Clinical Trials

Date: 2015-07-08

Type of information: Publication of results in a medical journal

phase: 2b

Announcement: publication of results in The New English Journal of Medicine

Company: Janssen Research & Development, a J&J company (USA - NJ)

Product: guselkumab (CNTO 1959)

Action mechanism:

• monoclonal antibody. Guselkumab is a human monoclonal antibody that targets interleukin (IL)-23, and is in Phase 3 clinical development as a subcutaneously administered therapy for the treatment of moderate to severe plaque psoriasis.
•  This antibody was generated utilizing the HuCAL antibody library technology licensed from MorphoSys.

Disease: psoriasis

Therapeutic area: Autoimmune diseases - Dermatological diseases

Country: Belgium, Canada, Germany, Poland, USA

Trial details:

• X-PLORE is a Phase 2b, randomized, placebo- and active comparator-controlled, parallel-group, multicenter dose-ranging study. The trial investigated subcutaneous injections of five doses of guselkumab compared with placebo and adalimumab in patients with moderate to severe plaque psoriasis, defined by a PASI greater than or equal to 12, PGA greater than or equal to 3 and body surface area (BSA) involvement of at least 10 percent, who are candidates for systemic or phototherapy. Patients (n=293) were randomized in the seven-arm study to receive placebo, guselkumab (five dose groups: 5 mg at weeks 0, 4 then every 12 weeks; 15 mg every eight weeks; 50 mg at weeks 0, 4 then every 12 weeks; 100 mg every eight weeks; and 200 mg at weeks 0, 4 then every 12 weeks), or adalimumab (80 mg initial dose, followed by 40 mg every other week starting one week after initial dose). The primary endpoint was the proportion of patients who achieve a Physician\'s Global Assessment (PGA) score of cleared (0) or minimal (1) at week 16. A PGA score indicates a physician\'s assessment of the severity of psoriasis, with 0 indicating no psoriasis (clear of disease) and 5 indicating most severe disease. Secondary endpoints include at least a 75 percent or 90 percent improvement in psoriasis as measured by the Psoriasis Area Severity Index (PASI 75 or PASI 90) at week 16.  (NCT01483599)

Latest news:

• • On July 8, 2015, Johnson&Johnson announced that results published in The New England Journal of Medicine from a Janssen Research & Development-sponsored Phase 2b trial showed up to 86 percent of patients with moderate to severe plaque psoriasis receiving guselkumab (CNTO 1959) achieved a Physician\'s Global Assessment (PGA) score of cleared psoriasis or minimal psoriasis at week 16, the study\'s primary endpoint. The X-PLORE study showed significantly higher levels of efficacy for all guselkumab doses at week 16 when compared with the placebo group, and responses were maintained through week 40 of the study. The trial also included an active comparator arm, which showed several guselkumab dosage regimens provided better response rates compared with the anti-tumor necrosis factor (TNF)-alpha agent, adalimumab (Humira®).
• X-PLORE is a Phase 2b, randomized, placebo- and active comparator-controlled, parallel-group, multicenter dose-ranging seven-arm study in which participants received subcutaneous injections of either placebo, guselkumab (five dose groups: 5 mg at weeks 0, 4 then every 12 weeks; 15 mg every eight weeks; 50 mg at weeks 0, 4 then every 12 weeks; 100 mg every eight weeks; and 200 mg at weeks 0, 4 then every 12 weeks) or adalimumab (80 mg initial dose, followed by 40 mg every other week starting one week after initial dose). At week 16, significantly higher proportions of guselkumab-treated patients achieved PGA 0 (cleared psoriasis) or 1 (minimal psoriasis) compared with patients receiving placebo across all dose groups: 34 percent (5 mg); 61 percent (15 mg); 79 percent (50 mg); 86 percent (100 mg); 83 percent (200 mg); 7 percent (placebo group) [P = 0.002 for 5 mg; P < 0.001 for all other doses]. According to major secondary endpoints, at week 16, significantly higher proportions of patients receiving guselkumab achieved at least a 75 percent or 90 percent improvement in the Psoriasis Area Severity Index (PASI 75 or PASI 90, respectively): 44 percent and 34 percent, respectively (5 mg); 76 percent and 34 percent, respectively (15 mg); 81 percent and 45 percent, respectively (50 mg); 79 percent and 62 percent, respectively (100 mg); and 81 percent and 57 percent, respectively (200 mg), compared with 5 percent and 2 percent, respectively (placebo group) [P < 0.001]. Patients in all guselkumab groups achieved significantly greater decreases (improvement) in Dermatology Life Quality Index (DLQI) score from baseline to week 16 compared with placebo (P ? 0.008). After week 16, the proportions of guselkumab-treated patients achieving a PGA score of 0 or 1, PASI 75 and PASI 90 remained consistent or showed additional improvement. Moreover, complete clearance (PGA 0 and PASI 100) was observed in 62 percent and 54 percent, respectively, of patients in the guselkumab 100 mg dose group after 40 weeks of continuous treatment. Guselkumab at doses of 50 mg, 100 mg and 200 mg showed higher efficacy when compared with the adalimumab treatment group. Significantly greater proportions of patients in the guselkumab 50 mg, 100 mg and 200 mg groups achieved a PGA score of 0 or 1 at week 16 compared with the adalimumab group (58 percent). Similarly, significantly greater proportions of guselkumab-treated patients in the 50 mg (71 percent), 100 mg (77 percent) and 200 mg (81 percent) groups achieved a PGA score of 0 or 1 at week 40 than the adalimumab-treated group (49 percent). Through week 16, the placebo-controlled period, adverse events (AEs) were reported in 50 percent of patients receiving guselkumab (combined groups), 56 percent of patients receiving adalimumab and 52 percent of patients receiving placebo; 1 percent, 2 percent and 2 percent of patients reported at least one serious AE in these respective groups. Serious infections occurred in two patients treated with guselkumab (appendicitis, lung abscess). Between week 16 and week 52, AEs were reported in 49 percent of patients receiving guselkumab (combined groups) and 61 percent of patients receiving adalimumab; 2 percent and 3 percent reported at least one serious AE in these respective groups. No additional serious infections occurred in guselkumab-treated patients; one serious infection occurred in a patient treated with adalimumab (pneumonia). There were no cases of tuberculosis or opportunistic infections. One guselkumab-treated patient reported a malignancy (cervical intraepithelial neoplasia III, including carcinoma in situ). Three major adverse cardiovascular events were reported in guselkumab-treated patients (one fatal myocardial infarction [MI], one nonfatal MI, one cerebrovascular accident), all of whom had multiple pre-existing cardiovascular risk factors.
• (A Phase 2 Trial of Guselkumab versus Adalimumab for Plaque Psoriasis. Kenneth B. Gordon, M.D., Kristina Callis Duffin, M.D., Robert Bissonnette, M.D., Jörg C. Prinz, M.D., Yasmine Wasfi, M.D., Ph.D., Shu Li, Ph.D., Yaung-Kaung Shen, Ph.D., Philippe Szapary, M.D., M.S.C.E., Bruce Randazzo, M.D., Ph.D., and Kristian Reich, M.D., Ph.D.. N Engl J Med 2015; 373:136-144July 9, 2015DOI: 10.1056/NEJMoa1501646)

 

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