This is a Phase 3 multicenter study that includes two periods. Period 1 is designed to compare the safety, tolerability, and efficacy of upadacitinib low dose once daily (QD) and high dose B QD versus placebo and versus adalimumab every other week (…
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The proportion of subjects achieving ACR20 response.
Secondary outcome
1. Change from baseline in HAQ-DI
2. Proportion of subjects achieving a static Investigator Global Assessment
(sIGA) of Psoriasis of 0 or 1 and at least a 2-point improvement from baseline
3. Psoriasis Area Severity Index (PASI) 75 response (for subjects with >= 3% BSA
psoriasis at baseline)
4. Change from baseline in modified PsA Sharp/van der Heijde Score (SHS)
5. Proportion of subjects achieving Minimal Disease Activity (MDA)
6. Change from baseline in Leeds Enthesitis Index (LEI)
7. Change from baseline in Leeds Dactylitis Index (LDI)
8. ACR 20 response rate (non-inferiority of upadacitinib vs adalimumab);
9. Change from baseline in SF-36 PCS
10. ACR 20 response rate (superiority of upadacitinib vs adalimumab);
11. Change from baseline in Patient's Assessment of Pain NRS (superiority of
upadacitinib vs. adalimumab);
12. Change from baseline in HAQ-DI (superiority of upadacitinib vs. adalimumab);
13. Change from baseline in FACIT-Fatigue Questionnaire;
14.Change from baseline in Self-Assessment of Psoriasis Symptoms (SAPS)
Questionnaire
15. ACR 50/70 response rate
16. ACR 20 response rate at Week 1
Background summary
Psoriatic Arthritis (PsA) is a chronic systemic inflammatory disease classified
as a subtype of spondyloarthritis (SpA) and characterized by the association of
arthritis and psoriasis.
Patients with PsA experience varying combinations of disease manifestations
affecting the synovium, tendons, entheses, skin, and bone.
PsA patients require treatment of the entire spectrum of disease manifestations.
Despite the beneficial results achieved with currently available biologic
agents, there remains a clear medical need for additional therapeutic options
in PsA for patients with inadequate response to or intolerance to currently
available therapies.
Study objective
This is a Phase 3 multicenter study that includes two periods. Period 1 is
designed to compare the safety, tolerability, and efficacy of upadacitinib low
dose once daily (QD) and high dose B QD versus placebo and versus adalimumab
every other week (eow) in participants with moderately to severely active
Psoriatic Arthritis (PsA) and have an inadequate response to non-biologic
DMARDs (DMARD-IR). Period 1 is also designed to compare the efficacy of
upadacitinib low dose QD and high dose QD versus placebo for the prevention of
structural progression. Period 2 evaluates the safety, tolerability and
efficacy of upadacitinib low dose QD and high dose QD in participants with PsA
who have completed Period 1.
Study design
A Phase 3, Randomized, Double-Blind, Study Comparing upadacitinib to Placebo
and to Adalimumab in Subjects with Active Psoriatic Arthritis Who Have a
History of Inadequate Response to at Least One Non-Biologic Disease Modifying
Anti-Rheumatic Drug (DMARD).
Intervention
Each study participant will need to take study drug by mouth once daily
(upadacitinib low dose or high dose, or matching placebo tablets) and
injections under the skin every 2 weeks (adalimumab or matching placebo
injections.
Study burden and risks
There is a higher burden for subjects participating in this trial compared to
their standard of care. Subject will be
visiting the hospital more frequently. During these visits study procedures
will be performed including blood sampling and questionnaires. Subject will
also be tested for TB, significant heart conditions, pregnancy, HCV/HBV and HIV.
Subjects will also complete a daily diary and questionnaire. Women of
childbearing potential should practice a method of birth control, during the
study through at least 30 days after the last dose of oral study drug and 150
days after the last dose of injectable drug.
Subjects will either receive upadacitinib, adalimumab or placebo during the
study. The most common side effects reported during previous studies of
upadacitinib were headache, upper chest infection, common cold, back pain,
diarrhea and cough. An elevation of a protein in the blood called creatine
phosphokinase (CPK, a protein released mainly from muscle cells) was observed
in treated patients.
Common side effects seen in subjects on adalimumab are nasopharyngitis (sore
throat), upper respiratory tract infection, headache, nausea, diarrhea,
bronchitis, cough, sinusitis, hypertension (increase in blood pressure),
influenza (flu), urinary tract infection, back pain, and rash.
Safety monitoring will be done during the study.
Despite the availability of various PsA therapies, many patients still do not
respond adequately to these treatments, or gradually lose response over time.
There is evidence for clinical benefit of JAK inhibition in PsA based on 2
Phase 3 studies of a non-selective JAK inhibitor. The risks and burden
associated with participating in this study are acceptable in regards to the
potential benefit study subjects could possibly have.
Knollstrasse 50
Ludwigshafen 67061
DE
Knollstrasse 50
Ludwigshafen 67061
DE
Listed location countries
Age
Inclusion criteria
1. Male or female, at least 18 years of age
2. Diagnosed with psoriatic arthritis with symptom onset at least 6 months
prior to the Screening Visit and fulfillment of the Classification Criteria for
PsA (CASPAR)
3. Subject has active disease at Baseline defined as >= 3 tender joints (based
on 68 joint counts) and >= 3 swollen joints (based on 66 joint counts) at
Screening and Baseline Visits
4. Diagnosis of active plaque psoriasis or documented history of plaque
psoriasis
5. Subject is on current treatment with <= 2 nonbiologic DMARDs
6. Subject has had an inadequate response to previous or current treatment with
at least 1 non-biologic DMARD (MTX, SSZ, LEF, apremilast, bucillamine, or
iguratimod), or subject has an intolerance to or contraindication for DMARDs
7. Presence of either at Screening:
• >= 1 erosion on x-ray
• hs-CRP > laboratory-defined upper limit of normal (ULN)
Exclusion criteria
1. Prior exposure to any Janus Kinase (JAK) inhibitor
2. Current treatment with > 2 non-biologic DMARDs; or use of DMARDs other than
MTX, SSZ, LEF, apremilast, HCQ, bucillamine, or iguratimod; or use of MTX in
combination with LEF.
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 | EUCTR2016-004130-24-NL |
| ClinicalTrials.gov | NCT03104400 |
| CCMO | NL60267.078.17 |