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

NCT07052682 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: TAK-647-1001
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 15

Brief Summary

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.

Conditions

Steatohepatitis

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (5)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs)

  An Adverse Event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. TEAEs was defined as any event that emerged or manifested at or after the initiation of treatment with a study drug or medicinal product, or any existing event that worsened in either intensity or frequency following exposure to the study drug or medicinal product.

  From first dose of study drug up to Week 36

• Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Values

  Laboratory parameters included serum chemistry, hematology, urinalysis, and coagulation. Any Abnormality in clinical laboratory results which are deemed clinically significant by the investigator were reported.

  From first dose of study drug up to Week 36

• Number of Participants With Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECGs) Findings

  ECG included heart rate, QRS intervals, QT intervals, PR intervals, RR intervals and QT intervals corrected for heart rate using Fridericia's formula (QTcF) intervals parameters measurement. Any abnormality in ECG assessments which were deemed clinically significant by the investigator were reported.

  From first dose of study drug up to Week 24

• Number of Participants With Clinically Significant Abnormalities in Vital Signs

  Vital signs included measurement of pulse rate, systolic, diastolic blood pressure, respiratory rate, Body mass index (BMI), body temperature and height. Any abnormality in vital signs which are deemed clinically significant by the investigator were reported.

  From first dose of study drug up to 36 weeks

• Number of Participants With Clinically Significant Abnormalities in Body Weight

  Body weight was measured in kilograms (kg) at the specified time points. Any abnormality in body weight which are deemed clinically significant by the investigator were reported.

  From first dose of study drug up to Week 36

Secondary Outcomes (3)

• Percent Change From Baseline in Pro-Collagen Type III (Pro-C3) Through Week 24

  Baseline up to Week 24

• Percent Change From Baseline in Enhanced Liver Fibrosis (ELF) Through Week 24

  Baseline up to Week 24

• Change From Baseline in Liver Iron-corrected T1 Mapping by Magnetic Resonance Imaging (cT1 MRI) at Week 24

  Baseline, Week 24

Study Arms (1)

Ontamalimab

EXPERIMENTAL

Participants receive ontamalimab 75 milligrams (mg) subcutaneous (SC) injection using a prefilled syringe once every 4 weeks (Q4W) on Day 1 and the last dose is administered at Week 20 with a total treatment period of 24 weeks.

Drug: Ontamalimab

Interventions

Ontamalimab DRUG

Ontamalimab SC injection.

Also known as: SHP647, PF-00547659, TAK-647

Ontamalimab

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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:

• Aspartate aminotransferase (AST) levels greater than (\>) 5\*the upper limit of normal (ULN).
• Alanine aminotransferase (ALT) levels \>5\*ULN.
• 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.
• 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.

Sponsors & Collaborators

• Takeda: lead

Study Sites (15)

Arizona Liver Health

Chandler, Arizona, 85224, United States

Location

Adobe Clinical Research, LLC

Tucson, Arizona, 85712, United States

Location

Southern California Research Center

Coronado, California, 92118, United States

Location

University of California, San Diego, NAFLD Research Center

La Jolla, California, 92037, United States

Location

California Liver Research Institute

Pasadena, California, 91105, United States

Location

Inland Empire Clinical Trials, LLC

Rialto, California, 92377, United States

Location

Covenant Metabolic Specialist LLC

Fort Myers, Florida, 33912, United States

Location

Covenant Metabolic Specialist LLC

Sarasota, Florida, 34240, United States

Location

Tandem Clinical Research GI, LLC

Marrero, Louisiana, 70072, United States

Location

Lucas Research, Inc

Morehead City, North Carolina, 28557, United States

Location

The Liver Institute at Methodist Dallas Medical Center

Dallas, Texas, 75203, United States

Location

Houston Research Institute

Houston, Texas, 77079, United States

Location

Texas Liver Institute

San Antonio, Texas, 78215, United States

Location

Pinnacle Clinical Research LLC

San Antonio, Texas, 78229, United States

Location

VCU Dept of Internal Medicine, Division of GI, Hepatology & Nutrition

Richmond, Virginia, 23298, United States

Location

Related Links

• Click here for more information about this trial in easy-to-understand language, including a Plain Language Summary of the results if the trial has been completed.

MeSH Terms

Conditions

Fatty Liver

Interventions

ontamalimab

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases

Limitations and Caveats

The study was terminated early by the sponsor due to a strategic shift and reprioritization of clinical programs within Takeda.

Results Point of Contact

• Title: Study Director
• Organization: Takeda

TrialDisclosures@takeda.com

+1-877-825-3327

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2025
• First Posted: July 6, 2025
• Study Start: January 18, 2023
• Primary Completion: December 30, 2024
• Study Completion: December 30, 2024
• Last Updated: August 19, 2025
• Results First Posted: August 19, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (15)