Trial Results

Promising Crohn’s Therapy

August 6, 2018

RedHill Biopharma announced positive top-line safety and efficacy results from the first Phase III study with RHB-104 for Crohn’s disease (the MAP US study). The study successfully met its primary and key secondary endpoints. Top-line results in the intent-to-treat (ITT) population demonstrated superiority of RHB-104 over placebo in achieving remission at week 26, defined as Crohn’s Disease Active Index (CDAI) value of less than 150, the primary endpoint of the study. The proportion of patients meeting the primary endpoint was significantly greater in the RHB-104 group compared to placebo (37 percent vs. 23 percent, p= 0.013). The study also successfully met key secondary endpoints, demonstrating consistent benefit to Crohn’s disease patients treated with RHB-104. The MAP US randomized, double-blind, placebo-controlled first Phase III study of RHB-104 included 331 subjects with moderately to severely active Crohn’s disease in the U.S., Canada, Europe, Australia, New Zealand and Israel. Subjects were randomized 1:1 to receive RHB-104 or placebo in addition to baseline background medication including of 5-ASAs, corticosteroids, immunomodulatorsor anti-TNFα agents. RHB-104 was found to be generally safe and well tolerated. Top-line results demonstrated that the active and placebo treatment groups experienced similarly low rates of serious adverse events and treatment emergent adverse events, indicating a positive safety profile for RHB-104.

Positive Results, Duputren’s Therapy
180 Therapeutics LP announced positive results from a Phase IIa clinical trial of the anti-TNF monoclonal antibody, adalimumab, in patients suffering from Dupuytren’s disease. The randomized, dose response, placebo-controlled Phase IIa trial involved 28 patients with Dupuytren’s disease who were scheduled to receive elective surgery to remove diseased tissue from their hands. They received either a placebo or a single injection of the anti-TNF drug, adalimumab, at various dose levels, two weeks before scheduled surgery. The tissue removed during surgery was then analyzed in the laboratory. Adalimumab, at a dose of 40mg, reduced expression of the fibrotic markers, α-smooth muscle actin (α-SMA) and type I procollagen proteins, at two weeks post injection, suggesting anti-TNF therapy may help treat early Dupuytren’s disease by blocking activity of disease-causing myofibroblast cells. The dose-ranging study found that injection of the anti-TNF druginto Dupuytren’s disease nodules reduced key cellular fibrosis markers. The treatment was found to be well-tolerated.

First Patient Dosing in STRIDE 3
Kala Pharmaceuticals announced that the first patient has been dosed in STRIDE 3 (Short Term Relief in Dry Eye), its Phase III trial of KPI-121 0.25% for the short-term treatment of dry eye disease. The STRIDE 3 trial is a multicenter, randomized, double-blind, placebo controlled, parallel-arm study comparing KPI-121 0.25% to placebo, each dosed four times a day (QID) for 14 days, in approximately 900 patients with dry eye disease. Subjects who meet initial screening and inclusion/exclusion criteria undergo a two-week run-in period with placebo. Subjects who continue to meet inclusion/exclusion criteria after the run-in are randomized to either KPI-121 0.25% or placebo. The primary endpoint, Day 15 ocular discomfort severity, is based upon a patient diary in which ocular discomfort is recorded daily over the entire course of the trial using a visual analog grading scale. KPI-121 0.25% achieved statistical significance for the primary sign endpoint of conjunctival hyperemia at Day 15 in the intent to treat (ITT) population in both Phase III trials. KPI-121 0.25% was well-tolerated in both Phase III trials with elevation in intra-ocular pressure, a known side effect with topical corticosteroids, similar to placebo.

NVAMD Trial Encouraging
RXi Pharmaceuticals Corporation announced positive results with RXI-109 in a Phase I/II clinical trial. RXI-109-1501 is an open-label, multi-dose, dose escalation study with three dose cohorts, enrolled sequentially, evaluating the safety and tolerability of RXI-109 injections in the eye of subjects with advanced neovascular age-related macular degeneration (NVAMD) or ‘wet’ age-related macular degeneration, and accompanying subretinal fibrosis. During this study, the clinical effect of these injections was evaluated as a secondary endpoint. Nine subjects were enrolled, three in each of the following dosage groups: Cohort 1 (low dose), Cohort 2 (intermediate dose), Cohort 3 (high dose). Each subject received a total of four doses of RXI-109 at one-month intervals. RXI-109 was administered by intravitreal injection in one eye only. The dosing period (three months) was followed by a four-month observation period. In total, 25 AEs were reported, 13 in Cohort 1, seven in Cohort 2 and five in Cohort 3. The severity of all these AEs was either mild or moderate: 18 of these AEs were considered mild and the other seven AEs were considered moderate. The primary objective of this study was to evaluate the safety and tolerability of ocular injections with RXI-109. The primary objective was met as shown by the absence of dose-limiting and serious toxicities, and only mild to moderate procedure related adverse events. None of the adverse events were drug- related. In addition, comprehensive ocular examinations showed no indications of inflammation or other tolerability issues related to the treatment, indicating RXI-109 was safe and well tolerated by patients in the three dosage groups.