The primary objective is to compare the safety and efficacy of multiple doses of ABT-494 versus placebo in moderately to severely active RA subjects on stable background MTX therapy with inadequate response or intolerance to anti-TNF biologic…
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Source
Brief title
Condition
- Musculoskeletal and connective tissue disorders congenital
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Efficacy:
The primary endpoint of this study is the ACR20 response rate at Week 12. ACR20
response rate will be determined based on 20% or greater improvement in Tender
Joint Count (TJC) and Swollen Joint Count (SJC) and >= 3 of the 5 measures of
Patient's Assessment of Pain (VAS), Patient's Global Assessment of Disease
Activity, Physician's Global Assessment of Disease Activity, Patient's
Assessment of Disability (HAQ-DI) or hsCRP. The secondary endpoints of this
study are ACR50/70 response rates at Week 12, the proportion of subjects
achieving low disease activity (LDA) (2.6 <= DAS28 [CRP] < 3.2) or clinical
remission (CR) (DAS28 [CRP] < 2.6), and the proportion of subjects achieving CR
(DAS28 [CRP] < 2.6) at Week 12.
Pharmacokinetics:
For all subjects, PK trough samples will be collected at each visit beginning
on Day 1 (Baseline) through Week 12. For 30% of subjects, in addition to
trough PK samples at each visit, PK samples will be collected on Day 1
(Baseline) and Week 8 at 1, 2, and 3 hours post-morning dose.
Safety:
Safety evaluations include adverse event monitoring, physical examinations,
vital sign measurements, electrocardiogram, and clinical laboratory testing
(hematology, chemistry, and urinalysis) as a measure of safety and tolerability.
Toxicity management guidelines are provided in the protocol.
Secondary outcome
Secondary Efficacy Variables:
* ACR50 and ACR70 response rates at Week 12
* Proportion of subjects achieving low disease activity (LDA) (2.6 <= DAS28
[CRP] < 3.2) or clinical remission (CR) (DAS28 [CRP] < 2.6) at Week 12.
* Proportion of subjects achieving CR based on DAS28 [CRP] < 2.6 at Week 12.
Background summary
ABT-494 is being developed for the treatment of adult patients with moderate to
severe active rheumatoid arthritis (RA). The enhanced selectivity of ABT-494
may offer an improved benefit:risk profile in patients with RA.
Study objective
The primary objective is to compare the safety and efficacy of multiple doses
of ABT-494 versus placebo in moderately to severely active RA subjects on
stable background MTX therapy with inadequate response or intolerance to
anti-TNF biologic therapy.
Study design
This is a Phase 2, randomized, double-blind, parallel-group, placebo-controlled
multicenter study comparing the safety and efficacy of multiple twice daily
(BID) doses of ABT-494 versus placebo administered for 12 weeks in subjects
with moderately to severely active RA who have shown an inadequate response or
intolerance to anti-TNF biologic treatment(s).
Intervention
Subjects will be randomized in a 1:1:1:1:1 fashion to one of 4 doses of ABT-494
or placebo, all administered with stable background MTX therapy.
The following are the treatment groups:
Group 1: take twice a day one capsule of ABT-494 3 mg BID
Group 2: take twice a day one capsule of ABT-494 6 mg BID
Group 3: take twice a day one capsule of ABT-494 12 mg BID
Group 4: take twice a day one capsule of ABT-494 18 mg BID
Group 5: take twice a day one capsule of Placebo BID
Study burden and risks
The prevalence of Rheumatoid arthritis (RA) in the general population is
approximately 1%, and increases with age in both genders, with women being more
prone for developing RA than men. RA subjects who inadequately responded to or
are unable to tolerate an anti-TNF therapy are a subgroup of patients with
significant unmet medical need. We would like to us ABT-494 for this patient
population. The information that is obtained during this study is useful
scientifically and thus be helpful to others with the same condition in the
future.
Knollstrasse 50
Ludwigshafen 67061
DE
Knollstrasse 50
Ludwigshafen 67061
DE
Listed location countries
Age
Inclusion criteria
1. Adult male or female, at least 18 years old.;2. Diagnosed with RA based on either the 1987-revised American College of Rheumatology (ACR)
classification criteria or the 2010 American College of Rheumatology/European League against
Rheumatism (ACR/EULAR) criteria for >= 3 months.;3. Subjects must have been receiving oral or parenteral MTX therapy >= 3 months and on a stable
prescription of 7.5 to 25 mg/week for at least 4 weeks prior to initiating the study drug. Subjects
should also be on a stable dose of folic acid (or equivalent) for at least 4 weeks prior to initiating the study drug. Subjects should continue with their stable doses of MTX and folic acid throughout the study.;4. Subjects have been treated with 1 or 2 anti-TNF biologics for >= 3 months but continue to exhibit
active RA, or had to discontinue due to intolerability or toxicity. In addition, subjects may have
received up to 1 non-anti-TNF biologic (e.g., abatacept, rituximab, anakinra, or tocilizumab) prior
to Screening.;5. Have active RA as defined by the following minimum disease activity criteria:
• >= 6 swollen joints (based on 66 joint counts) at Screening and Baseline Visits.
• >= 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits.
• hs-CRP > Upper Limit of Normal (ULN) OR positive for both rheumatoid factor and anti-CCP
antibody.
Exclusion criteria
A subject will be excluded from the study if he/she meets any of the following criteria:
1. Prior exposure to JAK inhibitor (e.g., tofacitinib, baricitinib).
2. Receipt of any investigational drug of chemical or biologic nature within a minimum of 30 days or 5 half-lives of the drug (whichever is longer) prior to initiating the study drug.
3. Current or expected need of other immunosuppressant medications, except MTX. Use of oral intake of > 10 mg prednisone/day or equivalent corticosteroid therapy.
4. Screening laboratory values meeting the following criteria:
• Serum aspartate transaminase (AST) or alanine transaminase (ALT) > 1.5 × ULN
• Estimated glomerular filtration rate (eGRF) by simplified 4-variable Modification of Diet in
Renal Disease (MDRD) formula < 40 mL/min/1.73 m2
• Total white blood cell count (WBC) < 3,000/µL
• Absolute neutrophil count (ANC) < 1,200 /µL
• Platelet count < 100,000/µL
• Absolute lymphocytes count < 750/µL
• Hemoglobin < 9 gm/dL
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 | EUCTR2013-002358-57-NL |
| ClinicalTrials.gov | NCT01960855 |
| CCMO | NL47690.018.14 |