A Phase 2/3 Randomized Double‑Blind Study of Inebilizumab for Safety and Tolerability in Patients with Autoimmune Hepatitis

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What is this study about?

Autoimmune Hepatitis is a rare condition in which the body’s immune system mistakenly attacks the liver, causing inflammation and damage. In this research, participants receive an intravenous infusion of a medication called inebilizumab, while other participants receive a matching infusion that does not contain the active drug.

The study’s goal is to see how safe and well‑tolerated the medication is for people with this liver disease. Participants are randomly assigned to one of the two groups, and neither the participants nor the study staff know which infusion is being given. Over a period of about six months, participants receive several infusions and have regular check‑ups to monitor liver function, side effects, and overall health. The trial ends after the final follow‑up visit, at which point the collected information is analyzed.

1 enrollment and baseline assessments

after joining the study, you will sign an informed consent form and undergo initial medical examinations.

these examinations include blood tests, liver imaging, and a review of any current medications such as prednisone.

2 randomization to study medication

the study team will assign you, by chance, to receive either inebilizumab or a placebo.

you will not know which one you receive because the study is double‑blind.

3 first intravenous infusion

you will receive a single infusion through a vein (intravenous infusion).

if assigned to the active group, the infusion contains 100 mg of inebilizumab dissolved in a solution for infusion.

if assigned to the placebo group, the infusion contains an identical‑appearing solution without any active drug.

4 scheduled follow‑up infusions during the 26‑week treatment period

additional infusions will be given according to the study schedule throughout the first 26 weeks.

each infusion is administered intravenously and follows the same dosage as the first infusion.

5 regular laboratory monitoring

at each study visit you will have blood drawn to check liver enzymes, especially ALT (alanine aminotransferase),

the number of B cells in your blood, and the concentration of inebilizumab if you are in the active group.

6 assessment of prednisone dose

your prednisone (or equivalent steroid) dose will be reviewed at every visit to ensure it remains at or below 5 mg per day, as required by the study protocol.

7 safety monitoring for adverse events

throughout the 26‑week period you will be asked about any new symptoms or health problems.

the study team will record any adverse events, serious adverse events, or events of special interest.

8 primary and secondary outcome evaluation at week 26

at the end of week 26 a comprehensive assessment will be performed.

the evaluation includes checking whether ALT has returned to normal, whether the modified histologic activity index (mHAI) is 3 or lower, and whether the prednisone dose is stable at 5 mg per day or less.

additional measurements such as B‑cell counts and drug levels (if applicable) will also be taken.

9 optional continuation into part 2 of the study

participants who meet specific criteria may be invited to continue in a second phase of the trial.

this phase continues to monitor liver enzyme levels, steroid use, and safety for a longer period.

10 final study visit and completion

after the designated treatment period (up to 78 weeks for some participants) a final visit will be scheduled.

the visit includes a last set of blood tests, a review of any remaining adverse events, and collection of study data.

Who Can Join the Study?

Signed informed consent: You must sign a document that explains the study and shows you agree to take part.
Age between 18 and 75 years (or the legal adult age in your country, whichever is older) at the time you sign the consent form.
You must have had an inadequate response to at least nine months of standard treatment for autoimmune hepatitis, meaning your liver enzyme ALT (a blood test that shows liver damage) is still at least twice the normal upper limit (ULN) after taking standard medicines such as prednisone (a steroid), azathioprine (AZA), 6‑mercaptopurine (6‑MP), or mycophenolate mofetil (MMF). Alternatively, you may be unable to tolerate these medicines because side effects forced you to stop them or prevented you from reaching the needed dose.
Your liver enzyme ALT level at screening must be between 2 × ULN and 7 × ULN. This shows active disease but not an extreme level.
You need a liver biopsy that confirms autoimmune hepatitis with a diagnostic score of 7 or higher, performed within the 90 days before randomization, and the biopsy must show an mHAI score of at least 5 (a measure of inflammation severity).
Your medication doses must be stable: no increase in glucocorticoid (GC) dose (such as prednisone) during the 28 days before the baseline biopsy and through the day you are randomized; and you must have been on the highest tolerated dose of either AZA or 6‑MP or MMF/MPA for at least 12 weeks before screening and continue that stable dose unless safety reasons require a change.
You must use a reliable form of contraception (birth control) during the study treatment and for six months after the last dose of the study drug.

