Treatment of plaque-type psoriasis with oral CF101: Data from a phase II/III multicenter, randomized, controlled trial

Michael David, Dimitar Konstantinov Gospodinov, Nicola Gheorghe, Grisha Stefanov Mateev, Mariyana Venelinova Rusinova, Evgeniya Hristakieva, Laura Gheuca Solovastru, Rita V. Patel, Calin Giurcaneanu, Mariela Chepileva Hitova, Anca Ioana Purcaru, Beti Horia, Iliya Iliev Tsingov, Rumyana Kaloferova Yankova, Miroslava Ilieva Kadurina, Michal Ramon, Maria Rotaru, Olga Simionescu, Vasile Benea, Zdravka Velichkova DemerdjievaMaria Rodica Cosgarea, Horia Silviu Morariu, Ziv Michael, Patricia Cristodor, Carmen Nica, Michael H. Silverman, David R. Bristol, Zivit Harpaz, Motti Farbstein, Shira Cohen, Pnina Fishman

Research output: Contribution to journalArticlepeer-review

Abstract

Background: 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. OBJECTIVE: To evaluate the safety and efficacy of CF101 treatment in a Phase 2/3 study in patients with moderate to severe plaque-type psoriasis. METHODS: 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. Results: 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%). Conclusions: 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.

Original languageEnglish
Pages (from-to)931-938
Number of pages8
JournalJournal of Drugs in Dermatology
Volume15
Issue number8
StatePublished - Aug 2016
Externally publishedYes

Fingerprint

Dive into the research topics of 'Treatment of plaque-type psoriasis with oral CF101: Data from a phase II/III multicenter, randomized, controlled trial'. Together they form a unique fingerprint.

Cite this