Clinical Trials

Date: 2017-05-18

Type of information: Initiation of development program

phase: 3

Announcement:

Company: Albireo Pharma (USA - MA)

Product: A4250 ((2S)-2-{[(2R)-2-[({[3,3-dibutyl-7-(methylthio)-1,1-dioxido-5-phenyl-2,3,4,5-tetrahydro- 1,2,5-benzothiadiazepin-8-yl]oxy}acetyl)amino]-2-(4-hydroxyphenyl)acetyl]amino}butanoic acid)

Action mechanism: ileal bile acid transporter (IBAT) inhibitor. The product belongs to a class of inhibitors of the ileal bile acid transporter. Usually bile excreted into the small bowel is being reused by a transport mechanism in which bile acids are absorbed in the distal part of the small bowel. A4250 decreases this re-absorption and will reduce the toxic levels of bile acids in the diseases described above. By using a specialized delivery technology, the bile acids will be neutralized in the large bowel.

Disease: progressive familial intrahepatic cholestasis (PFIC)

Therapeutic area: Rare diseases - Genetic diseases - Liver diseases - Hepatic diseases

Country:

Trial details: Albireo's planned Phase 3 PFIC program includes a single randomized, double blind, placebo controlled, multicenter clinical trial and an open label long-term extension study. The double blind trial is designed to enroll 60 patients with PFIC (subtypes 1 or 2), ages six months to 18 years, at sites in the United States , Canada , western Europe , the Middle East and Australia . Patients will be assigned to receive either 40 µg/kg/day or 120 µg/kg/day of A4250, or placebo, for six months. Patients taking a stable dose of medication to manage pruritus when entering the trial will be permitted to continue such background medication during the trial, subject to specified exceptions. The trial will have a primary endpoint for U.S. purposes, a different primary endpoint for E.U. purposes, and several secondary endpoints, including progression to surgery, change in growth markers and liver biochemistry variables, and others. The primary endpoint for FDA evaluation, and a key secondary endpoint for EMA evaluation, will be an assessment of change in pruritus using a proprietary tool developed by Albireo. The trial's primary endpoint for EMA evaluation, and a key secondary endpoint for FDA evaluation, will be sBA responder rate, with a responder being a patient who achieves a predetermined reduction in sBA levels. Albireo intends to power the trial to demonstrate a statistically significant difference between A4250 and placebo on each of the regional primary endpoints based on a significance level of 5% (p ? 0.05, two sided). Patients in the trial will have the opportunity to participate in the open label extension study to assess long-term safety and durability of response.

Latest news:

• • On May 18, 2017, Albireo Pharma announced key study design details for its planned Phase 3 program of lead product candidate, A4250, in patients with progressive familial intrahepatic cholestasis (PFIC) determined following consultations with the FDA and European Medicines Agency (EMA). The planned Phase 3 PFIC program includes a single randomized, double blind, placebo controlled, multicenter, six-month treatment clinical trial designed to enroll 60 patients and an open label long-term extension study. The primary endpoint for FDA evaluation, and a key secondary endpoint for EMA evaluation, will be an assessment of change in pruritus. The primary endpoint for EMA evaluation, and a key secondary endpoint for FDA evaluation, will be serum bile acid (sBA) responder rate. Elevated sBA levels are associated with the pathogenesis of PFIC, and pruritus is a common and debilitating symptom of the disease.
• The trial will also have several additional secondary endpoints. Patients in the trial will have the opportunity to participate in the open label extension study to assess long-term safety and durability of response. The planned double blind Phase 3 trial, together with available data from the then-ongoing extension study, are expected to form the primary support for drug approval applications for A4250 in both the United States and European Union for the treatment of patients with PFIC. In a recently completed open label Phase 2 clinical trial in children with cholestatic liver diseases, most patients showed both an improvement in pruritus across multiple scales and a reduction in serum bile acid levels after four weeks of treatment with A4250. There were no serious adverse events determined to be treatment-related observed in the trial, and most adverse events, including some increased transaminases, were mild, transient and assessed as not treatment related. A4250 exhibited a favorable overall tolerability profile in the trial. In parallel with the planned Phase 3 program, Albireo is supporting an independent research study that is pooling and analyzing long-term PFIC patient data from a number of academic centers to support the clinical utility of the reduction of sBAs in the treatment of PFIC. Albireo plans to submit the findings from the study when available to both the FDA and EMA in support of its anticipated drug approval applications for A4250.

Is general: Yes