Health Boards
Hybrigenics bio-pharmaceutical company, with a focus on research and development of new treatments against proliferative diseases, announces 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.
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-γ) and tumor necrosis factor alpha (TNF-α) 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.
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.
“Two-thirds of inecalcitol-treated psoriasis patients showed some degree of response (PASI 50) but only one fourth had a clinically-relevant improvement (PASI 75) at week 12 or at week 16. A hypothesis could be that a longer duration of treatment might be necessary for inecalcitol to fully improve all the responders”, commented Dr Jean- François Dufour-Lamartinie, Hybrigenics’ Head of clinical R&D. He added: “the confirmation of inhibition of normal PTH secretion by inecalcitol, a fast, strong and straightforward effect observed in all treated patients, without any placebo effect, deserves further clinical investigation in chronic kidney disease patients who suffer from pathologically elevated PTH levels”.
Source: hybrigenics.com
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-γ) and tumor necrosis factor alpha (TNF-α) 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.
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.
“Two-thirds of inecalcitol-treated psoriasis patients showed some degree of response (PASI 50) but only one fourth had a clinically-relevant improvement (PASI 75) at week 12 or at week 16. A hypothesis could be that a longer duration of treatment might be necessary for inecalcitol to fully improve all the responders”, commented Dr Jean- François Dufour-Lamartinie, Hybrigenics’ Head of clinical R&D. He added: “the confirmation of inhibition of normal PTH secretion by inecalcitol, a fast, strong and straightforward effect observed in all treated patients, without any placebo effect, deserves further clinical investigation in chronic kidney disease patients who suffer from pathologically elevated PTH levels”.
Source: hybrigenics.com