The primary objective of the study is to determine whether baricitinib 4 mg QD is superior toplacebo in the treatment of patients with moderately to severely active RA who have had an inadequate response to a TNF inhibitor, despite ongoing treatment…
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 4 mg QD
is superior to
placebo in the treatment of patients with moderately to severely active RA who
have had an inadequate response to a TNF inhibitor, despite ongoing treatment
with cDMARDs, as assessed by the proportion of patients achieving a 20%
improvement in American College of Rheumatology Criteria (ACR20) at Week 12.
Secondary outcome
Secondary study parameters/outcome of the study:
The major secondary objectives of the study are:
• to evaluate the efficacy of baricitinib 4 mg QD versus placebo as assessed by:
1. change from baseline to Week 12 in Health Assessment
Questionnaire-Disability Index (HAQ-DI) score
2 change from baseline to Week 12 in Disease Activity Score 28 (DAS28)-high
sensitivity C-reactive protein (hsCRP)
• to evaluate the efficacy of baricitinib 2 mg QD versus placebo as assessed by:
1. proportion of patients achieving ACR20 at Week 12
2. change from baseline to Week 12 in HAQ-DI score
3. change from baseline to Week 12 in DAS28-hsCRP
Please refer to section 6.2 (Secondary Objectives) page 23 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 and 2 mg baricitinib when
administered once a day (QD) to patients with RA who have had an inadequate
response to or are intolerant to at least 1 biologic tumor necrosis factor
(TNF) inhibitor therapy (TNF-IR patients) and who are also taking background
conventional disease-modifying antirheumatic drugs (cDMARDs) (with or without
methotrexate [MTX]). 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 4 mg QD
is superior to
placebo in the treatment of patients with moderately to severely active RA who
have had an inadequate response to a TNF inhibitor, despite ongoing treatment
with cDMARDs, as assessed by the proportion of patients achieving a 20%
improvement in American College of Rheumatology Criteria (ACR20) at Week 12.
Study design
Study JADW will be a Phase 3, multicenter, randomized, double-blind,
double-dummy, placebo-controlled, outpatient study comparing the efficacy of
4-mg and 2-mg QD oral doses of baricitinib versus placebo on signs and symptoms
of RA.
A total of 525 patients will be randomized in a 1:1:1 ratio to 1 of the
following 3 treatment arms: baricitinib 4 mg QD (n=175), baricitinib 2 mg QD
(n=175), or placebo (n=175). All patients will continue on a background of
cDMARDs. Patients with renal impairment, defined as estimated glomerular
filtration rate (eGFR) <60 mL/min/1.73 m2, will receive 2 mg baricitinib QD if
assigned to active treatment. Patients not assigned to receive active treatment
will receive matching placebo. After the Week 24 study visit, eligible patients
may proceed to a separate extension study (Study I4V-MC-JADY) or to the
post-treatment follow-up period of this study (Part B).
Study JADW consists of 3 parts:
• Screening: A screening period lasting from 3 to 42 days prior to Visit 2
(Week 0)
• Part A: A double-blind, placebo-controlled period from Week 0 to Week 24
• Part B: A post-treatment follow-up period.
Planned Duration of Treatment: 24 weeks
Lead-in period: 3 to 42 days
Treatment period: 24 weeks
Follow-up period: 28 days
Intervention
Baricitinib will be administered orally as a 4-mg or 2-mg tablet QD. Patients
not assigned to baricitinib treatment will receive either a 4-mg or 2-mg
matching placebo tablet.
Patients will continue to take their background cDMARD 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.
Baricitini) 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
Windlesham GU20 6PH
GB
Erl Wood Manor, Sunninghill Road
Windlesham GU20 6PH
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 or SJC for entry or enrollment purposes.
4. have a C-reactive protein (or hsCRP) measurement >=1 times the upper limit of normal (ULN) based on the most recent data (if available)
5. have been treated at approved doses with at least 1 biologic TNF-α inhibitor (eg, infliximab, certolizumab, golimumab, etanercept, adalimumab) for at least 3 months and in the opinion of the investigator either:
a. experienced insufficient efficacy or loss of efficacy at a dose that, in accordance with local clinical practice, is considered acceptable to adequately assess clinical response or
b. experienced intolerance of such treatment
6. have had regular use of at least 1 cDMARD 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, as specified below:
a. 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.
b. 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.
c. Local standard of care should be followed for concomitant administration of folic acid.
d. For patients entering the trial while receiving the following DMARDs, the dose must be stable for at least 8 weeks prior to study entry and not exceed the dose listed: hydroxychloroquine up to
400 mg/day; sulfasalazine up to 3000 mg/day; leflunomide (Arava®, Sanofi-Aventis) up to 20 mg/day; and azathioprine up to 150 mg/day or 2 mg/kg/day.
7. are able to read, understand, and give written informed consent
Exclusion criteria
8. have received a biologic treatment for RA such as etanercept, anakinra, infliximab, tocilizumab, certolizumab, adalimumab, golimumab or abatacept within 28 days of planned randomization; have received rituximab within 6 months of planned randomization
9. are currently receiving corticosteroids at doses >10 mg per day of prednisone (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
10. 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
11. are currently receiving concomitant treatment with MTX, hydroxychloroquine, and sulfasalazine
12. have started a new physiotherapy treatment for RA in the 2 weeks prior to study entry
13. have received any parenteral corticosteroid administered by intramuscular or intravenous (IV) injection within 2 weeks prior to study entry or within 6 weeks prior to planned randomization or are anticipated to require parenteral injection of corticosteroids during the study
14. have had 3 or more joints injected with intraarticular corticosteroids within 2 weeks prior to study entry or within 6 weeks prior to planned randomization
a. Joints injected with intraarticular corticosteroids within 2 weeks prior to study entry or within 6 weeks prior to planned randomization cannot be counted in the TJC and SJC for entry or enrollment purposes.
15. have active fibromyalgia, that in the investigator*s opinion, would make it difficult to appropriately assess RA activity for the purposes of this study;Please refer to section 8.1.2 (Exclusion criteria) page 30 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 | EUCTR2012-002323-15-NL |
| CCMO | NL42146.048.12 |