Clinical Trials

Date: 2016-05-31

Type of information: Results

phase: 2a

Announcement: results

Company: Innovation Pharmaceuticals (USA - MA)

Product: prurisol

Action mechanism:

• Prurisol is a small molecule that acts through immune modulation and PRINS reduction. In laboratory studies, prurisol was found to be effective against psoriasis in animal models, both in induced psoriasis as well as in a xenograft model using human psoriatic tissue. Prurisol eliminated virtually all signs of psoriasis with no reoccurrence of the lesions. Prurisol is synthesized through a five-step process using commercially available starting materials.

Disease: moderate chronic plaque psoriasis

Therapeutic area: Autoimmune diseases - Dermatological diseases

Country: USA

Trial details:

• The randomized, double-blind study consists of four arms, with the three active arms receiving different dosing levels of oral Prurisol daily and the fourth arm receiving only placebo daily. The primary efficacy endpoint will be the percentage of subjects with ? 2 point improvement in Investigator’s Global Assessment (IGA) rating as defined by visual inspections of psoriasis lesions over a period of up to 84 days. (NCT02494479)

Latest news:  

• • On May 31, 2016, Cellceutix announced that the pharmacokinetics (PK) data on the recently completed Phase 2 trial of prurisol as a novel oral treatment for plaque psoriasis has been received and is starting to be analyzed. The PK data complements the efficacy data reported last week (see below) by showing a dose-dependent increase in exposure and maximum plasma concentration of the drug. Further, the elimination half-life was similar in each of the three dosing levels (50mg, 100mg, 200mg), with an average of 1.3 hours. The clearance of the drug was also similar across dosing levels, with an average of 80.1 liters per hour.
• Of particular note, the half-life of prurisol is shorter than that of apremilast (Otezla®) (1.3 hours vs. 6 to 9 hours). This suggests prurisol, which acts through immunodulatory mechanisms, may not be dependent upon long-term exposure in the body to exhibit activity. A shorter half-life also may play a role in minimizing side effects commonly observed with other psoriasis treatments. The longer the drug remains in the body, the greater potential for adverse interactions with other medications and foods.
• Low Patient Dropout Rates: Patient withdrawals from study arms, whether active or placebo, are often an indicator of general patient satisfaction or dissatisfaction of the drug under study. Additional data analyses revealed a higher dropout rate among patients on placebo compared to patients receiving Prurisol.
• • On May 24, 2016, Cellceutix Corporation announced that topline data from the company’s Phase 2 FDA trial of orally-administered prurisol in the treatment of mild to moderate chronic plaque psoriasis have been compiled and reviewed. The trial successfully achieved its primary endpoint, further validating Prurisol’s potential as a novel oral treatment for psoriasis.
• Study Background: Enrolling 115 patients, the placebo-controlled, randomized, double-blind trial tested the efficacy and safety of three separate, twice-daily, dosing regimens of Prurisol—50 milligram (mg) (50mg QD), 100mg (50mg BD), and 200mg (100mg BD). All patients were assessed via the 5-point Investigator’s Global Assessment (IGA) scale, ranging from a score of 0 (“clear”) to a score of 4 (“severe”).
• Entry criteria for the study required: a total Body Surface Area (BSA) affected by plaque psoriasis of 10 percent to 20 percent; a baseline IGA score of 2 (“mild”) or 3 (“moderate”); and the identification of a target psoriatic lesion with a score greater than or equal to 3 based on a different (than the IGA) lesion-specific 5-point scoring scale. Clinical signs that psoriasis is clearing typically are more noticeable in patients with a greater severity of symptoms. This translated into a rigorous and aggressive study design for the Prurisol trial.
• The primary endpoint assessed was the percentage of patients achieving at least a 2-point improvement from baseline on the IGA 5-point scale as measured by visual inspection of patient lesions at the end of the 84-day (12-week) treatment period. In effect, given the entry criteria, participants had to at least obtain an IGA score of “clear” or “almost clear” skin, dropping to 0 or 1 after starting from a baseline of 2 or 3. Secondary endpoints included additional improvement measures tied to degree of patient response at various time intervals.
• Results Summary The Phase 2 prurisol trial, while not powered to demonstrate statistical significance, was conducted to inform any future fully-powered Phase 3 trial(s) that might be merited. As a result, the study’s main goal was to provide indications of efficacy, safety and tolerability upon treating patients with mild to moderate plaque psoriasis via oral delivery.
