Period 1: The first objective, of period 1, is to compare the safety and efficacy of ABT-494 30 mg (QD) and 15 mg QD versus placebo on a background of csDMARD(s) for the treatment of signs and symptoms of rheumatoid arthritis (RA) in bDMARD-…
ID
Source
Brief title
Condition
- Autoimmune disorders
- Joint disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the proportion of subjects achieving ACR20 response
(US/FDA regulatory purposes) or the proportion of subjects achieving LDA
(EU/EMA regulatory purposes) at Week 12.
Secondary outcome
Secondary endpoints at week 12 are:
1. Change from baseline in DAS28 (CRP);
2. ACR20 response rate;
3. ACR50 response rate;
4. Change from baseline in HAQ-DI;
5. ACR70 response rate;
6. Change from baseline in SF-36 PCS;
7. ACR20 response rate at week 1.
Additional endpoints at all visits are:
* Change from baseline in individual components of ACR response;
* ACR20/50/70 response rates;
* Change from baseline in DAS28 (CRP) and DAS28 (erythrocyte
sedimentation rate [ESR]);
* Change from baseline in morning stiffness (severity and duration);
* Proportion of subjects achieving LDA and proportion of subjects achieving CR
based on DAS28 (CRP), DAS28 (ESR), Simplified Disease Activity Index
(SDAI), and CDAI criteria.
Additional endpoints (at Weeks 4, 12, and 24) are:
* Change from baseline in EQ-5D-5L;
* Change from baseline in ISI (sleep);
* Change from baseline in SF-36.
Assessments to evaluate efficacy of treatment in Period 2 will be analyzed for
above-mentioned measures at
Weeks 36, 48 and every 12 weeks thereafter until completion of the study.
Background summary
Rheumatoid arthritis (RA) is a chronic, systemic, autoimmune disease
characterized by inflammation of the articular synovial membrane. The hallmark
feature of patients affected by RA is an inflammatory process manifested by
persistent symmetric polyarthritis of synovial joints. Early therapy with
disease-modifying antirheumatic drugs (DMARDs) is the standard of care,
although a significant proportion of patients either do not achieve disease
remission or become refractory to available therapies as the disease
progresses. Novel therapies are therefore required to complement the available
interventions to address the unmet need in the treatment of patients with RA.
Evidence suggests that inhibition of Janus kinase (JAK)-mediated pathways is a
promising approach for the treatment of patients with this chronic disease.
AbbVie is developing a small molecule inhibitor of JAK, ABT-494, that may
address the current medical needs.
Study objective
Period 1:
The first objective, of period 1, is to compare the safety and efficacy of
ABT-494 30 mg (QD) and 15 mg QD versus placebo on a background of csDMARD(s)
for the treatment of signs and symptoms of rheumatoid arthritis (RA) in
bDMARD-inadequate response (bDMARD-IR) or bDMARD-intolerant subjects with
moderately to severely active RA.
Periode 2:
The objective of this study in periode 2, is to evaluate the long-term safety,
tolerability, and efficacy of ABT-494 30 mg QD and 15 mg QD in subjects with RA
who have completed Period 1.
Study design
This is a phase 3, multicenter study that includes to periods. Period 1 is a
randomized, double-blind, placebo-controlled treatment period of 24 weeks.
Period 2 is a blinded long-term extension period for subjects who completed
period 1.
Subjects will be randomized in a 2:2:1:1 ratio to one of 4 treatment groups:
- Group 1: ABT-494 30 mg QD (week 1 to 12) --> ABT-494 30 mg QD (week 12 and
thereafter)
- Group 2: ABT-494 15 mg QD (week 1 to 12) --> ABT-494 15 mg QD (week 12 and
thereafter)
- Group 3: Placebo (week 1 to 12) --> ABT-494 30 mg QD (week 12 and thereafter)
- Group 4: Placebo (week 1 to 12) --> ABT-494 15 mg QD (week 12 and thereafter)
The study will be conducted in approximately 300 research centers and
approximately 250 subjects will be enrolled.
Intervention
Subjects who are randomized in the ABT-494 treatment groups will start their
dose ABT-494 30 mg QD or ABT-494 15 mg QD orally at Baseline and must take
their oral dose of medication once daily for 12 weeks. Subjects who are
randomized in the Placebo treatment groups will receive matching placebo for
ABT-494 to remain the blind and must take their oral dose of medication oral
once daily for 12 weeks. From week 12 and thereafter, subjects who are assigned
to the Placebo group will be switched to receive ABT-494 30 mg QD or ABT-494 15
mg QD.
Subjects who complete the week 24 visit (end of period 1) will enter the
blinded long term extension portion of the study (period 2). Subjects who are
assigned to ABT-494 treatment groups in period 1 will continue to receive
ABT-494 15 mg QD or 30 mg QD per original randomization assignment in a blinded
manner. Subjects who are assigned to placebo for the first 12 weeks of period
1 and subsequently switched to receive ABT-494 15 mg or 30 mg QD per
pre-specified randomization assignments at week 12, will continue to receive
the same dose of ABT-494 per original randomization assignment in a blinded
manner.
Subjects who do not achieve CDAI * 10 at Week 24 should have background
medication(s) adjusted or initiated after assessments for Week 24 have been
completed.
Study burden and risks
Subjects participating in this study are required to come to all scheduled
visits and complete the procedures, as described in section E.4. Risks of
participating in this study are: - higher dose and/or frequency of drug
administration - extra time - (extra) procedures) - come to all scheduled
visits -adverse events (described in section E.9) - discomfort of tests that
will be conducted during study.
Wegalaan 9
Hoofddorp 2132 JD
NL
Wegalaan 9
Hoofddorp 2132 JD
NL
Listed location countries
Age
Inclusion criteria
* Adult male or female, at least 18 years old.;* Diagnosis of RA for * 3 months.;* Subjects have been treated for * 3 months with * 1 bDMARD therapy, but continue to exhibit active RA or had to discontinue due to intolerability or toxicity, irrespective of treatment duration prior to the first dose of study drug. ;* Subjects have been receiving csDMARD therapy * 3 months and on a stable dose for * 4 weeks prior to the first dose of study drug. The following csDMARDs are allowed: MTX, sulfasalazine, hydroxychloroquine, chloroquine, and leflunomide. A combination of up to two background csDMARDs is allowed except the combination of MTX and leflunomide.;* Meets the following criteria: * 6 swollen joints (based on 66 joint counts) and * 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits.
Exclusion criteria
* Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to tofacitinib, baricitinib, and filgotinib).;* History of inflammatory joint disease other than RA. History of secondary Sjogren's Syndrome is permitted.
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 | EUCTR2015-003335-35-NL |
| ClinicalTrials.gov | NCT02706847 |
| CCMO | NL54437.091.16 |