Primary objective:-To assess whether ixekizumab is superior to adalimumab at Week 24 in the treatment of patients with active PsA as measured by American Collegeof Rheumatology 50 (ACR50) and Psoriasis Area and Severity Index 100 (PASI 100)Major…
ID
Source
Brief title
Condition
- Joint disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
-Proportion of patients simultaneously achieving ACR50 and PASI 100 at Week 24
Secondary outcome
-Proportion of patients achieving ACR50 in each treatment group at Week 24
-Proportion of patients achieving PASI 100 in each treatment group at Week 24
PsA Endpoints
Time course of response to treatment over 52 weeks as measured by:
-Proportion of patients achieving ACR20, ACR50, and ACR70 responses
-Change from baseline in individual components of the American College of
Rheumatology (ACR) Core Set - tender joint count, swollen joint count,
patient*s pain assessment, Patient*s Global Assessment of Disease Activity,
Physician*s Global Assessment of Disease Activity, C-reactive protein (CRP),
and Health Assessment Questionnaire*Disability Index (HAQ-DI) score
-Proportion of patients simultaneously achieving ACR50 and PASI 100 response
-Change from baseline in the Disease Activity Score (28 diarthrodial joint
count) based on C-reactive protein (DAS28-CRP)
-Proportion of patients achieving Minimal Disease Activity (MDA)
-Proportion of patients achieving Psoriatic Arthritis Response Criteria (PsARC)
-Change from baseline in Modified Composite Psoriatic Disease Activity Index
(CPDAI) score
-Proportion of patients achieving low disease activity or remission according
to the Modified Composite Psoriatic Disease Activity Index definition
-Proportion of patients with HAQ-DI improvement *0.35
-Change from baseline in the Spondyloarthritis Research Consortium of Canada
(SPARCC) Enthesitis Index score in patients with enthesitis at
baseline (ie, baseline SPARCC Enthesitis Index score >0)
-Change from baseline in the Leeds Enthesitis Index (LEI) score in patients
with enthesitis at baseline (ie, baseline LEI score >0)
-Proportion of patients with resolution in enthesitis in the subgroup of
patients with enthesitis at baseline as measured by the SPARCC
Enthesitis Index (ie, baseline SPARCC Enthesitis Index score >0)
-Proportion of patients with resolution in enthesitis in the subgroup of
patients with enthesitis at baseline as measured by the LEI (ie, baseline
LEI score >0)
-Change from baseline in the Leeds Dactylitis Index-Basic (LDI-B) score in
patients with dactylitis at baseline (ie, baseline LDI-B score >0)
-Proportion of patients with resolution in dactylitis in the subgroup of
patients with dactylitis at baseline as measured by the LDI-B (ie, baseline
LDI-B score >0)
Psoriasis/Nail Endpoints
Time course of response to treatment over 52 weeks as measured by:
-Change from baseline in body surface area (BSA)
-Proportion of patients who achieve the following PASI scores: PASI 75, PASI
90, or PASI 100 (defined as 75%, 90%, and 100% improvement from baseline in
PASI criteria, respectively)
-Proportion of patients achieving an absolute PASI score <1 or <2 or <3
-Change from baseline in the Nail Psoriasis Severity Index (NAPSI) Fingernails
score in the subgroup of patients with fingernail involvement at baseline (ie,
baseline NAPSI Fingernails score >0)
QoL Endpoints
Time course of response to treatment over 52 weeks as measured by:
-Change from baseline in the Itch Numeric Rating Scale (NRS) score
-Proportion of patients with Itch NRS score equal to 0
-Change from baseline in Fatigue Severity NRS score
-Change from baseline in Medical Outcomes Study 36-Item Short Form Health
Survey (SF-36)
o Physical Component Summary score
o Mental Component Summary score
-Change from baseline in measures of health utility (European Quality of Life*5
Dimensions 5 Level health outcomes instrument [EQ-5D-5L])
-Change from baseline in Dermatology Life Quality Index (DLQI) total score
-Change from baseline in Treatment Satisfaction Questionnaire Safety
-Change from baseline in Columbia*Suicide Severity Rating Scale (C-SSRS)
Background summary
During the last decade, the treatment of psoriatic arthritis (PsA) has
significantly changed. Methotrexate (MTX) or other conventional synthetic
disease-modifying anti-rheumatic drugs (csDMARD) such as sulfasalazine or
leflunomide are usually initiated as a first line of treatment.
In patients with active PsA and an inadequate response or intolerance to a
csDMARD, the use of a biologic DMARD (bDMARD) is recommended according to the
European League Against Rheumatism (EULAR) and Group for Research and
Assessment of Psoriasis and Psoriatic
Arthritis (GRAPPA) working group.
Based on current treatment recommendations, a tumor necrosis factor (TNF)
inhibitor is the usual first option for a bDMARD, mainly because of the
long-term experience and the well-established efficacy and safety profile of
these agents. Five TNF inhibitors have been approved and are available in major
markets for the treatment of PsA to-date: etanercept, infliximab, adalimumab,
golimumab, and certolizumab. In addition, biosimilars of infliximab,
etanercept, and adalimumab have been recently approved for use in PsA. New
bDMARDs targeting different mechanisms of action have also been approved for
the treatment of PsA, with ustekinumab targeting the IL-12/IL-23 pathway,
secukinumab and brodalumab targeting the IL-17 pathway, and apremilast, an oral
molecule, inhibiting phosphodiesterase 4 (PDE 4). As additional therapies
become available, an important question is whether bDMARDs with different
mechanisms of action have comparable clinical efficacy and safety. Ixekizumab
has been studied in patients with active PsA in a study that included
adalimumab as an active control reference arm. Yet to date, no results of a
direct comparator study in patients with PsA comparing 2 bDMARDs have been
published. This type of study design is important for informing evidence-based
treatment decisions with regard to a TNF inhibitor.
