NORCROSS, Ga.—Galectin Therapeutics Inc. reported today that the company has enrolled its first patients in the NASH-RX trial for belapectin in in nonalcoholic steatohepatitis (NASH) cirrhosis patients who have clinical signs of portal hypertension, and who are at risk of developing esophageal varices.
NASH-RX is an adaptively-designed Phase 2b/3 trial of its galectin-3 inhibitor belapectin (GR-MD-02), Galectin’s lead compound. Galectin-3 plays a major role in diseases that involve scarring of organs, including fibrotic disorders of the liver, lung, kidney, heart and vascular system. The drug binds to galectin proteins and disrupts their function.
Preclinical data in animals have shown that belapectin has robust treatment effects in reversing liver fibrosis and cirrhosis. Belapectin has also previously shown that it can prevent the development of new varices in this patient population in the Phase 2 NASH-CX clinical trial.
NASH-RX is expected to enroll approximately 315 NASH patients in the Phase 2b part of the trial at approximately 130 sites in 12 countries in North America, Europe, Asia and Australia. During the Phase 2b part of the trial, two belapectin doses, 2 mg/kg of lean body mass (LBM) and 4 mg/kg LBM, will be compared to placebo. Prior trials have demonstrated the good tolerance profile and apparent safety of belapectin with doses of up to 8 mg/kg LBM, notably for up to 52 weeks of treatment in patients with NASH cirrhosis in the Phase 2b NASH-CX study.
The study design provides for a pre-specified interim analysis (IA) of efficacy and safety data conducted after all planned subjects in the Phase 2b component have completed at least 78 weeks (18 months) of treatment and a gastro-esophageal endoscopic assessment. This adaptive design allows for patients to seamlessly transition from the Phase 2b component into the Phase 3 stage, as well as helping to determine the optimal dose, bolstering the efficacy signal, and re-evaluating the sample size and statistical power for the Phase 3 stage of the trial.
These adaptations are designed to increase the statistical power for detecting a successful outcome. The IA also provides for adjustment in the randomization ratio, refinement of inclusion/exclusion criteria and the potential termination of the study for either overwhelming efficacy or futility.
“The unmet medical need for an effective treatment for patients with NASH cirrhosis remains a compelling motivation to vigorously pursue our therapy. Moreover, if the results of the NASH-RX trial are compelling, there could be the potential for accelerated FDA approval and/or partnership opportunities,” stated Harold H. Shlevin, Ph.D., president and chief executive officer of Galectin Therapeutics.
Unlike clinical trials focused primarily on earlier stages of NASH, the NASH-RX study population will comprise patients with compensated liver cirrhosis. Based on the results of the NASH-CX trial, NASH-RX is focused on patients who have not yet developed esophageal varices but are at increased risk of developing these potentially life-threatening complications. Patient selection for both Phase 2b and Phase 3 will be based on clinical signs of portal hypertension such as thrombocytopenia, splenomegaly and/or evidence of collateral vessels.
The primary endpoint of the trial is to assess the effect of belapectin on the incidence of new varices. A centralized review system of video recording of esophagogastroduodenoscopy (EGD) has been put in place, and the primary endpoint will be adjudicated by expert EGD readers. Key secondary endpoints will assess the type of varices (sizes and/or bleeding), and other clinical events such as ascites, hepatic encephalopathy, listing for liver transplantation or death.
“Once liver fibrosis has progressed to cirrhosis, NASH patients can no longer expect significant improvements from changes in their lifestyle. These patients are in dire need of new options, and this trial may prove pivotal in improving their condition,” added Pol Boudes, M.D., chief medical officer for Galectin. “The study’s seamless and adaptive design is very innovative, and the primary endpoint minimizes the inconvenience for patients while being relevant to real life medical practice. We are extremely excited to start the study and give thanks in advance to all the patients who will participate and the medical teams that will support them.”