Date: 2014-11-05
Type of information: Results
phase: 1-2
Announcement: results
Company: BioLineRx (Israel)
Product: BL-7010
Action
mechanism: BL-7010 is a novel, non-absorbable, orally available polymer intended for the treatment of celiac disease. It has a high affinity for gliadins, the immunogenic proteins present in gluten that cause celiac disease. By sequestering gliadins, BL-7010 effectively masks them from enzymatic degradation and prevents the formation of immunogenic peptides that trigger the immune system. BL-7010 is excreted with gliadin from the digestive tract, preventing the absorption of gliadins\' peptides into the blood. This significantly reduces the immune response triggered by gluten. The safety and efficacy of BL-7010 were demonstrated in pre-clinical studies. BL-7010 was invented by Prof. Jean-Christophe Leroux from the Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, ETH Zurich, in Zurich, Switzerland and is being developed by BioLineRx under a worldwide exclusive license agreement with Univalor.
Disease: celiac disease
Therapeutic area: Autoimmune diseases - Inflammatory diseases
Country: Finland
Trial
details: The Phase 1/2 study is a two-part (single and repeated), double-blind, placebo-controlled, dose escalation study of BL-7010 in 32 patients at a world-leading site for celiac disease research in Finland. The primary objective of the study is to assess the safety of single and repeated ascending doses of BL-7010 in well-controlled celiac patients. Secondary objectives include an assessment of the systematic exposure, if any, of BL-7010 in the study patients. During the single-administration part of the study, several dose levels of BL-7010 were evaluated compared to placebo in a 6+2 standard design, with six patients receiving BL-7010 and two patients receiving placebo at each dose level. During the repeated-administration part of the study, several doses of either BL-7010 or placebo were tested for 14 days (three times per day) in the same 6+2 standard design. A total of 32 patients participated in the study, most of whom received more than one dose level of BL-7010 or placebo.
Professor Markku Maki, M.D., Ph.D., of the University of Tampere School of Medicine and the Tampere Center for Child Health Research in Finland, is the responsible coordinating investigator of the trial.
Latest
news: * On November 5, 2014, BioLineRx, a clinical-stage biopharmaceutical company dedicated to identifying, in-licensing and developing promising therapeutic candidates, announced successful final results from its Phase 1/2 study for BL-7010, a novel co-polymer for the treatment of celiac disease. BL-7010 was found to be safe and well tolerated in both single- and repeated-dose administrations, and the optimal safe dose for future development was determined. Over the next few months, the Company will conduct additional non-clinical studies and formulation development for BL-7010 in preparation for the upcoming randomized, placebo-controlled efficacy study, which BioLineRx expects to commence in the second half of 2015. In all single- and repeated-administration cohorts, pharmacokinetic analyses revealed no systemic exposure of BL-7010 in plasma and urine samples. Based on previous communications with a Notified Body in the European Union, the lack of systemic exposure will likely support a medical-device classification for BL-7010, which would significantly accelerate its development in Europe. Based on its strong safety and tolerability profile, BioLineRx has selected the one gram, three times per day regimen of BL-7010 as the optimal repeated dose for the upcoming efficacy study. Decreasing the dose to these levels substantially reduced the gastrointestinal (GI)-related adverse events (primarily diarrhea) observed previously at higher doses, while remaining within the anticipated therapeutic window for BL-7010 based on non-clinical studies. * On July 16, 2014, BioLineRx announced unblinded results from its Phase 1/2 study for BL-7010, a novel polymer for the treatment of celiac disease. The Phase 1/2 study, taking place at Tampere Hospital in Finland, is a two-part (single and repeated administration), double-blind, placebo-controlled, dose escalation study of BL-7010 in up to 32 well-controlled celiac patients. The primary objective of the study is to assess the safety of single and repeated ascending doses of BL-7010. Secondary objectives include an assessment of the systemic exposure, if any, of BL-7010. During the single-administration part of the study, six dose levels of BL-7010 were evaluated compared to placebo in a 6+2 standard design, with six patients on BL-7010 and two patients on placebo. This escalation stage reached the highest planned dose with no serious or dose-limiting adverse events. All planned doses were safe and well-tolerated with all patients completing this part of the study. During the second, repeated-administration part of the study, each patient received either 3 grams of BL-7010 or placebo for 14 days, three times per day, in the same 6+2 standard design. BL-7010 was well-tolerated over 14 days of treatment, with only one patient not completing the 14-day treatment period. Gastrointestinal-related adverse events (primarily diarrhea) were reported in six out of eight patients, though none were considered serious or dose-limiting and were also observed in one of the two patients on placebo. In light of these findings, and based on pre-clinical studies where the efficacious dose is predicted to be lower than the dose tested in the repeated administration stage of the study, the Company intends to further investigate lower repeated doses of BL-7010 in order to select the optimal dose for the upcoming efficacy study, which is expected to commence in early 2015. Importantly, pharmacokinetic analyses revealed no systemic exposure of BL-7010 in plasma and urine samples from all patients at all doses and time points tested, both in the single- and repeated-dose regimens. Based on previous communications with a Notified Body in the European Union, the lack of systemic exposure will likely support a medical-device classification in Europe for BL-7010. In the next few months BioLineRx will concentrate on selecting the optimal dose of BL-7010. The company plans to commence in Europe a randomized, placebo-controlled efficacy study in celiac patients early next year. * On March 10, 2014, BioLineRx has announced that BL-7010, has successfully completed the single administration, dose-escalation stage of the on-going Phase 1/2 clinical study. No serious adverse events were reported and there were no dose-limiting safety issues. Based on these positive safety and tolerability results, the Company will proceed with the repeated administration stage of the study. Results are expected in mid-2014. During the first part of the study, six dose levels of BL-7010 were evaluated compared to placebo. The escalation stage reached the highest planned dose, and although the study remains blinded at this point, no serious or dose-limiting adverse events were reported and all planned doses were found to be safe and well-tolerated. Consequently, all patients completed their participation in this part of the study. Based on these encouraging safety and tolerability results, the study will now progress to the repeated administration stage, in which each patient will receive either BL-7010 or placebo for 14 days, three times per day * On December 18, 2013, BioLineRx has announced enrollment of the first patient in a Phase 1/2 trial of BL-7010, for the treatment of celiac disease. The first patient was enrolled at Tampere Hospital in Finland, a world-leading site for celiac disease research. Results are expected in mid-2014. The company hopes to begin an efficacy study with BL-7010 in the second half of 2014. * On November, 4, 2013, BioLineRx has announced that it has received regulatory approval from the Finnish National Supervisory Authority for Welfare and Health (Valvira) to commence a Phase 1/2 safety trial for BL-7010, for the treatment of celiac disease. The study is expected to begin by the end of this year. * On September 24, 2013, BioLineRx, a biopharmaceutical development company, has announced that it has filed the necessary regulatory submissions to commence a Phase 1/2 trial for BL-7010 - for the treatment of celiac disease - with the Finnish National Supervisory Authority for Welfare and Health (Valvira). The relevant ethics committee has already approved commencement of the study. The CRO and data management vendors have already been selected for the study, which is expected to start in the fourth quarter of this year.
