A Phase 2 interventional study of Emapalumab in Hepatitis, sponsored by Children's Healthcare of Atlanta. Not yet recruiting at 1 site in United States. Open to participants aged 1 Year to 30 Years. Per ClinicalTrials.gov, last updated 2026-08-04.
Sponsored by Children's Healthcare of Atlanta · Phase 2, Interventional, and Treatment
The goal of this study is to see whether a medicine called emapalumab, a monoclonal antibody, is safe and works well for patients aged 1 year and older who have indeterminate severe hepatitis with T-cell activation and have not responded well to steroids or still need them.
This study has a Screening Cohort and an Intervention Cohort.
The Screening Cohort will enroll patients with severe hepatitis of all etiologies to observe and collect research samples. Patients enrolled on the Screening Cohort will be asked to participate on the Intervention Cohort if they develop steroid-refractory/ dependent indeterminate severe hepatitis (iSH-T). Additionally, patients may bypass the Screening Cohort and enroll directly in the Intervention Cohort if they already meet its eligibility criteria. Patients in the Intervention Cohort will be treated with emapalumab.
This clinical protocol evaluates the use of emapalumab, an anti-IFN-γ monoclonal antibody, in children aged ≥1 year with steroid-refractory or steroid-dependent indeterminate severe hepatitis with T cell activation (iSH-T). This study aims to establish a safe and effective treatment pathway for a previously steroid-refractory/dependent subjects with iSH-T.
Pediatric severe acute hepatitis is a rare but serious disorder that can rapidly progress to liver failure. Previously healthy children who develop severe acute hepatitis can unpredictably progress to pediatric acute liver failure (PALF) over the course of days to weeks. Importantly, as many as 30-50% of all PALF cases have no specific causal etiology for their liver failure and are termed indeterminate PALF (iPALF) and are at the highest risk for liver transplantation. Work from the PALF study group investigators has identified that iPALF is a leading indication for liver transplantation in children. Additional investigation indicates that iPALF patients have significant T cell activation and CD8+ T cell infiltration of their hepatic tissue. There are reports using immunosuppression in iPALF and PALF with favorable results and it is also the subject of a current multicenter trial in children (NCT04862221).
343 studies on the registry are indexed under Hepatitis; 51 are open to participants now.
This study's planned enrollment of 28 is below the median of 85 across 245 interventional studies indexed under Hepatitis.
Browse Hepatitis studies →Children's Healthcare of Atlanta is the lead sponsor of 97 studies on the registry; 6 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria (Screening Cohort):
Inclusion Criteria (Intervention Cohort; patients who meet Intervention Cohort eligibility can bypass Screening Cohort enrollment):
Evidence of T-cell activation at initial diagnosis, as indicated by one of the following:
Exclusion Criteria (Intervention Cohort; patients who meet Intervention Cohort eligibility can bypass Screening Cohort enrollment):
Organ dysfunction assessment defined below:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
INR, PT and aPTT (clotting tests)
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Reproductive potential
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Live vaccines
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants on the Intervention Cohort will receive a combination of immunomodulatory regimen using emapalumab and methylprednisolone (or prednisone equivalent), aimed at controlling severe immune-mediated hepatitis and preventing progression to liver failure. Participants will be monitored closely for clinical improvement, laboratory normalization, and adverse events throughout the 56-day treatment period, with continued follow-up through Day 180 to assess long-term outcomes, including relapse, liver failure, survival, and safety.
Drug: Emapalumab
Participants on the Intervention Cohort will receive a combination of immunomodulatory regimen using emapalumab and methylprednisolone (or prednisone equivalent), aimed at controlling severe immune-mediated hepatitis and preventing progression to liver failure.
Incidence of Liver Failure
INR \>2 on two consecutive occasions without hepatic encephalopathy (HE), or INR ≥1.5 with evidence of HE
Time frame: 30, 90, and 180 days after the start of emapalumab
Complete Response (CR)
A complete response (CR) is defined by normalization or near-normalization of liver injury markers and hepatic function. Patients achieving CR will demonstrate an ALT \< 2.5X ULN together with an INR ≤ 1.2.
Time frame: throughout study participation/ up to 180 days
Cytokine and Chemokine Profiling
The cytokine milieu including interferon-γ, interferon-stimulated gene products, TNF-α, IL-6, IL-18, CXCL9, and others will be quantified to define the inflammatory environment at baseline and during treatment.
