Primary ObjectivesThe primary objective of this study is to evaluate the efficacy and safety of guselkumab in pediatric participants aged >=6 through =6 through =6 through
ID
Source
Brief title
Condition
- Autoimmune disorders
- Epidermal and dermal conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Efficacy evaluations include:
• Investigator*s Global Assessment (IGA)
• Psoriasis Area and Severity Index (PASI)
• Body Surface Area (BSA)
• Children*s Dermatology Life Quality Index (CDLQI)
• Family Dermatology Life Quality Index (FDLQI)
Secondary outcome
The co-primary and major secondary endpoints for Part 1, with the primary
comparisons between the guselkumab and placebo groups, include:
Co-primary Endpoints
• The proportion of participants achieving an IGA score of cleared (0) or
minimal (1) at Week 16.
• The proportion of participants with a PASI 75 response at Week 16.
Major Secondary Endpoints
• The proportion of participants achieving a PASI 90 response at Week 16.
• The proportion of participants achieving an IGA score of cleared (0) at Week
16.
• The proportion of participants achieving a PASI 100 response at Week 16.
• The change from baseline in CDLQI at Week 16.
Other Secondary Endpoints
Secondary endpoints for Part 1 of the study include:
• The proportion of retreated participants that achieve a PASI 90 response over
time after retreatment.
• The proportion of retreated participants that achieve PASI responses (PASI
50, 75, 90, and 100) or IGA responses (IGA of cleared [0], minimal [1], or mild
[2], IGA of cleared [0] or minimal [1], and IGA of cleared [0]) over time after
retreatment.
• The time to loss of 50% of the Week 16 PASI improvement (ie, time to
retreatment) after withdrawal.
• The time to loss of PASI 90 response after withdrawal.
• The proportion of participants achieving a PASI 50 response at Week 16.
• The proportion of participants who achieve an IGA score of mild or better
(<=2) at Week 16.
• The percent improvement from baseline in PASI over time through Week 16.
• The proportion of PASI responses (PASI 50, 75, 90, and 100) over time through
Week 16.
• The proportion of IGA responses (IGA of cleared [0], minimal [1], or mild
[2], IGA of cleared [0] or minimal [1], and IGA of cleared [0]) over time
through Week 16.
• The proportion of participants with CDLQI=0 or 1 at Week 16 among randomized
participants with a baseline CDLQI>1
• Body surface area involved (BSA) and change from baseline in BSA at Week 16
will be compared between the guselkumab group and the placebo group.
• BSA and change from baseline in BSA will be summarized over time through Week
16.
• The proportion of participants with FDLQI=0 or 1 at Week 16 among randomized
participants with a baseline FDLQI>1.
• The change from baseline in FDLQI at Week 16.
For Part 2 of the main study, PASI responses, IGA responses, PASI percent
improvement, change from baseline in CDLQI and FDLQI, the proportion of
participants achieving a CDLQI of 0 or 1, and the proportion of participants
achieving a FDLQI of 0 or 1 will be summarized over time through Week 52.
Background summary
Plaque psoriasis is a chronic, immunologically-mediated, inflammatory skin
disease of unknown etiology affecting 2% to 4% of the general population. The
pathogenesis of plaque psoriasis involves environmental factors and immune
dysregulation in genetically-predisposed individuals. Substantial evidence
indicates that IL-23 plays an important role in innate and adaptive immune
responses, and may play a pivotal role in the pathogenesis of psoriasis
vulgaris.
Adult and pediatric plaque psoriasis share similar clinical manifestations,
histological features, genetic factors, and treatment options.6 Taken together,
the data demonstrate that a complex network of immune mediators (cells and
cytokines) drive the inflammatory skin processes of plaque psoriasis in adults
and children.
Plaque psoriasis is characterized by symmetrically distributed, well-defined,
sharply demarcated, indurated, erythematous plaques that are covered by
friable, dry, white-silvery scale and is reported to account for up to 84% of
psoriasis in pediatric patients. Areas of the body that are frequently involved
include the scalp, elbows, knees, buttocks, and genitalia. Definitions of
plaque psoriasis severity differ depending on the source, but are generally
related to the extent of the body surface involved, although the extent of
exposed skin involved is also often considered.
