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SteatohepatitisPhase 1NCT07052682

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

A Phase 1 study testing Ontamalimab in people with Steatohepatitis, run by Takeda at 15 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Steatohepatitis
What is being tested?
Ontamalimab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
15 sitesUnited States
Study dates
18 Jan 2023to 30 Dec 2024
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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).
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  • 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.
  • The participant has severe active inflammatory bowel disease (IBD). Participants with inactive IBD or active of mild to moderate severity that was documented either by prior endoscopy or in previous medical records for >6 months are permitted to enter if they do not require biological treatment or Janus kinase (JAK) inhibitors. Treatment with leukocyte apheresis or selective lymphocyte, monocyte, or granulocyte apheresis or plasma exchange 30 days before baseline (Day 1).
  • The participant has a severe immune-mediated inflammatory disease (IMID) (example, rheumatoid arthritis, spondylarthritis disease spectrum, connective tissue disorders, cutaneous inflammatory conditions such as psoriasis, atopic dermatitis, hidradenitis suppurativa, asthma, multiple sclerosis). Participants with inactive IMID or active IMID of mild to moderate severity are permitted to enter the study.
  • The participant has a change in body weight >=5% three months before start of the screening or after qualifying liver biopsy. If the participant had a liver biopsy within 24 weeks of screening but experienced a weight change of >=5% since the date of liver biopsy, the liver biopsy must be repeated at screening.
  • The participant has any laboratory abnormality or condition that, in the investigator's opinion, could adversely affect the safety of the participant or impair the assessment of study results.
  • The participant has known hypersensitivity to ontamalimab or formulation excipient.
  • The participant has active or latent infection with mycobacterium tuberculosis (TB) who have not completed a generally accepted full course of treatment before screening.
  • The participant has clinically significant abnormal chest X-ray findings at SV1 (or up to 12 weeks before the first screening visit if available), such as presence of active TB, general infections, heart failure, or malignancy.
  • The participant has a positive interferon-gamma release assay (IGRA) at screening or within 12 weeks before screening even in the absence of previously diagnosed active or latent TB. IGRA screening may be repeated during the screening period if the initial result is indeterminate. The participant may be enrolled if confirmatory IGRA results from the central laboratory are negative. If the confirmatory IGRA results from the central laboratory are positive, the participant should be screen-failed. If both initial and confirmatory IGRA results are indeterminate, the participant may be enrolled after a Mantoux tuberculin skin test is negative and after consultation with the sponsor and a pulmonary or infectious disease specialist who determines low risk of infection (example, the participant would be acceptable for immunosuppressant [example, anti-tumor necrosis factor (TNF) treatment] without additional action). If the time for consultation exceeds the visit window, the participant should be screen-failed and can be rescreened after the consultation establishes eligibility for study participation. This consultation must be included in the participant's medical history.
  • The participant has any unexplained symptoms suggestive of progressive multifocal leukoencephalopathy (PML) based on the targeted neurological assessment during the screening period.
  • The participant has HIV.
  • The participant has a medical condition (example, morbid obesity, claustrophobia) that prevent execution of protocol procedures including percutaneous liver biopsy, liver stiffness measurement (LSM) by FibroScan, and magnetic resonance imaging (MRI).
  • The participant is receiving treatment with vitamin E, thiazolidinediones, or glucagon-like peptide-1 receptor agonists (GLP-1 RA) unless on a stable dose for 3 months before qualifying liver biopsy and not initiated after qualifying liver biopsy and is anticipated to maintain the same dosing regimen throughout study participation.
  • The participant is using drugs, herbs, or supplements historically associated with causing or worsening nonalcoholic fatty liver disease (NAFLD)/NASH within 24 weeks before qualifying liver biopsy or any time after qualifying liver biopsy is performed, including the use of total parenteral nutrition.
  • The participant has a positive urine screen for amphetamines, cocaine, or opioids related to the use of these drugs at screening.
  • The participant is receiving methadone or buprenorphine unless on stable maintenance treatment for at least 6 months before screening. Participants with a positive urine drug screen due to prescription opioid-based medication are eligible if the prescription and diagnosis are reviewed and approved by the investigator.
  • The participant is using any prohibited concomitant medications as described in the protocol.
  • The participant has received a live (attenuated) vaccine within 4 weeks before baseline or is anticipated to receive a live vaccine during the study.
  • The participant has participated in another investigational study of a drug or device within 30 days before or within 5 half-lives of the prior investigational agent (whichever is longer) before baseline (Day 1).
  • The participant has participated in another investigational study targeting NASH, type 2 diabetes mellitus, or obesity within 6 months before baseline (Day 1).
  • The participant is concurrently participating in another therapeutic clinical study.
  • The participant has previously received ontamalimab.
  • The participant has had previous exposure to anti-integrin or anti-adhesion molecule treatment example, natalizumab, efalizumab, etrolizumab, vedolizumab, or any other investigational anti-integrin/adhesion molecule within 90 days before baseline (Day 1).
  • The participant has had previous exposure to any other biologic drugs with immunomodulatory properties such as anti-TNF, including biosimilars or anti-interleukin (IL)-12/23, or any nonbiologic treatment with immunomodulatory properties such as JAK inhibitors within 90 days or 5 half-lives (whichever is longer) before baseline (Day 1).
  • The participant is unavailable for follow-up assessment or investigator concern for participant's compliance with the protocol procedures.
  • The participant is a study site employee, an immediate family member (example, spouse, parent, child, sibling), or is in a dependent relationship with a study site employee who is involved in conduct of this study or may consent under duress.

