Background ASP015K is a novel oral Janus kinase (JAK) inhibitor in development for the treatment of rheumatoid arthritis (RA). ASP015K inhibits JAK1/3 with more selectivity over JAK2 and can be dosed once daily (QD).
Objectives To evaluate the efficacy, safety and dose response of ASP015K monotherapy in Japanese patients with moderate to severe RA (Clinical Trials Registration: NCT01649999).
Methods In a 12-week, double-blind study, patients 20 years or older with active RA (defined as either CRP >0.5 mg/dL or ESR ≥28 mm/hr and ≥6 tender joints (of 68) and ≥6 swollen joints (of 66)) not on concomitant DMARD therapy were randomized equally to once daily ASP015K 25 mg, 50 mg, 100 mg, 150 mg or placebo (PBO). The primary endpoint was ACR20-CRP response at week12 or early termination (week12/ET).
Results 281 patients were randomized and dosed; 81.1% of patients were female, the mean age was 53.0 years, and 25.3% had previously used an anti-TNF therapy. At baseline, the mean tender joint count was 15.2, the mean swollen joint count 12.2, the mean CRP 2.41 mg/dL, and the mean ESR 48.0 mm/hr. ASP015K 50 mg, 100 mg and 150 mg each showed a statistically significantly higher ACR20-CRP response at week12/ET as compared to PBO and the response rates increased up to 150 mg. ACR50/70 response and DAS28-CRP remission were significantly higher in the 2 highest dose groups as compared to PBO. Dose-dependent improvement in DAS28-CRP was also seen.
The incidence of adverse events (AEs) was similar between PBO and combined ASP015K groups (64.3% vs 64.0%). The most frequently reported AEs in the combined ASP015K groups as compared to PBO were nasopharyngitis (13.3% vs 5.4%), RA (12.4% vs 32.1%), blood creatine phosphokinase (CPK) increased (4.9% vs 0%), and diarrhoea (3.6% vs 1.8%).
These CPK increases tended to be transient, and patients recovered without interruption of study drug treatment. The overall incidence of infections and serious adverse events were similar between placebo and ASP015K (21.4% vs 24.9% and 1.8% vs 2.7%, respectively). One study-drug unrelated death due to a cerebral haemorrhage occurred in the ASP015K 50 mg group. The safety profile was generally comparable among the ASP015K dose groups, with the highest dose having a higher rate of blood CPK increase AEs.
Conclusions In Japanese patients, treatment with ASP015K as monotherapy for 12 weeks is well tolerated and efficacious. These data support further development of ASP015K for the treatment of RA.
Disclosure of Interest T. Takeuchi Grant/research support: AbbVie, Astellas, BMS, Chugai, Daiichi-Sankyo, Eisai, Janssen, Mitsubishi-Tanabe, Nippon-Shinyaku, Otsuka, Pfizer, Sanofi, Santen, Takeda, Teijin, Consultant for: Astellas, AstraZeneca, Eli Lilly, Novartis, Mitsubishi-Tanabe, Asahi Kasei, Speakers bureau: AbbVie, BMS, Chugai, Eisai, Janssen, Mitsubishi-Tanabe, Pfizer, Takeda, Y. Tanaka Grant/research support: BMS, MSD, Chugai, Mitsubishi-Tanabe, Astellas, AbbVie, Eisai, Janssen, Speakers bureau: Mitsubishi-Tanabe, AbbVie, Eisai, Chugai, Janssen, Santen, Pfizer, Astellas, Daiichi-Sankyo, GSK, AstraZeneca, Otsuka, Actelion, Eli Lilly, Nippon Kayaku, Quintiles Transnational, Ono, UCB Pharma, M. Iwasaki Consultant for: Astellas, H. Ishikura Employee of: Astellas, S. Saeki Employee of: Astellas, Y. Kaneko Employee of: Astellas, J. Garg Employee of: Astellas