A Study to Evaluate How Ontamalimab Works and Assess Its Safety and Tolerability in People With Nonalcoholic Steatohepatitis With Fibrosis Stages 1 to 4

Stopped early · Phase 1

Conditions studied: Steatohepatitis

In brief

The main aim of this study is to evaluate the safety and tolerability of ontamalimab in participants with a liver disease called nonalcoholic steatohepatitis (NASH) or metabolic dysfunction-associated steatohepatitis (MASH) with scarring in the liver (fibrosis stage 1 to 4). The study will also check if there are any important changes in the body's health markers (biomarkers) from the beginning of the study to see if ontamalimab stops liver scarring and reduces inflammation of the liver. Participants will be in the study for approximately up to 46 weeks.

Key facts

Study ID

NCT07052682

Run by

Takeda

People needed

11

Starts

2023-01-18

Expected to finish

2024-12-30

Last updated by the study team

2025-08-19

Who can join

Age: 18 and older, up to 70. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• The participant is willing and able to understand and fully comply with study procedures and requirements, in the opinion of the investigator.
• The participant and/or the participant's legally acceptable representative has provided informed consent (that is, in writing, documented via a signed and dated informed consent form [ICF] or electronic consent [eConsent] if applicable) and any required privacy authorization prior to the initiation of any study procedures.
• The participant is aged 18 to 70 years, inclusive, at the time of signing the ICF.
• The participant has signs of fibrogenic activity (Pro-C3 greater than or equal to [>=] 12.6 nanograms per milliliter [ng/mL], ELF score >=7.7) at the Week -8 (screening visit 1 [SV1]) (applies to all participants regardless of whether historical biopsy results are available at screening).
• The participant has indication of NASH via biopsy (Nonalcoholic fatty liver disease activity score [NAS] >=3 with at least 1 point in lobular inflammation) and liver fibrosis stage 1 (F1) through fibrosis stage 4 compensated cirrhotic (F4cc) according to NASH Clinical Research Network (CRN).
• The participant is a male participant or a nonpregnant, nonlactating female participant who, if sexually active, agrees to comply with the contraceptive requirements of the protocol, or a female participant of nonchildbearing potential. Participants of reproductive potential who are sexually active must agree to use appropriate contraception (that is, highly effective methods for female participants and medically appropriate methods for male participants) for the duration of the study and for at least 12 weeks after the last dose of study drug.
• The participant, if capable of breastfeeding, agrees to forego breastfeeding for the period from informed consent until 12 weeks after the last dose of study drug.

