does not
apply to study participants who may be eligible for randomization into the
antibiotic strata.
22. If study participant is using concomitant, non-opioid analgesics for
HS-related or
non-HS-related pain as permitted by protocol, they should be on a stable
(scheduled) dose for at least 14 days prior to the Baseline Visit and
anticipate continuing that dose through
Week 16 unless a decrease in dose is warranted based on symptoms. Opioid
analgesics are
excluded. Note: As needed (PRN) use is not considered a stable dose, but (for
example) taking a nonsteroidal anti-inflammatory drug (NSAID) 3 times per week,
every week is considered a stable dose.
23. Study participant has received any live (including attenuated) vaccination
within the 8 weeks
prior to the Baseline Visit (eg, inactivated influenza and pneumococcal
vaccines are allowed, but nasal influenza vaccination is not permitted). Live
vaccines are not allowed during the study, including the SFU Period (20 weeks
after the final dose of IMP).
24. Study participant has received Bacillus Calmette-Guerin vaccination within
1 year prior to
IMP administration.
Prior/Concurrent clinical study experience
25. Study participant has previously participated in this study or study
participant has previously
been assigned to treatment in a study of the medication under investigation in
this study, and received at least 1 dose of IMP (including placebo).
26. Study participant is currently participating in another study of a systemic
medication under
investigation, including SFU. Study participant must be washed out of the
medication as indicated in Table 6*3.
27. Study participant is currently participating in another study of a topical
medication under
investigation, including SFU. Study participant must be washed out of the
medication for 4 weeks prior to the Baseline Visit.
28. Study participant is currently, or was within the 4 weeks prior to the
Baseline Visit,
participating in another study of a medical device under investigation.
Diagnostic assessments
29. Study participant has laboratory abnormalities at Screening, including any
of the following:
* >=3× the upper limit of normal (ULN) of any of the following: alanine
aminotransferase
(ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP)
* Bilirubin >1.5×ULN (isolated bilirubin >1.5×ULN is acceptable if bilirubin is
fractionated and direct bilirubin <35%)
* White blood cell count <3.00×103/µL
* Absolute neutrophil count <1.5×103/µL
* Lymphocyte count <500 cells/µL
* Hemoglobin <8.5g/dL
Note: 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. Upon retesting, study
participants whose results remain outside this threshold should not be
randomized.
30. Study participant has any other laboratory abnormality, which, in the
opinion of the
Investigator, will prevent the study participant from completing the study or
will interfere with the interpretation of the study results.
Other exclusions
31. Study participant is a UCB employee or is an employee of third-party
organizations involved
in the study.
32. Study participant and/or his or her immediate family member is an employee,
volunteer, or
other worker at the investigative site either affiliated or not affiliated with
this study. Immediate family is defined as a spouse, parent, child, or sibling
whether biological or legally adopted.
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 | EUCTR2019-002550-23-NL |
| ClinicalTrials.gov | NCT04242446 |
| CCMO | NL72332.078.20 |