Date: 2011-06-04
Type of information:
phase: 2
Announcement: initial results
Company: Hybrigenics (France)
Product: inecalcitol
Action mechanism: Inecalcitol is a synthetic chemical derivative of calcitriol, the naturally active form of vitamin D.
Disease: psoriasis
Therapeutic area: Autoimmune diseases - Dermatological diseases
Country: France
Trial details: The study is conducted by Professor Jean-Paul Ortonne in the Dermatology Department of the University Hospital of Nice, France. It is a double-blinded and placebo-controlled trial comparing inecalcitol in 40 patients vs. placebo in 20 patients. Inecalcitol is given orally at 4 milligrams per day during 16 weeks. The first 20 patients have been enrolled since November 7th and are currently screened before random assignment to the placebo or inecalcitol-treated groups. The enrollment speed could allow the inclusion and treatment of all the 60 patients in due time for a total study duration of less than a year.
Latest
news: * On June 4, 2012, Hybrigenics, a bio-pharmaceutical company with a focus on research and development of new treatments against proliferative diseases, has announced the first results of the placebo-controlled double-blind clinical Phase II efficacy study of oral inecalcitol at the single dose of 4 mg per day in moderate to severe psoriasis.
The primary endpoint was the Psoriasis Area and Severity Index (PASI) which is a composite scoring system taking into account the area of the psoriatic lesions and their thickness, redness and scaling. A patient is considered as a “responder” if his PASI has been decreased by at least 50% during treatment (PASI 50). A PASI decline of more than 75% (PASI 75) is considered clinically relevant.
Of the total 60 enrolled patients, 57 (20 placebo and 37 inecalcitol) have completed their treatment for at least 10 weeks and up to 16 weeks. One early study withdrawal was due to grade 3 hypercalcemia caused by inecalcitol within the first week of treatment. Of the 37 patients treated with oral inecalcitol, 24 patients (65%) showed a PASI 50 response and, among them, 10 patients (27%) had a PASI 75 clinical improvement. However, these results were not statistically different from the placebo group, in which women had an unexpectedly strong improvement of their disease with a PASI 75 rate of 63% vs. 17% observed in placebo-treated men, which is more in line with usual values from the literature on psoriasis studies of similar duration.
Blood levels of inflammatory biomarkers such as IL-4, IL-10, IL-12, IL-17, interferongamma (IFN-?) and tumor necrosis factor alpha (TNF-?) are currently being assayed in samples from all patients, as well as the levels of vitamin D receptor in white blood cells. Biopsies of skin lesions have been taken in subsets of patients and their histopathological examination is also ongoing. This additional data will be available in the coming weeks and may shed some light on the reasons for the strong placebo effect observed in women, and why there weren’t more PASI 50 responders progressing to PASI 75 clinical improvement. In addition, levels of parathyroid hormone (parathormone, PTH) were measured, since PTH levels had decreased below the lower limit of the normal range, and sometimes even below the limit of quantification (LoQ), in all prostate cancer patients treated by 4 mg per day of oral inecalcitol in a clinical tolerance Phase IIa study. During the entire treatment period (16 weeks) and still one month later, after the follow-up period, the PTH levels of each of the 20 patients on placebo changed by less than 50% from their initial value and remained within the normal range. By contrast, the PTH levels of each of the 37 patients receiving inecalcitol decreased by more than 50% during the treatment. PTH levels were decreased below the normal range in 34 inecalcitol-treated patients (92%) and below LoQ in 24 of them (65%). This PTH lowering effect was highly statistically significant as compared with placebo at all times during treatment (p< 0.001), even as soon as week 4, the earliest time point measured. This pharmacological effect of inecalcitol was totally and rapidly reversible because all PTH levels were back within the normal range after the one-month followup period.
* On December 19, 2011, Hybrigenics has announced that all 60 patients were recruited under in just 6 weeks. The last treatment of the last patient is now scheduled for April 6, 2012 and the end of follow-up period of four weeks is scheduled for May 4, 2012. The full results of the study should be available earlier than planned initially, in June or July rather than fall 2012.
* On November 21, 2011, Hybrigenics has announced the start of Phase II clinical trial with oral inecalcitol in patients with moderate-to-severe psoriasis. Oral inecalcitol represents a potential alternative of choice in this therapeutic indication, more patient-friendly than injectable biologics against tumor-necrosis factor alpha (TNF-alpha) or interleukins and less toxic than oral cyclosporin, methotrexate or retinoids.
* On September 6, 2011, Hybrigenics has received the green light from Afssaps to conduct a phase II trial of inecalcitol in patients with moderate to severe psoriasis. The company has received a €650 000 loan from OSEO. This rate loan covers 45% of the whole cost of the trial. The study will be conducted by Pr Jean-Paul Ortonne (CHU Nice ). It could begin in Q4 2011 and should last a year.