You may not qualify if…

• The following laboratory findings are exclusionary for all participants if found during screening visits (Week -8 [SV1], Week -6 [SV2] or at Day -4 visit [Visit 4a2]):
• Aspartate aminotransferase (AST) levels greater than (>) 5*the upper limit of normal (ULN).
• Alanine aminotransferase (ALT) levels >5*ULN.
• The following laboratory findings are exclusionary for all participants if found during either screening visit (SV1 or SV2):
• Alkaline phosphatase (ALP) >=2*ULN.
• Serum creatinine >=1.5*ULN or has an estimated glomerular filtration rate (eGFR) less than (<) 45 milliliters per minute per 1.73 square meters (mL/min/1.73 m\^2).
• International normalized ratio (INR) >=1.3 (except for participants who are receiving anticoagulant treatment).
• Total bilirubin level (TBL) >=ULN (except for participants with a documented history of Gilbert's syndrome if direct bilirubin is within normal reference range).
• Direct bilirubin >=3*ULN.
• Platelet count <60*10\^9 per liter (/L).
• The participant has been diagnosed with decompensated liver disease, or has new signs of decompensation and/or clinically meaningful change in disease status based on the judgment of the investigator (including but not limited to clinically significant changes in TBL, albumin, INR, creatinine, and/or AST and ALT levels) are observed during the screening period, or has any of the following during screening period:
• Presence or history of ascites, hepatic encephalopathy, or variceal bleeding.
• Presence or history of Child-Pugh >6 (Class B or C), unless due to therapeutic anticoagulation.
• Presence or history of model for end-stage liver disease (MELD) score >12. Note: It is the investigator's decision, in consultation with the sponsor, to allow participants to enter the study who have clinically meaningful rising tendencies in liver chemistries or significantly elevated liver chemistries that do not yet satisfy Exclusion Criterion #1 but could be interpreted as clinically concerning (that is, AST or ALT >4*ULN) at any visit during the screening period.
• The participant has other diagnosed causes of liver disease based on medical history and/or baseline evaluation of laboratory and/or histology results, including, but not limited to viral (example, chronic hepatitis B, hepatitis B virus surface antigen [HBsAg] positive, or hepatitis B core antibody [HBcAB] positive; or chronic hepatitis C or hepatitis C virus antibody [HCVAb] positive and hepatitis C [HCV] ribonucleic acid [RNA] positive; or human immunodeficiency virus [HIV]-antibody positive), alcoholic (alcohol consumption greater than 4 units on any day or 14 units per week for male participants, or greater than 3 units on any day or 7 units per week for female participants [1 unit of alcohol is present in one 12 ounces [oz]/355 milliliters [mL] beer (approximately 5 percentage [%] alcohol), one 5 oz/148 mL glass of wine (approximately 12% alcohol), and one 1.5 oz/44 mL measure of 80-proof liquor (approximately 40% alcohol)]), or autoimmune conditions (example, primary sclerosing cholangitis, primary biliary cirrhosis, autoimmune hepatitis, drug-induced hepatotoxicity), and other rare liver disease (example, alpha-1-antitrypsin deficiency, Wilson disease, hemochromatosis). Note: If a participant tests negative for HBsAg but positive for HBcAb, the participant would be considered eligible if no presence of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) is confirmed by HBV DNA polymerase chain reaction (PCR) reflex testing performed by the central laboratory. Participants who are HCVAb positive without evidence of HCV RNA may be considered eligible (spontaneous viral clearance or previously treated and cured [defined as no evidence of HCV RNA at least 12 weeks before baseline]).
• The participant has a history of impaired hemostasis that, in the investigator's judgement, would increase the risk to the participant if he or she participates in the study.
• The participant has a significant concurrent medical condition at the time of screening or baseline, including, but not limited to, the following:
• Any major illness/condition or evidence of an unstable clinical condition (example, hepatic, renal, hematologic, gastrointestinal, endocrine [example, uncontrolled diabetes or type 1 diabetes mellitus, or thyroid disease], neurological [pre-existing demyelinating disorder such as multiple sclerosis or new onset seizures, unexplained sensory motor, or cognitive behavioral, neurological deficits, or significant abnormalities noted during screening], cardiovascular, pulmonary, immunologic [example, Felty's syndrome], or local active infection/infectious illness [any bacterial, fungal, or viral, example, clinically active cytomegalovirus, Epstein-Barr virus, herpes simplex virus]) that, in the investigator's judgment will substantially increase the risk to the participant if he or she participates in the study.
• Note: Participants with hemoglobin A1c (HbA1c) of >=6.5% at screening (SV1; Week -8) without a previous diagnosis of type 2 diabetes mellitus (T2DM) should be excluded from the study. Participants with a previous diagnosis for T2DM are permitted to enter the study if on a stable regimen of antidiabetic therapy for at least 90 days before screening. Participants who are on a stable regimen of antidiabetic therapy for at least 90 days before screening (SV1; Week -8) and have HbA1c of >=9% at Week -8 (SV1) should be excluded.
• Presence of acute coronary syndrome (example, acute myocardial infarction, unstable angina pectoris) within 24 weeks before screening.
• History of significant cerebrovascular disease within 24 weeks before screening.
• Cancer or history of cancer, including hepatocellular carcinoma or cholangiocarcinoma, or lymphoproliferative disease within the previous 5 years (other than resected cutaneous basal cell carcinoma, squamous cell carcinoma, or carcinoma in situ of the uterine cervix that has been treated with no evidence of recurrence).
• Any other severe acute or chronic medical or psychiatric condition or laboratory or ECG abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.
• Transplanted organ or history of liver transplantation.
• Significant trauma or major surgery within 4 weeks before the first screening visit, or with any major elective surgery planned to occur during the study.

Where it is running

• Arizona Liver Health — Chandler, Arizona, United States
• Adobe Clinical Research, LLC — Tucson, Arizona, United States
• Southern California Research Center — Coronado, California, United States
• University of California, San Diego, NAFLD Research Center — La Jolla, California, United States
• California Liver Research Institute — Pasadena, California, United States
• Inland Empire Clinical Trials, LLC — Rialto, California, United States
• Covenant Metabolic Specialist LLC — Fort Myers, Florida, United States
• Covenant Metabolic Specialist LLC — Sarasota, Florida, United States
• Tandem Clinical Research GI, LLC — Marrero, Louisiana, United States
• Lucas Research, Inc — Morehead City, North Carolina, United States
• The Liver Institute at Methodist Dallas Medical Center — Dallas, Texas, United States
• Houston Research Institute — Houston, Texas, United States
• Texas Liver Institute — San Antonio, Texas, United States
• Pinnacle Clinical Research LLC — San Antonio, Texas, United States
• VCU Dept of Internal Medicine, Division of GI, Hepatology & Nutrition — Richmond, Virginia, United States

Full record on ClinicalTrials.gov

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