The Controlled Trial of Apremilast for Rheumatoid Arthritis Treatment (CARAT)
The purpose of this study is to compare the effects of apremilast with a placebo (an inactive substance that looks like apremilast) on you and other people with rheumatoid arthritis.
The investigators will be collecting information in this study to help us determine -
- the safety of apremilast in patients with active rheumatoid arthritis
- how long it takes for patients with active rheumatoid arthritis to respond to apremilast
- how long the effects of apremilast last after the treatment has ended.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||The Controlled Trial of Apremilast for Rheumatoid Arthritis Treatment|
- To determine the time to response for subjects with active RA taking apremilast (30 mg per os [PO], twice per day [BID]) [ Time Frame: 1.5 years ] [ Designated as safety issue: No ]
- Determine time to flare when apremilast is withdrawn [ Time Frame: 1.5 years ] [ Designated as safety issue: No ]
- Assess the efficacy and magnitude of response to apremilast in active RA measured by ACR 20, 50, & 70 response rates [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Assess safety of apremilast in subjects with active RA [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]Review of labs and possible adverse effects of study drug including Data Safety Monitoring Committee analysis.
|Study Start Date:||May 2010|
|Estimated Study Completion Date:||October 2013|
|Estimated Primary Completion Date:||October 2013 (Final data collection date for primary outcome measure)|
|Active Comparator: 2||
30 mg BID apremilast taken orally for the first 12 weeks followed by responders randomized to either 30 mg BID apremilast (oral) or 30 mg BID placebo (oral) for 8 weeks
Placebo Comparator: Apremilast
Placebo Compared to apremilast arm
Many manifestations associated with RA result from, or are significantly influenced by, the effects of pro-inflammatory cytokines (e.g., TNF, IL-1, IL-6). Specific inhibition of these cytokines with newer, parenterally administered biologic agents has revolutionized the treatment of RA. Apremilast is a novel, orally administered drug which approaches the reduction of pro-inflammatory cytokines via inhibition of phosphodiesterase type 4 (PDE4).
Apremilast, Acetamide, N-[2-[ (1S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl) ethyl]-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl] is a phosphodiesterase type 4 (PDE4) inhibitor under development for use in the treatment of inflammatory conditions.
PDE4 is one of the major phosphodiesterases expressed in leukocytes. Inhibitors of PDE4 cause accumulation of intracellular cyclic adenosine monophosphate (cAMP), which in turn activates protein kinase A and other downstream effectors, resulting in inhibition of pro-inflammatory cytokine transcription and other cellular responses such as neutrophil degranulation, chemotaxis, and adhesion to endothelial cells.
In human cellular models, apremilast inhibited production of inflammatory mediators such as TNF-α, IL-12, IL-2, IFN-γ, IL-5, IL-8, leukotriene B4 (LTB4), and the adhesion molecule CD18/CD11b (Mac-1).
Apremilast has also been shown to be a potent anti-inflammatory agent in several animal models of inflammation.
|Contact: Shelley Moore||214-987-1253||Shelley.Moore@Baylorhealth.edu|
|United States, Texas|
|Baylor Research Institute - Arthritis Care and Research Center||Recruiting|
|Dallas, Texas, United States, 75231|
|Contact: Shelley Moore 214-987-1253 Shelley.Moore@Baylorhealth.edu|
|Sub-Investigator: Kathryn Dao, MD|
|Sub-Investigator: Leilani Law, RN, ANP|
|Principal Investigator:||John Cush, MD||Baylor Research Institute|