Main objectives:1. To evaluate the efficacy of upadacitinib compared with placebo on reduction of signs and symptoms as measured by proportion of subjects who achieve an Assessment of SpondyloArthritis international Society (ASAS) 40 response at…
ID
Source
Brief title
Condition
- Joint disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Proportion of participants with Assessment of SpondyloArthritis international
Society (ASAS) 40 response
(It is defined as a >= 40% improvement and an absolute improvement of >= 2
units (on a scale of 0 to 10) from Baseline in at least three of the following
four domains, with no worsening at all in the remaining domain:
a. Patient's Global Assessment
b. Pain
c. Function
d. Inflammation)
Secondary outcome
1. Change from Baseline in Ankylosing Spondylitis Disease Activity Score
(ASDAS);
2. Change from Baseline in MRI Spondyloarthritis Research Consortium of Canada
(SPARCC) score (Spine);
3. Proportion of subjects with BASDAI 50 response;
4. Change from Baseline in Ankylosing Spondylitis Quality of Life (AS QoL);
5. Proportion of subjects with ASAS partial remission (PR);
6. Change from Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI);
7. Change from Baseline in Linear Bath Ankylosing Spondylitis Metrology Index
(BASMIlin);
8. Change from Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score
(MASES);
9. Change from Baseline in Work Productivity and Activity Impairment (WPAI);
10. Change from Baseline in ASAS Health Index (HI);
11. ASAS 20;
12. Change from Baseline in MRI Spondyloarthritis Research Consortium of Canada
(SPARCC) score Sacroiliac (SI) joints.
Background summary
Ankylosing spondylitis (AS) is a type of arthritis in which there is chronic
inflammation of the joints of the spine. Despite recent advances in the
treatment, there remains a significant unmet medical need as only approximately
45% to 50% of patients show an ASAS 40 response and only approximately 15% to
20% achieve a state of remission. In addition, treatment options are still
limited when compared with other rheumatic diseases such as rheumatoid
arthritis (RA) or Psoriatic Arthritis (PsA).
Inhibition of JAK-mediated pathways is a promising approach for the treatment
of patients with chronic inflammatory diseases such as AS. AbbVie is developing
a small molecule inhibitor of JAK, upadacitinib, that may address the current
needs.
Study objective
Main objectives:
1. To evaluate the efficacy of upadacitinib compared with placebo on reduction
of signs and symptoms as measured by proportion of subjects who achieve an
Assessment of SpondyloArthritis international Society (ASAS) 40 response at
Week 14 in subjects with active ankylosing spondylitis (AS) who have had an
inadequate response to at least two nonsteroidal anti-inflammatory drugs
(NSAIDs) or intolerance to or a contraindication for NSAIDs, and who are
biologic disease-modifying antirheumatic drug (bDMARD)-naïve.
2. To assess the safety and tolerability of upadacitinib in subjects with
active AS who have had an inadequate response to at least two NSAIDs or
intolerance to or a contraindication for NSAIDs, and who are bDMARD-naïve.
Secondary objective:
To evaluate the safety, tolerability, and efficacy of upadacitinib through up
to 2 years of treatment in subjects who have completed Period 1.
Study design
This is a Phase 2/3 multicenter study that includes two periods. Period 1 is a
14-week randomized, double-blind, parallel-group, placebo-controlled period
designed to compare the safety and efficacy of upadacitinib dose A versus
placebo. Period 2 is an open-label long-term extension to evaluate the
long-term safety, tolerability, and efficacy of upadacitinib Dose A QD in
subjects who have completed Period 1.
Intervention
Period 1: subjects will take one tablet of upadacitinib (Dose A) or placebo
once daily for 14 weeks.
Period 2: subjects will take one tablet of upadacitinib (Dose A) once daily for
194 weeks.
Study burden and risks
There will be 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. Women of Childbearing Potential
should practice a method of birth control, during the study through at least 30
days after the last dose of study drug. If male, subjects must practice
contraception during the study through at least 30 days after last dose of
study drug. Additionally, male subjects must agree not to donate sperm from
Study Day 1 through 30 days after the last dose of study drug.