Who Cannot Join the Study?

Having another liver disease that overlaps with autoimmune hepatitis (for example, primary biliary cholangitis, primary sclerosing cholangitis, or lupus‑related liver disease) that meets specific overlap criteria.
Blood test results that are too low or too high, such as hemoglobin less than 7.5 g/dL (low red blood cells), neutrophils less than 1200 per mm³ (low white blood cells), platelets less than 150 × 10⁹/L, INR greater than 1.3 (a clotting test), CD19+ B cells less than 40 per µL, serum albumin less than 35 g/L, bilirubin above the normal range, alkaline phosphatase more than 1.5 times the upper limit, or AST more than 7 times the upper limit.
Having an active, serious infection at the time of enrollment.
Testing positive for HIV infection.
Having acute liver failure (sudden severe liver dysfunction with clotting problems or brain changes).
Being allergic to any part of the study drug inebilizumab or having had a severe allergic reaction (anaphylaxis) to similar treatments.
Being allergic to or unable to tolerate the medicines used to prevent infusion reactions (such as acetaminophen, diphenhydramine, or steroids).
Having an active cancer or a cancer that was treated within the past 10 years (with a few exceptions for certain skin, breast, prostate, or thyroid cancers that were cured long ago).
Having taken tumor‑necrosis‑factor (TNF) inhibitors (e.g., infliximab, adalimumab) within the last 6 months.
Having taken strong immune‑suppressing drugs like tacrolimus, cyclosporine, methotrexate, or everolimus within the last 6 weeks.
Having taken any other experimental drug within 12 weeks (or five half‑lives) before screening.
Having a known immune‑deficiency disorder.
Being unable to stop long‑term steroid (glucocorticoid) use because of adrenal insufficiency or other steroid‑dependent conditions.
Receiving any vaccine within 4 weeks before the first study dose.
Regularly using medicines that can damage the liver.
Having a current or past hepatitis B or hepatitis C infection, even if previously treated.
Currently taking high‑dose steroids (more than 20 mg prednisone per day) or high doses of certain immune‑suppressing pills (azathioprine, 6‑mercaptopurine, mycophenolate mofetil, or mycophenolic acid) above the listed limits.
Taking any other immune‑suppressing treatment besides the allowed ones (azathioprine, 6‑mercaptopurine, mycophenolate).
Having undetectable drug levels of azathioprine or mycophenolate during screening unless not taking those drugs.
Starting any new herbal or dietary supplement within 4 weeks before the first dose.
Currently participating in another clinical trial or having finished another trial less than 30 days (or five half‑lives) ago.
Being unable to safely have a liver biopsy.
Having metabolic‑associated steatohepatitis (MASH) identified on the liver biopsy.
Likely unable to complete all study visits and procedures.
Having any other serious medical condition that the doctor thinks makes participation unsafe.
Being pregnant, breastfeeding, or planning to become pregnant during the study period and for 6 months after the last dose.
Having a positive pregnancy test at screening.
Having active or untreated latent tuberculosis (TB) infection.
Unwilling to avoid donating blood or plasma while in the study.
Having uncontrolled alcohol use disorder (more than 2 drinks per day for men or 1 drink per day for women for at least 3 months).
Having had serious infections requiring hospitalization or IV antibiotics in the past year.
Having major surgery within 8 weeks before screening.
Having had two or more episodes of shingles (herpes zoster) or other serious opportunistic infections in the past year.
Having severe heart, lung, endocrine, gastrointestinal, blood, nervous system, psychiatric, or other systemic disease that puts you at high risk.
Experiencing any life‑threatening infection, sepsis, or fever with very low neutrophils.
Experiencing any serious allergic reaction or severe infusion‑related reaction during the study.
Having any grade 4 serious adverse event (the most severe type of side effect).
Having decompensated cirrhosis (advanced liver scarring with complications such as fluid buildup, confusion, bleeding, or kidney problems) or a history of such.
Having an absolute neutrophil count below 800 cells/µL confirmed by repeat testing.
Not following the study protocol well enough, as judged by the investigators.
Having a history of drug‑induced liver injury (DILI) from any medication.
Having received any B‑cell‑depleting biologic therapy (e.g., rituximab, ocrelizumab, inebilizumab) within the last 6 months.
Having received other biologic immune‑modulating drugs (e.g., belimumab, abatacept) within the last 6 months.
Having an estimated kidney filtration rate (eGFR) below 45 mL/min/1.73 m² (indicating reduced kidney function).

