Clinical Trials

Date: 2016-09-29

Type of information: Interim results

phase: 2

Announcement: interim results

Company: Cempra (USA - NC)

Product: solithromycin

Action mechanism:

antibiotic. Solithromycin is a highly potent next-generation macrolide, the first fluoroketolide, which has potent activity against most macrolide-resistant bacterial strains. In vitro and in vivo studies have shown potent activity against S. pneumoniae as well as an extended spectrum of activity against CA-MRSA, streptococci, Haemophilus, enterococci, Mycobacterium avium and in animal models of malaria. It is also active against atypical bacteria, such as legionella, chlamydia, mycoplasma and ureaplasma, and against gonococci and other organisms that cause genitourinary tract infections. It is 8-16 times more potent than azithromycin and is active against azithromycin-resistant strains. Solithromycin's activity against resistant strains is driven by its ability to interact with three sites on the bacterial ribosome, compared to one for current macrolides. The binding to three ribosomal sites is expected to limit resistance development.

Disease: NASH (non-alcoholic steatohepatitis)

Therapeutic area: Hepatic diseases - Liver diseases

Country:

Trial details:

This Phase 2 open label study will enroll up to 15 patients with NASH without cirrhosis between 18 and 70 years of age. Patients on study will receive 400 mg (2x 200 mg capsules) of solithromycin once daily for 13 weeks. All patients will undergo a liver biopsy at baseline and upon completion of the study. The primary efficacy measure will be change in liver histology as measured by the NAFLD Activity Score (NAS). Fibrosis, ballooning degeneration, and markers of liver inflammation will also be evaluated, along with safety and tolerability. The trial is expected to complete patient enrollment by the end of 2016.

Latest news:

• On September 29, 2016, Cempra announced interim results showing anti- NASH effects in the first six nonalcoholic steatohepatitis ( NASH ) patients dosed with solithromycin in a Phase 2 study. Compared with baseline values, after 90 days of solithromycin treatment, all six NASH patients had a reduction in their nonalcoholic fatty liver disease (NAFLD) activity score (NAS) (mean reduction, 1.3) and their alanine aminotransferase (ALT) (mean reduction, 17.8 U/L).
Five of six patients had a reduction in their aspartate aminotransferase (AST), and the sixth patient had an AST that was unchanged and normal (mean reduction for the six patients, 10.1 U/L).
There were also mean reductions in ballooning hepatocyte degeneration and inflammation, both of which are histological signs of NASH . Solithromycin has been well tolerated in this study.
Based on the safety profile and activity seen in the first six patients, Cempra plans to continue the Phase 2 study to obtain data from up to 15 NASH patients. Enrollment is expected to complete in the first quarter of 2017.
• On January 5, 2016, Cempra announced first patient dosing in a Phase 2 clinical trial exploring the use of solithromycin in nonalcoholic steatohepatitis ( NASH ). Inflammation plays a key role in the progression of NASH , and the immunomodulatory and anti- NASH activity that has been observed with solithromycin in a murine diabetic NASH model may provide a treatment benefit to patients.