Subjects will either receive upadacitinib or placebo during the study. The most
common side effects reported during previous studies of upadacitinib were
headache, upper chest infection, common cold, diarrhea and cough. An elevation
of an enzyme in the blood called creatine phosphokinase (CPK, a protein
released mainly from muscle cells) was observed in treated patients. Safety
monitoring will be done during the study.
The hypothesis that upadacitinib should be effective in targeting inflammation
associated with AS and the lack of effectiveness of other treatments indicate
that there is an acceptable rationale to conduct this study. There may or may
not be benefit for study subjects but there may be benefit for future patients
with ankylosing spondylitis. The subject*s condition may get better, may
worsen, or may stay unchanged.
Wegalaan 9
Hoofddorp 2132JD
NL
Wegalaan 9
Hoofddorp 2132JD
NL
Listed location countries
Age
Inclusion criteria
1. Male or female >= 18 years of age., 2. Subject with a clinical diagnosis of
AS and meeting the modified New York Criteria for AS., 3. Subject must have
baseline disease activity as defined by having a Bath Ankylosing Spondylitis
Disease Activity Index (BASDAI) score >= 4 and a Patient's Assessment of Total
Back Pain score >= 4 based on a 0 - 10 Numeric Rating Scale (NRS) at the
Screening and Baseline Visits., 4. Subject has had an inadequate response to at
least two NSAIDs over an at least 4-week period in total at maximum recommended
or tolerated doses, or subject has an intolerance to or contraindication for
NSAIDs as defined by the Investigator., 5. If entering the study on concomitant
MTX, leflunomide, SSZ and/or hydroxychloroquine, subject must be on a stable
dose of MTX (<= 25 mg/week) and/or SSZ (<= 3 g/day) and/or hydroxychloroquine (<=
400 mg/day) or leflunomide (<= 20 mg/day) for at least 28 days prior to the
Baseline Visit. A combination of up to two background csDMARDs is allowed
EXCEPT the combination of MTX and leflunomide., 6. If entering the study on
concomitant oral corticosteroids, subject must be on a stable dose of
prednisone (<= 10 mg/day), or oral corticosteroid equivalents, for at least 14
days prior to the Baseline Visit. Subject must be on stable dose(s) for at
least 14 days prior to the Baseline Visit.
Exclusion criteria
1. Prior exposure to any Janus kinase (JAK) inhibitor (including but not
limited to tofacitinib, baricitinib, and filgotinib)., 2. Prior exposure to any
biologic therapy with a potential therapeutic impact on spondyloarthritis
(SpA)., 3. Intra-articular joint injections, spinal/paraspinal injection(s),
or parenteral administration of corticosteroids within 28 days prior to the
Baseline Visit. Inhaled or topical corticosteroids are allowed., 4. Subject on
any other DMARDs (other than those allowed), thalidomide, or apremilast within
28 days or five half-lives (whichever is longer) of the drug prior to the
Baseline Visit., 5. Subject on opioid analgesics (except for combination
acetaminophen/codeine or acetaminophen/hydrocodone which are allowed) or use of
inhaled marijuana within 14 days prior to the Baseline Visit., 6. Subject has
a history of inflammatory arthritis of different etiology other than axial SpA
(including but not limited to rheumatoid arthritis (RA), psoriatic arthritis
(PsA), mixed connective tissue disease, systemic lupus erythematosus, reactive
arthritis, scleroderma, polymyositis, dermatomyositis, fibromyalgia), or any
arthritis with onset prior to 17 years of age., 7. Laboratory values meeting
the following criteria within the Screening period prior to the first dose of
study drug: serum aspartate transaminase (AST) > 2 × ULN; serum alanine
transaminase (ALT) > 2 × ULN; estimated glomerular filtration rate (GFR) by
simplified 4-variable Modification of Diet in Renal Disease (MDRD) formula < 40
mL/min/1.73m2; hemoglobin < 10 g/dL, total white blood cell count (WBC) <
2,500/µL; absolute neutrophil count (ANC) < 1,500/µL; absolute lymphocyte count
< 800/µL; and platelet count < 100,000/µL.
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 | EUCTR2017-000431-14-NL |
| CCMO | NL62813.042.17 |
| Other | nog niet bekend |