Time frame: through study participation/ up to 180 days
Emapalumab Immunologic Effects
Change in circulating activated CD8+ T cells from the initiation of emapalumab to Days 7, 14, 30, 60, 90, and 180 of study
Time frame: through study completion/ up to 180 days
Incidence and Severity of Adverse Events
Incidence of all adverse events of all grades as defined by CTCAE version 5.0
Time frame: from first emapalumab dose through study completion, up to 180 days
Population Summary Measure
The population summary measure will be the Complete Response rate, which will be estimated as the number of participants with Complete Response divided by the total number of participants in the efficacy sample population.
Time frame: throughout study participation/ up to 180 days
Time to First Complete Response
Time to first CR will be estimated using time-to-event methods. Death or liver transplant before CR will be treated as competing risks, and cumulative incidence functions will be used to estimate probabilities.
Time frame: throughout study participation/ up to 180 days
Partial Response (PR)
This is defined as an ALT decrease 50% from initiation of emapalumab, but ALT \>2.5X ULN with INR\< 1.2.
Time frame: throughout study participation/ up to 180 days
Sustained Response Off Therapy (SR)
ALT levels remaining \< 2.5X ULN for at least two consecutive months after completion of emapalumab.
Time frame: throughout study participation/ up to 180 days
Non-Response (NR)
Patients are considered non-responders if clinically relevant worsening with progression to liver failure.
Time frame: After 4 doses of emapalumab/ about 2 weeks after start of therapy
Proportion of Patients with Overall Response (CR or PR)
The proportion of patients achieving overall response (OR, defined as CR or PR) will be reported at Week 8 with exact confidence intervals. Missing values will be treated as non-response
Time frame: from first dose of emapalumab to week 8 of therapy
Time to First Overall Response (OR)
Time to first OR will be analyzed using cumulative incidence methods, with death or liver transplant treated as competing risks.
Time frame: throughout study participation/ up to 180 days
Sustained CR Off Therapy at Day 180
The proportion of patients achieving a sustained CR off therapy (SROT) at Day 180 will be summarized with exact confidence intervals. Patients without Day 180 data or therapy information will be considered non-SROT.
Time frame: 180 days on study therapy
Overall Survival with Native Liver
Survival with native liver will be estimated using Kaplan-Meier methods. Survival probabilities and 95% confidence intervals will be presented at each landmark time point.
Time frame: days 30, 60, 90, and 180
Proportion of Patients Receiving Liver Transplantation:
Cumulative incidence of transplant will be calculated at Days 30, 90, and 180, with death as a competing risk.
Time frame: days 30, 90, and 180
Change in Systemic Inflammatory Markers
Longitudinal changes in sIL2R, and CXCL9 will be evaluated using mixed-effects models for repeated measures.
Time frame: throughout study participation/ up to 180 days
Change in Circulating Activated CD8+ T Cells
Changes in activated CD8+ T cells over time will be analyzed similarly with mixed-effects models, supplemented by graphical summaries.
Time frame: throughout study participation/ up to 180 days
Corticosteroid Exposure and Time to Discontinuation
Cumulative corticosteroid exposure (prednisone equivalents) will be summarized descriptively. Time to discontinuation will be estimated using Kaplan-Meier methods, with competing-risk analyses considering death or transplant.
Time frame: throughout study participation/ up to 180 days
Incidence of Hepatitis Relapses
Defined as ALT re-elevation with concurrent sIL2R and CXCL9 rise. Time-to-relapse will be summarized with cumulative incidence functions.
Time frame: After initial improvement during weaning or cessation of therapy, up to Day 180
Plan to share: Yes — Study participant research data, which is for purposes of statistical analysis and scientific reporting, will be stored. This will not include the participant's contact or identifying information. Rather, individual participants and their research data will be identified by a unique study identification number. The study data entry and study management systems used by clinical sites and research staff will be secured and password protected. Neither data nor specimens will be shared across participating sites. Deidentified data that supports the findings of this study will be made available by the Principal Investigator, upon reasonable request. At the end of the study, all records will continue to be kept in a secure location for as long a period as dictated by local IRB and Institutional regulations. All study databases will be de-identified and archived.
No publications or documents are linked to this record.
This study is not yet recruiting, as verified in Jul 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Emapalumab
Children's Healthcare of Atlanta