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country
IRCCS Humanitas Research Hospital	Rozzano	Italy
Unidade Local De Saúde De Santa Maria, E.P.E.	Lisbon	Portugal
Centro Hospitalar Universitario Sao Joao E.P.E.	Porto	Portugal
Katholieke Universiteit te Leuven	Leuven	Belgium
Université Libre de Bruxelles – Hôpital Erasme	Brussels	Belgium
University Hospital Jena KöR	Jena	Germany

Other Sites

Site Name	City	Country
University Hospital Ostrava	Ostrava	Czechia
Hospital General Universitario Gregorio Maranon	Madrid	Spain
Centre Hospitalier Universitaire De Nantes	Nantes	France
Bekes Varmegyei Koezponti Korhaz	Gyula	Hungary
Meditsinski Tsentar Arkus Medikal A.D.	Veliko Tirnovo	Bulgaria
Assistance Publique Hopitaux De Paris	Paris	France
Axspkrv Ozhlgscfiiz de Pxcspi	Padua	Italy
Fbrrnwjb Nxkfftdic Poyio	Plzen	Czechia
Lkvjm Glkzvmr Hwveguwu Od Aesxji	Athens	Greece
Avev Gwvzow Ozldjczo Mtnipsecgarvv Nydnfrqi	Milan	Italy
Acdhjaamr Ueb	Amsterdam	The Netherlands
Fndgdpza Ntiaoadqc Kvgdcqasc Vhddxzdjc	Prague	Czechia
Cejuku Hprnkizowe E Uayykrwlmfsxb Dw Cbmfvaq Esgfwa	Coimbra	Portugal
Aoxkwyj Orqcrugjfmz Uafzclfsazfyc Ojfadjjl Rjtspnw	Foggia	Italy
Vlfpwwuzd Fblumovc Nthbzuvrv V Pmqta	Prague	Czechia
Apfmxzf Uufvn Syyirfvkm Lvatns Ds Bnqkpsk	Bologna	Italy
Cuqopx Habmfyycch Urwvccqhywucd Dd Sqqxh Aqjpsgn Ejnwbv	Porto	Portugal
Atsgndx Ogdzaomnfnh Pfds Gfbifltq Xlhbd	Bergamo	Italy
Iihzjibcw Fzb Ctnklpzk Arw Erubylzjiwig Moletyrr	Prague	Czechia
Urfgpbzoxmnq Zehgoslfcr Gukn	Gent	Belgium
Adcgarp Oyiejgsdvfr Uvpfonfdbtmok Pkzdnyhvhzc Pvayg Gnnmomjz	Palermo	Italy
Fdkczjmkgw Iqdfn Son Goerwcw Dzl Tebcjtv	Monza	Italy
Uafbnwpejx Gytsbcv Himhawpn Akpmdnb Gxoajwq Hsgmbmqk Oy Wvax Ajzbtd H Akdi Vbjmwnm	Chaidari	Greece
Hwhedlvg Vqdb duapvgvq	Barcelona	Spain
Ughdorljaagmcnrzrngfq Tvwiqvetb Awb	Tuebingen	Germany
Hejuaaca Cuyedz Dv Bkxjaikuq	Barcelona	Spain
Uwsodslxyv Mttvmys Cgcphd Hhnmfwdhoonwelbvm	Hamburg	Germany
Hhdnyltp Ukoeydtyhqcld Dj Lj Pfllyldq	Madrid	Spain
Ffpxzlcew Pplc Lf Ifiiotjqvtyqb Babkvgads Dlq Hgsmcwqe Uqnjzvrakgmtd Lm Pct	Madrid	Spain
Hddypvxo Udcyxfqhxnqov Vmteaw Du Lg Vziulxro	Malaga	Spain
Ix Cvwcrm	Myslowice	Poland
Smzednskqlz Pblsxxgeu Saxzxbv Kzpagqcdj Nm 4 W Lemhinfd	Lublin	Poland
Utkbznnofrzbie Csnbuth Kplnajpmn Wcpegzlvucbcy Uqinzxptwvqw Mbafitlmnt	Warsaw	Poland
Uxtyfgcrhi Og Dfxvelkx	Debrecen	Hungary
Oxostw Etqlameaobtui Cusieff Kqgs	Dunaújváros	Hungary
Hmgqrlzs Pquy Bxvmesh	Villejuif	France
Csiqhl Hdjahxtnmnc Uwwbdnemgfxts Di Mweoddjiqvt	Montpellier	France
Unovscarac Oi Pdzc	Pecs	Hungary
Mjyxayqj Mjljbyn Adkkyaa	Pleven	Bulgaria
Clxemr Hngwzyoybny Lxzo Srs	Pierre Benite	France
Mpmf Snati Kwzevli Etj	Plovdiv	Bulgaria