Studies addressing the age of onset of psoriasis have suggested that 2
subgroups exist: early onset disease (before 30 years of age, including
pediatric onset) and late onset disease (after age 30). Generally, the clinical
manifestations of plaque psoriasis in patients with pediatric onset and those
with adult or late onset disease are similar, and not clinically
distinguishable. Therefore, the consensus of the literature is essentially that
plaque psoriasis is a life-long chronic disease with a variable age of onset,
and that pediatric plaque psoriasis is probably most accurately characterized
as early onset disease rather than as an entity distinct from adult plaque
psoriasis.
The traditional paradigm for the treatment of plaque psoriasis follows a
stepwise approach to treatment starting with topical agents, followed by
phototherapy, and then systemic agents. Recently, several biologic psoriasis
treatments have been approved for use in patients with pediatric plaque
psoriasis. Currently, etanercept (ENBREL®), adalimumab (HUMIRA®) and
ustekinumab (STELARA®) are approved for various pediatric age groups in some
jurisdictions. Among these biologics, etanercept is currently approved in a
broad pediatric age range and the largest number of geographic regions.
Although stepwise therapy is mentioned frequently in the literature, the
optimal treatment approach for pediatric patients with chronic plaque psoriasis
is far less clear than for adults due to the practical scheduling issues of
phototherapy in school aged children, the known, often cumulative, toxicities
of traditional systemic therapies and the paucity of rigorous clinical data or
approved therapeutic options for this age group. For these reasons, a
proportion of pediatricpatients with plaque psoriasis are currently
undertreated, and could benefit from additional safe, effective, and convenient
therapies. Based on currently available data, guselkumab could offer efficacy,
safety and convenience advantages compared with available therapies.
Study objective
Primary Objectives
The primary objective of this study is to evaluate the efficacy and safety of
guselkumab in pediatric participants aged >=6 through <18 years with chronic
plaque psoriasis.
Secondary Objectives
The secondary objectives of this study are:
• To evaluate the pharmacokinetics (PK) and immunogenicity of guselkumab in
pediatric participants aged >=6 through <18 years with chronic plaque psoriasis.
• To evaluate the effect of guselkumab on the dermatologic health-related
quality of life in pediatric participants aged >=6 through <18 years with
chronic plaque psoriasis.
• To evaluate maintenance of response in participants who have active treatment
withdrawn.
• To evaluate the efficacy and safety of retreatment with guselkumab.
• To generate clinical usability data and use experience with the VarioJect
presentation (PFS-V) in pediatric participants with chronic plaque psoriasis
and a body weight <70 kg.
Study design
This is a Phase 3, multicenter, randomized, placebo- and active
comparator-controlled study evaluating the efficacy, safety, and PK of
subcutaneously (SC) administered guselkumab for the treatment of chronic plaque
psoriasis in pediatric participants >=6 to <18 years of age that cannot be
adequately controlled with phototherapy and/or topical agents.
The main study will be conducted in 2 parts. In Part 1, the efficacy, safety,
and PK of a weight-based dose regimen of guselkumab will be evaluated in
pediatric participants during a 16-week randomized, placebo- and active
comparator-controlled period followed by an uncontrolled period of withdrawal
and retreatment or initiation of treatment with guselkumab through Week 52.
Etanercept (active comparator) will be administered in an open-label fashion
during the controlled period of the study and efficacy will be assessed by a
blinded efficacy evaluator. Part 1 of the study will be divided into Part 1a
(>=12 to <18 years of age [ie, adolescents]) and Part 1b (>=6 to <12 years of
age). Enrollment of participants >=6 to <12 years of age in Part 1b will
commence only after all participants >=12 to <18 years of age in Part 1a have
completed Week 16, all available safety data have been reviewed by an
independent Data Monitoring Committee (DMC), with no important safety concerns
identified, and all available guselkumab PK data for the >=12 to <18-year-old
participants through Week 16 have been evaluated via PK modeling and simulation
to confirm that the body weight-based dose used in Part 1a provided systemic
exposure comparable to adults.