In this study, adalimumab has been chosen as the active comparator, as it is
recognized as a standard of care for a bDMARD in the treatment of active PsA.
Study objective
Primary objective:
-To assess whether ixekizumab is superior to adalimumab at Week 24 in the
treatment of patients with active PsA as measured by American College
of Rheumatology 50 (ACR50) and Psoriasis Area and Severity Index 100 (PASI 100)
Major Secondary Objectives:
-To assess whether ixekizumab is noninferior to adalimumab at Week 24 in the
treatment of patients with active PsA as measured by ACR50
-To assess whether ixekizumab is superior to adalimumab at Week 24 in the
treatment of patients with active PsA as measured by PASI 100
Other Secondary Objectives:
-To assess the effect of treatment with ixekizumab compared with adalimumab as
measured by efficacy and quality of life outcomes
Study design
Study RHCF is a Phase 3b/4, multicenter, randomized, open-label, parallel-group
study with blinded outcomes assessments evaluating the efficacy and safety of
ixekizumab versus adalimumab in patients with PsA who are bDMARD naive during a
52-week treatment period.
The study will consist of 3 periods:
- Period 1: Screening Period (Visit 1) up to 28 days before randomization
(Visit 2)
- Period 2: Open-Label Treatment Period (Visit 2 through Visit 11) from Week 0
to Week 52
- Period 3: Post-Treatment Follow-Up Period occurring from last treatment visit
during Period 2 or Early Termination Visit (ETV) up to a minimum of 12 weeks
after that visit
Intervention
At Week 0 (randomization, Visit 2), routine safety assessments, laboratory
tests, and clinical efficacy assessments (including height, weight, and
temperature, as well as review of habits) will be performed on eligible
patients according to the Schedule of Activities (Protocol section 2). Patients
will be randomized at a 1:1 ratio to either ixekizumab 80 mg or adalimumab 40
mg.
The study will consist of 3 periods:
- Period 1: Screening Period (Visit 1) up to 28 days before randomization
(Visit 2)
- Period 2: Open-Label Treatment Period (Visit 2 through Visit 11) from Week 0
to Week 52
- Period 3: Post-Treatment Follow-Up Period occurring from last treatment visit
during Period 2 or Early Termination Visit (ETV) up to a minimum of 12 weeks
after that visit
All patients randomized to ixekizumab will receive a starting dose of 160 mg at
randomization (Visit 2 [Week 0]). Patients with moderate-to-severe plaque Ps
will receive ixekizumab 80 mg Q2W from Week 2 to Week 12 and Q4W thereafter.
Patients not meeting criteria for moderate-to-severe plaque Ps at randomization
will receive ixekizumab 80 mg Q4W starting at Week 4.
Patients randomized to adalimumab with moderate-to-severe plaque Ps will
receive a starting dose of 80 mg at randomization (Visit 2 [Week 0]) followed
by 40 mg Q2W starting at Week 1.
Patients not meeting criteria for moderate-to-severe plaque Ps will receive a
starting dose of 40 mg at randomization (Visit 2) followed by 40 mg Q2W
starting at Week 2 (see Protocol section 7.1 for details regarding treatments
administered).
Study burden and risks
The Investigational Product and other medication required by Protocol and the
study procedures are associated with certain risks and discomforts, as
described in the patient information leaflet. The combination of experimental
medicine and study procedures may be associated with additional risks or
discomforts that at this point are not fully known. The most common side
effects associated with lxekizumab are: Runny nose and sore throat; cold
symptoms; Upper respiratory tract infection; injection site reaction; Headache;
Worsening of rheumatoid arthritis; Urinary tract Infection; Sinus irritation;
Injection site pain; Injection site redness; Diarrhea; Back pain; Bronchitis;
High blood pressure; Dizziness; Joint pain; Cough; Nausea; Vertigo.
The subjects undergo an number of study procedures such as SC injections, TB
test and X-ray. These procedures may also be accompanied by certain risks. The
procedures may also have other unknown risks. These risks are described in the
Informed consent form. Selectively targeting IL-17A with ixekizumab is
hypothesized to provide therapeutic benefit without unduly impacting host
defenses. As such, ixekizumab may offer a therapeutic option for patients who
have failed NSAIDs and for patients who have lost response, failed to respond,
or are intolerant to current marketed drugs. Ixekizumab may offer a more
favorable safety profile compared to currently marketed therapies.
Papendorpseweg 83
Utrecht 3528 BJ
NL
Papendorpseweg 83
Utrecht 3528 BJ
NL
Listed location countries
Age
Inclusion criteria
-Presents with established diagnosis of active psoriatic arthritis for at least 6 months, and currently meets Classification for Psoriatic Arthritis (CASPAR) criteria
-Active psoriatic arthritis (PsA) defined as the presence of at least 3 tender and at least 3 swollen joints
-Presence of active plaque psoriasis
-Men must agree to use a reliable method of birth control or remain abstinent during the study
-Women must agree to use reliable birth control or remain abstinent during the study and for at least 12 weeks after stopping treatment
Exclusion criteria
-Current or prior use of biologic agents for treatment of Ps or PsA
-Evidence of active inflammatory arthritic syndromes or spondyloarthropathies other than PsA
-Have participated in any study with interleukin 17 (IL-17) antagonists, including ixekizumab
-Serious disorder or illness other than psoriatic arthritis
-Serious infection within the last 3 months
-Women who are breastfeeding
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 | EUCTR2016-004585-25-NL |
| CCMO | NL61357.048.17 |