The primary objective of the study is to determine whether baricitinib is superior to placebo in the treatment of patients with moderately to severely active rheumatoid arthritis (RA) despite methotrexate treatment (ie, inadequate response to…
ID
Source
Brief title
Condition
- Autoimmune disorders
- Joint disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective of the study is to determine whether baricitinib is
superior to placebo in the treatment of patients with moderately to severely
active RA despite MTX treatment (ie, MTX IR), as assessed by the proportion of
patients achieving ACR20 at Week 12.
Secondary outcome
The major secondary objectives of the study are to evaluate the efficacy of
baricitinib versus placebo or adalimumab as assessed by:
• change from baseline to Week 24 in structural joint damage as measured by
modified Total Sharp Score (mTSS [van der Heijde method]) compared to placebo
• change from baseline to Week 12 in Health Assessment Questionnaire-Disability
Index (HAQ-DI) score compared to placebo
• change from baseline to Week 12 in DAS28-high-sensitivity C-reactive protein
(hsCRP) compared to placebo
Please refer to section 6.2 (Secondary Objectives) page 29 of the protocol for
the complete list.
Background summary
Management of RA has improved substantially in recent years. In addition to
reduction of signs and symptoms, improvement of physical function, and
inhibition of structural damage, better patient outcomes and clinical remission
are now considered achievable goals. Therefore, the current recommended primary
target for treatment of RA should be a state of clinical remission (Smolen et
al. 2010; Felson et al. 2011).
Despite a variety of approved agents for RA, complete or sustained disease
remission is unusual. Conventional disease-modifying anti-rheumatic drugs
(cDMARDs) have been used with some success.
In addition to cDMARDs, biological agents that block or antagonize critical
inflammatory mediators, T cells, or B cells can reduce pain and swelling and
provide joint protection against structural damage. The efficacy of these
biologics, particularly in combination with MTX, has been shown to have a
clinically important effect on the signs and symptoms of RA (Fleischmann 2005).
However, disease progression can still occur even for patients who achieve
apparent adequate control of their signs and symptoms with cDMARDs and/or
biologic therapies (Klareskog et al. 2009; Rubbert-Roth and Finckh 2009).
Accordingly, a significant unmet need remains for more effective and better
tolerated treatments for RA.
Baricitinib (LY3009104) is an oral Janus kinase 1 (JAK1)/Janus kinase 2 (JAK2)
selective inhibitor representing a potentially effective therapy for treatment
of patients with moderately to severely active rheumatoid arthritis (RA). The
rationale for the current study is to confirm the efficacy and to continue to
define the safety profile of 4 mg baricitinib when administered once daily (QD)
to patients with RA who have had an inadequate response to methotrexate (MTX)
therapy. The safety and tolerability data from this study are intended to
inform the current understanding of the benefit-risk relationship for
baricitinib in patients with RA.
Study objective
The primary objective of the study is to determine whether baricitinib is
superior to placebo in the treatment of patients with moderately to severely
active rheumatoid arthritis (RA) despite methotrexate treatment (ie, inadequate
response to methotrexate [MTX-IR]), as assessed by the proportion of patients
achieving a 20% improvement in American College of Rheumatology criteria
(ACR20) at Week 12.
Study design
Study I4V-MC-JADV (JADV) will be a 52-week, Phase 3, multicenter, randomized,
double-blind, double-dummy, placebo- and active-controlled, parallel-group,
outpatient study comparing the efficacy of baricitinib versus placebo on signs
and symptoms, function, remission, and structural progression in patients with
moderately to severely active RA who have had an insufficient response to
methotrexate (MTX) and who have never been treated with a biologic
disease-modifying antirheumatic drug (DMARD) (ie, MTX-IR patients).
The study will include a noninferiority comparison of baricitinib versus
adalimumab on signs and symptoms.
A total of 1280 patients are planned for enrollment in this study (480 to
receive baricitinib, 480 to receive placebo, and 320 to receive adalimumab).
After the Week 52 study visit, eligible patients may proceed to a separate
extension study (Study I4V-MC-JADY) lasting for up to 2 years or to the
posttreatment follow-up period of this study (Part C).
Study JADV will consist of 4 parts:
• Screening: Screening period lasting from 3 to 42 days prior to Visit 2 (Week
0)
• Part A: double-blind, placebo- and active-controlled period from Week 0
through Week 24
• Part B: double-blind, active-controlled period from Week 24 through Week 52
• Part C: posttreatment follow-up period
Planned Duration of Treatment: 52 weeks.
