Genoma Research Group, Inc. | Miami, FL
Status and phase
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About
This seamless, adaptive, two-stage, Phase 2b/3, randomized, double-blind, multicenter, parallel-groups, placebo-controlled study will assess the efficacy, safety, and tolerability of belapectin compared with placebo in patients with nonalcoholic steatohepatitis (NASH) cirrhosis and clinical signs of portal hypertension but without esophageal varices at baseline.
Enrollment
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Volunteers
Inclusion criteria
Each subject must meet all of the following criteria to be enrolled in this study:
Is male or female, ≥ 18 and ≤ 75 years of age at the time of Screening.
Is willing and able to provide written informed consent prior to the initiation of any study-specific procedures.
Has evidence of portal hypertension, with either one of the following:
platelet count <150,000/mm3
OR
documented hepatic venous pressure gradient (HVPG) measurement >6 mmHg
OR
at least two of the following:
Has a history confirming nonalcoholic steatohepatitis (NASH) cirrhosis, with at least one of the following:
Note: All liver biopsy blocks and/or slides for eligibility assessments (including those from historical biopsies) will be reviewed by the central study pathologist while the subject is in Screening. Results from the central study pathologist must be available before the subject is randomized.
Absence of hepatocellular carcinoma (HCC) by valid imaging (eg, ultrasound, CT scan, or MRI) within 6 months prior to randomization. If no such imaging result is available, then ultrasound imaging should be performed as part of standard of care.
Patients with diabetes mellitus can be enrolled, if they are adequately controlled on a stable dose or doses of antidiabetic medication(s) for at least 3 months before Screening, and their screening HbA1c is ≤9.5%.
Patients on vitamin E or pioglitazone can be enrolled if they are on a stable dose and regimen for at least 3 months before screening, and the dose is expected to be held constant during the trial.
Patients on a statin can be enrolled if they are on a stable regimen for at least 3 months before Screening, and expected to be held stable during the trial.
Is not pregnant and must have a negative serum pregnancy test result prior to randomization.
Is of non-childbearing potential or if a fertile man or woman participating in heterosexual relations, agrees to use two acceptable means of contraception (ie, 2 effective methods of contraception, one of which must be a physical barrier method [eg, male or female condom, diaphragm] when combined with a highly effective method of contraception [ie, a method with a failure rate of <1% per year when used consistently and correctly]) throughout his/her participation in this study and for 90 days after discontinuation of study treatment.
Highly effective forms of contraception include:
Surgically sterile males and females are not required to use contraception provided they have been considered surgically sterile for at least 6 months. Surgical sterility includes history of surgically successful vasectomy, hysterectomy, or bilateral salpingo-oophorectomy. Postmenopausal women who have been amenorrheic for at least 2 years at the time of Screening will be considered sterile.
If a lactating woman, agrees to discontinue nursing before the start of study treatment and refrain from nursing until 90 days after the last dose of study treatment.
If a man, agrees to refrain from sperm donation throughout the study period and for a period of 90 days following the last dose of investigational medicinal product (IMP). Female subjects may not begin a cycle of ova donation or harvest throughout the study period and for a period of 90 days following the last dose of IMP.
Exclusion criteria
Subjects meeting any of the following criteria will be excluded from the study:
Presence of esophageal, gastroesophageal, or isolated gastric varices, based on an upper gastrointestinal (GI) esophagogastroduodenoscopy (EGD) exam conducted during Screening. Patients with portal hypertensive gastropathy could be enrolled.
History of hepatic cirrhosis decompensation including any episode of variceal bleeding, ascites not controlled by medication, spontaneous bacterial peritonitis or overt hepatic encephalopathy (West Haven grade ≥2 as assessed by the principal investigator), OR develops signs of hepatic cirrhosis decompensation during Screening.
Known or suspected abuse of alcohol (>20 g/day for women or >30 g/day for men [on average per day]), as per medical history. Significant alcohol consumption is defined as more than 20 grams per day in females and more than 30 grams per day in males. On average, a standard drink in the United States is considered to be 14 grams of alcohol, equivalent to 12 fluid ounces of regular beer (5% alcohol), 5 fluid ounces of table wine (12% alcohol), or 1.5 fluid ounces of 80 proof spirits (40% alcohol).