Part 2 of the study will be an open-label, single-arm study to collect
additional efficacy, safety, and PK data for pediatric participants with a
weight-based dose regimen of guselkumab through Week 52. Part 2 will begin
after the reviews of safety and PK data through Week 16 for all participants
>=12 to <18 years of age in Part 1a have been completed, and will enroll enough
additional participants to achieve a total of at least 100 participants exposed
to guselkumab in this study. Enrollment of participants >=6 to <12 years of age
in Part 2 will commence only after all participants in Part 1b have completed
16 weeks of treatment, all available safety data have been reviewed by an
independent DMC, and all PK data through Week 16 from Part 1b have been
evaluated via PK modeling and simulation to confirm that the body weight-based
dose used in Part 1b provided systemic exposure comparable to adults. Clinical
usability data of the to-be-marketed VarioJect presentation (PFS-V) will be
collected in Part 2 of the study.
A long-term extension (LTE) of the study will be initiated at Week 52.
There are 3 database locks (DBL) planned for this study at Week 16, Week 52
(end of the main study), and at the end of the study (end of the LTE). The Week
16 database lock will occur after all participants in Part 1 of the study
complete their Week 16 visit and will include only data from Part 1 of the
study. The sponsor will be unblinded after the Week 16 database lock for Part 1
has occurred. The Week 52 database lock will occur after all participants in
both Part 1 and Part 2 of the study complete their Week 52 visit. Additional
database locks may be performed if deemed necessary.
Intervention
Guselkumab and placebo for guselkumab will be provided in a single-use
prefilled syringe (PFS) assembled with the UltraSafe Plus* Passive Needle Guard
(PFS-U) or a VarioJect variable dose injector (PFS-V). Commercially available
etanercept will be provided in a prefilled syringe or as a powder and solvent
for solution for injection.
Participants randomized to guselkumab will receive a dose based on body weight.
Participants will receive 1 of the following dose levels depending on their
weight:
• Weight <70 kg: 1.3 mg/kg administered using the PFS-V
• Weight >=70 kg: 100 mg administered using the PFS-U
Participants randomized to placebo will receive injections with a volume
determined using the same weight based dose calculation for guselkumab.
Commercially available etanercept will be supplied and participants will
receive a dose based on body weight:
• <63 kg: 0.8 mg/kg once weekly using a powder and solvent for solution for
injection.
• >=63 kg: 50 mg once weekly administered using a prefilled syringe.
Dose Regimen:
Participants in Part 1 will be randomized to 1 of 3 treatment groups to receive:
• Group I: Weight-based guselkumab dose up to 100 mg SC at Weeks 0, 4, and 12.
• Group II: Weight-based placebo for guselkumab dose administered SC at Weeks
0, 4, and 12.
• Group III: Weight-based etanercept dose up to 50 mg SC weekly through Week 15.
From Week 16 through Week 52:
• Group Ia: Participants randomized to guselkumab who are PASI 90 responders at
Week 16 will not receive any additional doses of guselkumab until they lose
>=50% of their Week 16 PASI response, at which time they will receive a
weight-based guselkumab SC dose, followed by a dose 4 weeks later, and every 8
weeks (q8w) thereafter through Week 52.
• Group Ib: Participants randomized to guselkumab who are PASI 90 nonresponders
at Week 16 will receive a placebo injection at Week 16 and continue treatment
with guselkumab q8w from Week 20 through Week 52.
• Group IIa: Participants randomized to placebo who are PASI 90 responders at
Week 16 will not receive any additional doses of study intervention until they
lose >=50% of their Week 16 PASI response, at which time they will receive a
weight-based guselkumab SC dose, followed by a dose 4 weeks later, and q8w
thereafter through Week 52.
• Group IIb: Participants randomized to placebo who are PASI 90 nonresponders
at Week 16 will receive a weight-based guselkumab dose at Weeks 16 and 20,
followed by q8w dosing thereafter through Week 52.