Screening period: 3 to 42 days
Treatment period: 52 weeks
Follow-up period: 28 days
Intervention
Baricitinib will be administered as a 4-mg tablet once daily (QD). The dose
for patients with renal impairment, defined as estimated glomerular filtration
rate (eGFR) <60 mL/min/1.73 m2, will be 2 mg baricitinib QD.
Patients not assigned to the baricitinib treatment arm will receive either a
4-mg or 2-mg matching placebo tablet. Adalimumab (40 mg) will be administered
by subcutaneous (SC) injection biweekly (ie, every 2 weeks). Patients not
assigned to adalimumab will receive a matching placebo SC injection biweekly.
Patients will continue to take their background MTX therapy during the course
of the study.
Study burden and risks
There may be risks or side effects either related to the drugs or the study
procedures.
As of 28 March 2012, 766 adults (188 healthy volunteers, 475 patients with
rheumatoid arthritis (RA), 67 subjects with psoriasis (Ps), and 36 people with
damaged kidneys) from 18 to 80 years of age, plus 2 children with rare
diseases, have taken baricitinib.
Baricitinib is a molecule that blocks the effects of proteins in the body
called Janus kinases. Blocking these proteins can affect the immune system.
One effect may be a reduction in inflammatory and autoimmune diseases such as
rheumatoid arthritis (RA), psoriasis (Ps), or diabetic nephropathy. Other drugs
that affect the immune system can increase the risk of infection and cancer.
Baricitinib may also increase these risks.
A complete overview of the risks and discomforts related to the study drugs and
the study procedures can be found in the patient information brochure.
Erl Wood Manor Sunninghill Road
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Erl Wood Manor Sunninghill Road
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GB
Listed location countries
Age
Inclusion criteria
1. are at least 18 years of age
2. have a diagnosis of adult-onset RA as defined by the ACR/EULAR 2010 Criteria for the Classification of RA (Aletaha et al. 2010)
3. have moderately to severely active RA defined as the presence of at least 6/68 tender joints and at least 6/66 swollen joints
a. If surgical treatment of a joint has been performed, that joint cannot be counted in the TJC and SJC for entry or enrollment purposes.
4. have a C-reactive protein (CRP) (or hsCRP) measurement >=6 mg/L based on the most recent data (if available)
5. have had regular use of MTX for at least the 12 weeks prior to study entry at a dose that, in accordance with local clinical practice, is considered acceptable to adequately assess clinical response. The dose of MTX must have been a stable, unchanging oral dose of 7.5 to 25 mg/week (or the equivalent injectable dose) for at least the 8 weeks prior to study entry. The dose of MTX is expected to remain stable throughout the study and may be adjusted only for safety reasons
a. For patients entering the trial on MTX doses <15 mg/week, there must be clear documentation in the medical record that higher doses of MTX were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines.
b. Local standard of care should be followed for concomitant administration of folic acid.
6. are able to read, understand, and give written informed consent
Exclusion criteria
7. are currently receiving corticosteroids at doses >10 mg of prednisone per day (or equivalent) or have been receiving an unstable dosing regimen of corticosteroids within 2 weeks of study entry or within 6 weeks of planned randomization
8. have started treatment with NSAIDs (for which the NSAID use is intended for treatment of signs and symptoms of RA) within 2 weeks of study entry or within 6 weeks of planned randomization or have been receiving an unstable dosing regimen of NSAIDs within 2 weeks of study entry or within 6 weeks of planned randomization
9. are currently receiving concomitant treatment with MTX, hydroxychloroquine, and sulfasalazine
10. are currently receiving or have received cDMARDs (eg, gold salts, cyclosporine, azathioprine, or any other immunosuppressives) other than MTX, hydroxychloroquine (up to 400 mg/day), or sulfasalazine (up to 3000 mg/day) within 8 weeks prior to study entry
a. Doses of hydroxychloroquine or sulfasalazine should be stable for at least 8 weeks prior to study entry.
b. Immunosuppression related to organ transplantation is not permitted.
11. have received leflunomide in the 12 weeks prior to study entry (or within 4 weeks prior to study entry if the standard 11 days of cholestyramine is used to washout leflunomide)
12. have started a new physiotherapy treatment for RA in the 2 weeks prior to study entry;Please refer to section 8.1.2 (Exclusion criteria) page 37 of the protocol for the complete list.
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 | EUCTR2012-002322-73-NL |
| CCMO | NL42145.048.12 |