Alcohol dependence (ie, a score >8 on the Alcohol Use Disorders Identification Test)
Narcotics or any other drug abuse or dependence in the last 5 years
Prior trans-jugular intrahepatic portal-systemic (TIPS) shunt procedure
Documented causes of liver disease other than NASH, including but not restricted to:
Viral hepatitis, unless eradicated at least 3 years prior to Screening
Documented drug-induced liver disease
Alcoholic liver disease
Autoimmune hepatitis
Wilson's disease
Hemochromatosis
Primary biliary cholangitis
Primary sclerosing cholangitis
Genetic hemochromatosis
History or planned liver transplantation
Alpha-1 antitrypsin deficiency
History of human immunodeficiency virus (HIV), or positive HIV test at Screening
Any of the following test or score:
serum alanine aminotransferase (ALT) > 5 × upper limit of normal (ULN)*
serum aspartate aminotransferase (AST) > 5 × ULN*
*Screening values will be obtained at Screening Visit 1 (SV1) and Screening Visit 2(SV2) (which will be separated by 2 to 4 weeks). A second screening value that is >50% higher than the first value should prompt re-evaluation of the severity of the underlying liver disease and eligibility for this trial. If a transaminase level at SV2 is >33% different from the level at SV1, then additional measurements should be performed at Screening Visit 3 (SV3). In such cases, the baseline transaminase levels will be established for subjects using the mean value of 4 evaluations [ie, at SV1, SV2, SV3, and Baseline (ie, pre-dose during Visit 1)].
serum alkaline phosphatase (ALP) > 2 × ULN
mean platelet count < 50,000/mm3
total bilirubin ≥ 2.0 mg/dL (subjects with a documented history of Gilbert's syndrome can be enrolled if the direct bilirubin is within normal reference range)
model for end-stage liver disease (MELD) score ≥12
Child-Turcotte-Pugh (CTP) Score ≥7 Note: Following Phase 2b, subjects with CTP scores ≥7 may be enrolled if recommended* by the Data Safety Monitoring Board (DSMB) and approved by the Trial Steering Committee (TSC), based on the planned interim analysis (IA). [*based on DSMB review of preliminary results from a separate hepatic impairment clinical trial (Study GT-032) which is assessing belapectin safety and pharmacokinetic (PK) in cirrhotic subjects with CTP scores ≥7.
estimated glomerular filtration rate < 45 mL/min* *Note: per Modification of Diet in Renal Disease algorithm
Taking an angiotensin converting enzyme inhibitor, angiotensin II receptor blocker, or β-1 selective adrenergic receptor inhibitor, unless on a stable regimen for at least 3 months prior to Screening and no changes in the regimen are anticipated during the study. Subjects taking a non-selective beta blocker are not eligible to be enrolled (Investigators are encouraged to substitute another medication, if clinically warranted).
History of major surgery during Screening.
History of a solid organ transplant requiring immunosuppressive therapy.
History of bariatric surgery within 1 year of randomization, or plan to undergo bariatric surgery during the study.
Has positive screening test for illicit drugs of abuse at Screening.
Has participated in an investigational new drug study within 30 days or 5 half-lives whichever is longer, prior to randomization.
Has a history of malignancy within 5 years of randomization, except for basal cell carcinoma, squamous cell carcinoma, and adequately treated in situ uterine cervical cancer.
Has clinically significant cardiovascular disease (eg, uncontrolled hypertension, myocardial infarction, unstable angina), New York Heart Association Grade II or greater congestive heart failure, serious cardiac arrhythmia requiring intervention (eg, pacemaker/ablation) or Grade II or greater peripheral vascular disease.
Has a history of clinically significant hematologic, renal, hepatic, pulmonary, neurological, psychiatric, gastrointestinal, systemic inflammatory, metabolic or endocrine disorder or any other condition that, in the opinion of the Investigator, renders the subject a poor candidate for inclusion into the study.
Has known allergies to the IMP or any of its excipients.
Has previously received belapectin within 6 months of randomization.
Is an employee or family member of the Investigator or study center personnel.
Primary purpose
Allocation
Interventional model
Masking
357 participants in 3 patient groups, including a placebo group
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Data sourced from clinicaltrials.gov
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