David Michael, Gospodinov Dimitar Konstantinov, Gheorghe Nicola, Mateev Grisha Stefanov, Rusinova Mariyana Venelinova, Hristakieva Evgeniya, Solovastru Laura Gheuca, Patel Rita V, Giurcaneanu Calin, Hitova Mariela Chepileva, Purcaru Anca Ioana, Horia Beti, Tsingov Iliya Iliev, Yankova Rumyana Kaloferova, Kadurina Miroslava Ilieva, Ramon Michal, Rotaru Maria, Simionescu Olga, Benea Vasile, Demerdjieva Zdravka Velichkova, Cosgarea Maria Rodica, Morariu Horia Silviu, Michael Ziv, Cristodor Patricia, Nica Carmen, Silverman Michael H, Bristol David R, Harpaz Zivit, Farbstein Motti, Cohen Shira, Fishman Pnina
J Drugs Dermatol. 2016 Aug 1;15(8):931-8.
CF101, an adenosine A3 receptor agonist, is an orally bioavailable small molecule drug presenting an anti-psoriatic effect demonstrated in a Phase 2 clinical trial in psoriasis patients.
To evaluate the safety and efficacy of CF101 treatment in a Phase 2/3 study in patients with moderate to severe plaque-type psoriasis.
This multicenter, double-blind, 2-segment, placebo-controlled study randomized subjects with moderate to severe plaque psoriasis to CF101 1 or 2 mg, or placebo twice daily. At either week 12 (Segment 1) or 16 (Segment 2), the placebo group crossed over to CF101 BID through week 32 in an open-label fashion. At week 12, following an interim analysis, the CF101 1mg group was discontinued due to futility. The primary endpoint was proportion of patients achieving ≥75% improvement in Psoriasis Area Severity Index (PASI 75). Efficacy testing was performed using the Cochran-Mantel Haenszel test, the primary analysis of PASI 75 was performed at the 0.035 significance level.
CF101 had an excellent safety profile at all tested dosages with a profile similar to the placebo group. The most common adverse events were infections and gastrointestinal events, and there was no cumulative intolerance over the 32-week dosing period. The study did not meet the primary endpoint of PASI 75 at week 12 (2 mg: 8.5% vs. placebo: 6.9%, P=0.621). However, at week 32, PASI mean percent improvement with CF101 2 mg was 57% (P<0.001) compared to baseline, with linear improvement in PASI 50 (63.5%), 75 (35.5%), 90 (24.7%), and 100 (10.6%).
Oral CF101 was found to be safe and very well tolerated, demonstrating evidence of efficacy in patients with moderate to severe plaque psoriasis through 32 weeks of treatment.
J Drugs Dermatol. 2016;15(8):931-938.
CF101是一种腺苷A3受体激动剂，是一种口服生物可利用的小分子药物，在银屑病患者的2期临床试验中显示出抗银屑病作用。
在一项2/3期研究中评估CF101治疗中度至重度斑块型银屑病患者的安全性和有效性。
这项多中心、双盲、2阶段、安慰剂对照研究将中度至重度斑块状银屑病患者随机分为CF101 1或2 mg组，或安慰剂组，每日两次。在第12周（第1阶段）或第16周（第2阶段），安慰剂组以开放标签方式交叉至CF101每日两次给药至第32周。在第12周进行中期分析后，CF101 1mg组因无效而停药。主要终点是银屑病面积和严重程度指数（PASI 75）改善≥75%的患者比例。使用 Cochr an-Mantel Haenszel检验进行疗效测试，PASI 75的主要分析在0.035显著性水平进行。
CF101在所有测试剂量下均具有良好的安全性，其安全性与安慰剂组相似。最常见的不良事件是感染和胃肠道事件，在32周的给药期内没有累积不耐受情况。该研究在第12周未达到PASI 75的主要终点（2 mg：8.5% vs.安慰剂：6.9%，P = 0.621）。然而，在第32周，与基线相比，CF101 2 mg的PASI平均改善百分比为57%（P＜0.001），PASI 50（63.5%）、75（35.5%）、90（24.7%）和100（10.6%）呈线性改善。
口服CF101被发现是安全的且耐受性良好，通过32周的治疗证明对中度至重度斑块型银屑病患者有效。
《皮肤药物杂志》。2016年；15(8):931 - 938。