Trial locations and contacts

15 sites in 1 country.

15 sites in 1 country

United States15 sites

  • Arizona Liver Health

    Chandler, Arizona, 85224

  • Southern California Research Center

    Coronado, California, 92118

  • The Liver Institute at Methodist Dallas Medical Center

    Dallas, Texas, 75203

  • Covenant Metabolic Specialist LLC

    Fort Myers, Florida, 33912

  • Houston Research Institute

    Houston, Texas, 77079

  • University of California, San Diego, NAFLD Research Center

    La Jolla, California, 92037

  • Tandem Clinical Research GI, LLC

    Marrero, Louisiana, 70072

  • Lucas Research, Inc

    Morehead City, North Carolina, 28557

  • California Liver Research Institute

    Pasadena, California, 91105

  • Inland Empire Clinical Trials, LLC

    Rialto, California, 92377

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

    Richmond, Virginia, 23298

  • Texas Liver Institute

    San Antonio, Texas, 78215

  • Pinnacle Clinical Research LLC

    San Antonio, Texas, 78229

  • Covenant Metabolic Specialist LLC

    Sarasota, Florida, 34240

  • Adobe Clinical Research, LLC

    Tucson, Arizona, 85712

Other trials in United States

About this study

Official title: A Multicenter, Single-arm, Open-label, Phase 1b Study to Explore the Mechanism of Action and Evaluate the Safety of Ontamalimab in Participants With Nonalcoholic Steatohepatitis With Fibrosis Stage 1 Through 4

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
Being tested
Ontamalimab
Keywords
Drug Therapy
Medical subject headings
Fatty Liver

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • OntamalimabDrug

    Also called SHP647, PF-00547659, TAK-647

    Ontamalimab SC injection.

Study groups in NCT07052682
Study groupRoleWhat they receive
OntamalimabExperimentalParticipants 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.
Receives: Drug: Ontamalimab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: From first dose of study drug up to Week 36

  2. 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.

    Measured: From first dose of study drug up to Week 36

  3. 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.

    Measured: From first dose of study drug up to Week 24

  4. 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.

    Measured: From first dose of study drug up to 36 weeks

  5. 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.

    Measured: From first dose of study drug up to Week 36

Secondary outcomes (3)

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

    Researchers measured the change in liver scarring using biomarkers. Biomarkers are substances measured in blood that show normal or abnormal activity taking place in the liver. Pro-C3 was measured in serum; Increasing levels indicate worsening of fibrosis activity. Blood samples were collected for assessment of Pro-C3 biomarker.

    Measured: Baseline up to Week 24

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

    Researchers measured the change in liver scarring using biomarkers. Biomarkers are substances measured in blood that show normal or abnormal activity taking place in the liver. Blood samples were collected for an assessment of ELF score. The ELF score was calculated from the concentrations of the following serum biomarkers: tissue inhibitor of metalloproteinases- 1 (TIMP-1), procollagen III n-terminal propeptide (PIIINP), and hyaluronic acid (HA). ELF was a score on a scale of severity assessment against biopsy-proven fibrosis. A score of less than (<) 7.7 is none to mild, greater than (>) 7.7-9.8 is moderate, >9.8 is severe. Higher ELF scores represented worse disease outcome.

    Measured: Baseline up to Week 24

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

    cT1 is a quantitative MRI relaxation parameter that measures liver inflammation and fibrosis. Participants underwent abdominal MRI to obtain liver cT1, which were used to assess fibro-inflammation. The change from baseline was calculated by subtracting the baseline values from the individual post-baseline values.

    Measured: Baseline, Week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Jul 2025
  2. Study start18 Jan 2023
  3. Primary completion30 Dec 2024
  4. Study completion30 Dec 2024

Why it stopped: Study was terminated early by the sponsor due to a strategic shift and reprioritization of clinical programs within Takeda.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07052682
Sponsor's protocol ID
TAK-647-1001
Status last verified
Aug 2025
First submitted
30 Jun 2025
Last updated
19 Aug 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: De-identified individual participant data from this particular study will not be shared as there is a reasonable likelihood that individual patients could be re-identified (due to the limited number of study participants/study sites, …)

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Ontamalimab in people with Steatohepatitis, run by Takeda at 15 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 50 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 19 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Aug 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Treatment-emergent Adverse Events (TEAEs) (time frame: From first dose of study drug up to Week 36). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07052682.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2025.

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