Trial status

Country	Status	Recruitment Start
Belgium	Not yet recruiting	01.10.2026
Bulgaria	Not yet recruiting	01.10.2026
Czechia	Not yet recruiting	01.10.2026
France	Not yet recruiting	01.10.2026
Germany	Not yet recruiting	01.10.2026
Greece	Not yet recruiting	01.10.2026
Hungary	Not yet recruiting	01.10.2026
Italy	Not yet recruiting	01.10.2026
Poland	Not yet recruiting	01.10.2026
Portugal	Not yet recruiting	01.10.2026
Spain	Not yet recruiting	01.10.2026
The Netherlands	Not yet recruiting	01.10.2026

Trial locations

Investigated Drugs:

Inebilizumab

Uplizna is a medication that contains a type of protein called a monoclonal antibody. It works by attaching to certain immune cells (called B‑cells) that can mistakenly attack the liver in autoimmune hepatitis. By reducing the activity of these cells, the drug may help calm the immune system and protect the liver. In the study, Uplizna is given through an IV (intravenous) infusion, and researchers are watching closely to see how safe it is and how well patients can tolerate it.

Investigated Diseases:

Autoimmune hepatitis

Autoimmune hepatitis – Autoimmune hepatitis is a chronic inflammatory liver disease in which the immune system mistakenly attacks liver cells. It often starts with mild fatigue, abdominal discomfort, and elevated liver enzymes. Over time, persistent inflammation can cause scarring (fibrosis) and may progress to cirrhosis. The condition frequently shows episodes of increased activity (flares) followed by periods of lower activity (remission). It is more common in women and may occur alongside other autoimmune disorders. Ongoing inflammation can gradually impair liver function if the disease remains active.

Trial ID:

2025-522393-37-00

Protocol code:

20240237

Trial Phase:

Therapeutic use (Phase IV)

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A Phase 2/3 Randomized Double‑Blind Study of Inebilizumab for Safety and Tolerability in Patients with Autoimmune Hepatitis

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?