• Group III: Participants randomized to etanercept who elect to continue in the
study will receive a weight-based guselkumab dose at Weeks 20 and 24, followed
by q8w dosing thereafter through Week 48.
Participants enrolled in Part 2 of the study will receive a weight-based dose
of open-label guselkumab SC at Weeks 0, 4 and q8w thereafter through Week 52.
Participants who complete Week 52 of the main study and who have had a
beneficial response from guselkumab treatment as determined by the
investigator, will have the option of continuing with a weight-based guselkumab
q8w regimen until one of the following occurs: 1) they have reached 18 years of
age and reside in a country where guselkumab is approved for treatment of
plaque psoriasis in adults and have had the opportunity to complete up to 1
year in the LTE, 2) marketing authorization is obtained for guselkumab for
treatment of plaque psoriasis for patients >=6 to <18 years of age, 3) marketing
authorization is denied for guselkumab for the treatment of plaque psoriasis in
pediatric patients, or 4) the company decides to no longer pursue an indication
in plaque psoriasis in the pediatric population.
Study burden and risks
The patient visits the investigator in the part 1 of the study every 4 weeks;
in part 2 every 4 or 8 weeks; during the long term extension every 8 weeks.
There are multiple blood samples planned. In part 1 and part 2 there are 11
venepunctures. In the long term extension trial there are venipunctures every
24 weeks. A physical examination is performed several times. Questionnaires are
taken during all visits.
Side effects of the treatment may occur. These are described in the information
for the patient.
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Listed location countries
Age
Inclusion criteria
1. Participant must be a boy or girl >=6 to <18 years of age.
2. Have a diagnosis of chronic plaque-type psoriasis for at least 6 months ,
prior to first administration of study intervention, defined as having at
screening and baseline:
• Investigator*s Global Assessment (IGA) >=3 and
• Psoriasis Area and Severity Index (PASI) >=12 and
• >=10% Body Surface Area (BSA) involvement and
at least one of the following:
- very thick lesions or
- clinically relevant facial, genital, or hand/ foot involvement or
- PASI >=20 or
- >20% BSA involvement or
- IGA=4
3. Be a candidate for phototherapy or systemic treatment of plaque psoriasis
4. Have plaque psoriasis considered by the investigator as inadequately
controlled with phototherapy and/or topical therapy after an adequate dose and
duration of therapy.
5. Be considered, in the opinion of the investigator, a suitable candidate for
etanercept (ENBREL) therapy according to their country's approved ENBREL
product labeling.
6. Be otherwise healthy on the basis of physical examination, medical history,
and vital signs performed at screening. Any abnormalities, must be consistent
with the underlying illness in the study population and this determination must
be recorded in the participant's source documents and initialed by the
investigator.
7. Contraceptive use by boys or girls should be consistent with local
regulations regarding the use of contraceptive methods for those participating
in clinical studies.
Before randomization, a girl must be either:
a. Not of childbearing potential defined as:
- premenarchal. A premenarchal state is one in which menarche has not yet
occurred.
- permanently sterile Permanent sterilization methods include hysterectomy,
bilateral salpingectomy, bilateral tubal occlusion/ligation procedures, and
bilateral oophorectomy.
- or otherwise be incapable of pregnancy.
b. Of childbearing potential and practicing a highly effective method of
contraception and agrees to remain on a highly effective method while receiving
study intervention and until 12 weeks after last dose - the end of relevant
systemic exposure.
8. A girl must agree not to donate eggs for the purposes of assisted
reproduction during the study and for a period of at least 12 weeks following
the last dose of study intervention.
9. A girl of childbearing potential must have a negative urine pregnancy test
at screening and at all visits when study intervention is to be administered.
10. A boy who is sexually active with a female of childbearing potential and
who has not had a vasectomy must agree to use a barrier method of birth control
or a partner with an occlusive cap, during the study and for at least 12 weeks
after receiving the last administration of study intervention. All boys must
also agree to not donate sperm during the study and for at least 12 weeks after
receiving the last administration of study intervention.
