Period 1: The first objective, of period 1, is to compare the safety and efficacy of ABT-494 15 mg QD monotherapy, and 30 mg QD monotherapy versus weekly methotrexate (MTX) monotherapy for the treatment of signs and symptoms of rheumatoid arthritis…
ID
Source
Brief title
Condition
- Autoimmune disorders
- Joint disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint in Period 1 is the proportion of subjects achieving ACR50
response (US/FDA regulatory purposes) or the proportion of subjects achieving
Clinical Remission (CR) (EU/EMA regulatory purposes) at Week 24. For Japan/PMDA
regulatory purposes, the primary endpoints are the proportion of subjects
achieving ACR20 response and change from baseline in modified Total Sharp Score
(mTSS) at Week 24.
Secondary outcome
Ranked secondary endpoints are:
1. Change from baseline in DAS28 (CRP);
2. Change from baseline in HAQ-DI;
3. ACR20 response rate;
4. ACR50 response rate;
5. Change from baseline in modified Total Sharp Score (mTSS);
6. ACR70 response rate;
7. Proportion of subjects achieving LDA based on DAS28 (CRP) * 3.2;
8. Change from baseline in SF-36 PCS;
9. Proportion of subjects with no radiographic progression (defined as change
from baseline in mTSS * 0) at Weeks 24 and 48.
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]);
* Proportion of subjects achieving LDA or CR by DAS28(CRP), DAS28(ESR),
Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index
(CDAI);
* Change from baseline in morning stiffness (severity and duration);
Additional endpoints (at Weeks 12, 24, and 48) are:
* Change from baseline in EQ-5D-5L;
* Change from baseline in FACIT-F;
* Change from baseline in WPAI;
* Change from baseline in SF-36.
Additional endpoints (at Weeks 24 and 48) are:
* Change from baseline in mTSS;
* Proportion of subjects with no radiographic progression (defined as change
from baseline in mTSS * 0);
* Change from baseline in radiographic joint space narrowing and erosion scores.
Assessments to evaluate efficacy of treatment in Period 2 will be analyzed for
above-mentioned measures at
Weeks 60, 72, 84, 96 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 15 mg QD monotherapy, and 30 mg QD monotherapy versus weekly
methotrexate (MTX) monotherapy for the treatment of signs and symptoms of
rheumatoid arthritis (RA) in MTX-naïve subjects with moderately to severely
active RA. The second objective is to compare the efficacy of ABT-494 15 mg QD
monotherapy and ABT-494 30 mg QD monotherapy versus weekly MTX monotherapy for
prevention of structural progression.
Period 2:
The objective of this study, of period 1, is to evaluate the long-term safety,
tolerability, and efficacy of ABT-494 in subjects with RA
who have completed Period 1.
Study design
This is a Phase 3 multicenter study that includes two periods. Period 1 is a
48-week randomized, double-blind, parallel-group, placebo-controlled and active
comparator-controlled period. Period 2 is a long-term for subjects who have
completed Period 1 and is blinded until the last subject completes the last
visit of Period 1.
Subjects will be randomized in a 2:2:1 ratio to one of 3 treatment groups:
- Group 1: ABT-494 15 mg QD
- Group 2: ABT-494 30 mg QD
- Group 3: MTX once a week
The study will be conducted in approximately 300 research centers and
approximately 975 subjects will be enrolled.
Intervention
Subjects who are assigned to ABT-494 15 mg will start oral at 15 mg/day at
Baseline. Subjects who are assigned to ABT-494 30 mg will start oral at 30
mg/day at Baseline. Subjects who are assigned to the MTX treatment group will
start oral MTX treatment at 10 mg/week.
To maintain the blind, subjects will be provided with matching placebo. In
addition, all subjects should take a dietary supplement of oral folic acid (or
equivalent) throughout study participation.
1) Subjects who are originally randomized to MTX:
- those who achieve clinical remission by CDAI (clinical disease activity index
< 2.8) at week 26 will continue blinded treatment with MTX.
- those who do not achieve clinical remission by CDAI but achieve * 20%
improvement in both TJC and SJC compared to baseline will continue on blinded
TMX and the investigator should initiate or increase background RA medication.
- those who do not achieve clinical remission by CDAI and do not achieve * 20%
improvement in both TJC and SJC compared to baseline will be re-randomized in a
1:1 ratio to receive blinded ABT-494.
2: Subjects who were originally randomized to ABT-494:
- those who achieve clinical remission by CDAI (clinical disease activity index
< 2.8) at week 26 will continue blinded treatment with ABT-494.
- those who do not achieve clinical remission by CDAI but achieve * 20%
improvement in both TJC and SJC compared to baseline continue on blinded
ABT-494 and the investigator should initiate or increase background RA
medications.
- those who do not achieve clinical remission by CDAI and do not achieve * 20%
improvement in both TJC and SJC compared to baseline will add MTX to ABT-494 in
a blinded matter.
Subjects who complete the Week 48 visit (end of period 1) will enter the
long-term extension of the study (period 2). Subjects will continue the same
treatment per assignment at the end of period 1 in a blinded fashion. When the
last subject completes the last visit of period 1 (week 48), study drug
assignment may be unblinded and subjects would then be dispensed study drug in
an open-label fashion until completion of period 2.
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
1. Adult male or female, at least 18 years old.;2. Diagnosis of RA for * 3 months.;3. Naïve to MTX or, if already on MTX, have received no more than 3 weekly MTX doses with requirement to complete a 4-week MTX washout before the first dose of study drug.;4. Subjects with prior exposure to csDMARDs other than MTX may be enrolled if completed the
washout period as specified below or should be at least five times the mean terminal elimination
half-life of a drug:
*** 4 weeks prior to first dose of study drug for minocycline, penicillamine, sulfasalazine,
hydroxychloroquine, chloroquine, azathioprine, gold formulations, cyclophosphamide,
tacrolimus, cyclosporine, mycophenolate;
*** 8 weeks prior to first dose of study drug for leflunomide if no elimination procedure was
followed, or adhere to an elimination procedure.;5. Subject meets both of the following disease activity criteria:
a. * 6 swollen joints (based on 66 joint counts) and * 6 tender joints (based on 68 joint counts) at
Screening and Baseline Visits; and
b. hsCRP * 5 mg/L (central lab, ULN 2.87 mg/L) at Screening Visit.
Exclusion criteria
1. Intolerant to MTX.;2. Prior exposure to any JAK inhibitor (including but not limited to tofacitinib, baricitinib, and filgotinib).;3. Prior exposure to any bDMARD(s).;4. 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 | EUCTR2015-003334-27-NL |
| ClinicalTrials.gov | NCT02706873 |
| CCMO | NL54442.091.15 |