• Overall analyses showed prurisol to be superior to placebo in the 200mg arm. Pharmacokinetics/Pharmacodynamics (PK/PD) further revealed an early (by week 8) dose-related response that improved as treatment duration increased. Evaluating the primary endpoint at 84-days (week  12) in the 200mg arm, 35.0% of the patients receiving that dose of Prurisol demonstrated clinically significant improvements compared with 16.7% of patients on placebo only. This percentage includes patient data from one site where investigator non-compliance may have occurred. Were that site to have been excluded from overall data analysis, as is done in some clinical studies (refer to the journal article linked to below, published findings from another psoriasis study), 43.7% of patients in the 200mg prurisol arm would have met the primary endpoint. Patient responses in the 50mg and 100mg arms were statistically comparable to the placebo arm.
• Sub-population analyses further showed greater efficacy demonstrated in patients who had a baseline IGA score of 3 (“moderate”) as compared to those with a baseline score of 2 (“mild”). Some of these patients even experienced a 3-point reduction in their IGA score, going from “moderate” to “clear.” This suggests prurisol may be more effective in treating moderate to severe psoriasis patients to a greater degree than those patients who exhibit less severe symptoms. In moderate to severe psoriasis studies, the placebo response also tends to be lower.
• Regarding prurisol’s safety profile, only a single Serious Adverse Event (SAE) was reported in the study, that being in the 50mg arm, with the type and the rate of occurrence of additional Adverse Events (AEs) similar and evenly distributed across all the three dosing arms and the placebo arm. Additional detailed data review and analysis is underway and an end-of-Phase 2 meeting with the FDA will be requested to help determine the dose(s) and design for future studies, which may include higher dosing regimens to determine Prurisol’s maximum therapeutic effect. The Company plans to release other summary findings from this trial in the coming months, with full results anticipated to be submitted for journal publication and presentation at a future medical congress.
• • On May 11, 2016, Cellceutix Corporation announced that the clinical database for the Phase 2 clinical trial of prurisol for the treatment of mild-to-moderate chronic plaque psoriasis is expected to be “unblinded” next week. Once the blind is removed, data from each of the four arms of the trial (one placebo arm, three oral dosing regimens of Prurisol) will be reviewed and analyzed to evaluate the safety and efficacy of Prurisol. Cellceutix expects to release top-line data from the study approximately one week after the blind is removed.
• • On March 17, 2016, Cellceutix announced the conclusion of the last patient visit in the Phase 2 trial of prurisol for the treatment of mild to moderate chronic plaque psoriasis. The unblinding of the study and top-line data is expected to be available in May. Although the data is still blinded, there were no safety items of concern.
• • On March 1, 2016, Cellceutix announced that dosing has been completed in thePhase 2 trial of prurisol for the treatment of mild to moderate chronic plaque psoriasis.
• • On January 25, 2016, Cellceutix Corporation announced that approximately 75 percent of the subjects enrolled in the company’s Phase 2 clinical trial of Prurisol for the treatment of chronic plaque psoriasis have completed dosing, defined as 84 days of daily treatments of prurisol or placebo. The subjects will now be followed for an additional 4 weeks, without taking any further study medication. The trial was expected to enroll 100 subjects and actually enrolled 115 subjects. The final study visit for the last subject is expected early in April 2016, with top-line data anticipated approximately four weeks later.
• • On September 30, 2015, Cellceutix Corporation announced that its Phase 2 clinical trial of prurisol for psoriasis has now enrolled approximately 50 percent of the planned number of patients. The trial was designed to enroll 100 patients with active mild to moderate chronic plaque psoriasis. Enrollment is expected to be completed by the end of 2015.
• • On August 6, 2015, Cellceutix Corporation announced the commencement of a phase 2 trial of prurisol for the treatment of plaque psoriasis. The multi-center Phase 2 trial is designed to assess the efficacy and safety of Prurisol given orally compared to placebo in a randomized, double-blind setting in patients with mild to moderate chronic plaque psoriasis. The trial is expected to enroll 100 subjects. The primary efficacy endpoint will be the percentage of subjects with greater than or equal to a 2-point improvement in Investigator’s Global Assessment (IGA) rating as defined by visual inspections of patient lesions.

   

Is general: Yes