11. Are considered eligible according to the following TB screening criteria:
• Have no history of latent or active TB before screening.
• Have no signs or symptoms suggestive of active TB upon medical history and/or
physical examination.
• Have had no recent close contact with a person with active TB.
Exclusion criteria
Medical history-related exclusion criteria:
1. Currently has nonplaque forms of psoriasis
2. Has current drug-induced psoriasis
3. Is pregnant, nursing, or planning a pregnancy or fathering a child while
enrolled in the study or within 12 weeks after receiving the last
administration of study intervention.
4. Has a history of or current signs or symptoms of severe, progressive, or
uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine,
pulmonary, cardiac, neurologic, cerebral, or psychiatric disease.
5. Has a transplanted organ
6. Has had major surgery within 8 weeks before screening, or will not have
fully recovered from such surgery, or has such surgery planned during the time
the participant is expected to participate in the study.
7. Has unstable suicidal ideation or suicidal behavior:
• Participants >=12 to <18 years of age may not be randomized if they have:
- a Columbia-Suicide Severity Rating Scale rating at screening of: suicidal
ideation with intention to act suicidal ideation with specific plan and intent
or non-suicidal self-injurious behavior within the past 6 months, OR
- a C-SSRS rating at screening of suicidal behavior
• Participants >=6 to <12 years of age may not be randomized if they have:
- a C-SSRS rating at screening of: suicidal ideation with intention to act
suicidal ideation with specific plan and intent r suicidal behavior or any
self-injurious behavior ever
• Participants with a C-SSRS rating at screening of Wish to be Dead (*Ideation
level 1*), Non-Specific Active Suicidal Thoughts or Active Suicidal Ideation
with Any Methods (Not Plan) without Intent to Act may not be randomized if:
- participants >=12 to <18 years of age have one of the above C-SSRS ratings
within the past 6 months and are determined to be at risk by the investigator
after being discussed with the medical monitor or designee.
- participants >=6 to <12 years of age have one of the above C-SSRS ratings
ever (lifetime) and are determined to be at risk by the investigator after
being discussed with the medical monitor or designee.
8. Is known to have had a substance abuse problem within the previous 12
months.Medical therapies-related exclusion criteria:
9. Has previously received guselkumab or etanercept.
10. Has any contraindications to the use of etanercept per local prescribing
information.
11. Criterion modified per Amendment 4:
11.1 Are considered eligible according to the following TB screening criteria:
- have no history of latent or active TB before screening
- have no signs or symptoms suggestive of active TB upon medical history and/or
physical examination.
- have had no recent close contact with a person with active TB
- within 10 weeks before the first administration of study intervention, have a
negative QuantiFERON-TB Gold test result. Within 10 weeks before the first
administration of the study intervention, a negative tuberculin skin test is
additionally required if the QuantiFERON-TB gold test is not
approved/registered in that country or the tuberculin skin test is mandated by
local health authorities.
12. Is not a suitable candidate for anti-TNFα therapy for the following reasons:
• Has a history of known demyelinating diseases such as multiple sclerosis or
optic neuritis.
• Has known or suspected intolerance or hypersensitivity to anti-TNFα
medications (eg, clinical lupus-like syndrome, serum sickness-like reaction).
• Has a history of, or concurrent congestive heart failure (CHF), including
medically controlled CHF.
13. Has received any therapeutic agent directly targeted to IL-12/23, IL-17, or
IL-23 within 6 months of the first administration of study intervention
(including but not limited to ustekinumab, tildrakizumab, secukinumab,
ixekizumab, risankizumab, or brodalumab).
14. Has received natalizumab, efalizumab, or agents that deplete B or T cells
within 12 months of screening, or, if after receiving these agents, evidence is
available at screening of persistent depletion of the targeted lymphocyte
population.Please refer to pages 38-42 of the protocol for the complete
overview of the exclusion criteriahat coun
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 | EUCTR2017-003053-42-NL |
| ClinicalTrials.gov | NCT03451851 |
| CCMO | NL65294.091.18 |