Inebilizumab for the Treatment of Patients With Type 1 Autoimmune Pancreatitis

Type 1 autoimmune pancreatitis (AIP) is a manifestation of IgG4-related disease and is associated with a high relapse rate. Long-term treatment with glucocorticoids and conventional immunosuppressants can cause significant adverse effects. Inebilizumab is a CD19-targeted B-cell-depleting agent that acts on the B-cell lineage, including plasmablasts. This study aims to further investigate its efficacy and safety in patients with type 1 AIP.

This prospective, multicenter, single-arm, open-label study plans to enroll a total of 50 patients with confirmed type 1 AIP across 14 participating centers in China. Both newly diagnosed patients and patients with relapsing disease are eligible, provided they meet the study's eligibility criteria. Prior treatment with glucocorticoids or immunosuppressants and a history of relapse are not prerequisites for enrollment.

The primary objective is to assess whether inebilizumab can reduce the relapse rate within 32 weeks in patients with type 1 AIP. Secondary objectives are to assess its effects on glucocorticoid use, serum IgG4 levels, B-cell counts, and other immune cells.

All participants will receive inebilizumab and follow a standardized glucocorticoid tapering regimen. Glucocorticoids will initially be administered at 30 mg/day for one month. The daily dose will then be reduced by one tablet every two weeks until a dose of 20 mg/day is reached. Inebilizumab treatment will subsequently begin, with 300 mg administered intravenously on Day 1 and Day 15. Maintenance treatment will consist of 300 mg administered intravenously every 24 weeks thereafter until the end of the study.

Peripheral blood samples will be collected at baseline before the first dose of inebilizumab, on Day 15, and at Months 6, 12, and 18 after treatment initiation. Lymph node samples will be collected at baseline and at Month 1 or Months 6. These samples will be used for exploratory mechanistic analyses to characterize circulating and tissue immune-cell populations and blood-based biomarkers during treatment and follow-up.

Additional peripheral blood and lymph node samples will be collected if disease relapse occurs during follow-up. These samples will be used to investigate immunological changes associated with disease relapse.

• Inebilizumab (Drug): All patients with type 1 AIP received a standardised glucocorticoid tapering regimen: 30 mg/day for one month, followed by a reduction of one tablet every two weeks to 20 mg/day. Treatment with inelizumab was initiated as follows: Day 1: intravenous infusion of inelizumab 300 mg; Day 15: intravenous infusion of inelizumab 300 mg. Maintenance phase: Thereafter, one infusion of 300 mg every 24 weeks (6 months) until the end of the study. Peripheral blood and lymph node sampling is planned at specified study visits and at disease relapse for exploratory mechanistic analyses, as detailed in the study description.

Primary outcomes

• Recurrence rate within 6 months [6 months]: The proportion of participants with type 1 autoimmune pancreatitis who experience disease relapse within 6 months. Disease relapse will be assessed using clinical symptoms and signs, laboratory findings, including serum IgG4, IgG, liver function, erythrocyte sedimentation rate, complete blood count, and B-cell counts, and contrast-enhanced pancreatic MRI.

Secondary outcomes

• Daily Glucocorticoid Dose [Baseline through 6 months]: The daily dose of glucocorticoids taken by each participant will be recorded in mg/day at baseline and at scheduled follow-up visits. Daily doses will be summarized separately for each assessment time point.
• Serum IgG4 level [Baseline through 6 months]: Serum IgG4 level will be measured at baseline and at scheduled follow-up visits. Measured level will be summarized separately for each assessment time point.
• Peripheral Blood B-Cell Count [Baseline through 6 months]: B-cell counts in peripheral blood will be measured at baseline and at scheduled follow-up visits. Measured counts will be summarized separately for each assessment time point.
• Other immune cells in Peripheral Blood [Baseline through 6 months]: The count of other immune cells in peripheral blood will be measured at baseline and at scheduled follow-up visits. Measured counts will be summarized separately for each assessment time point.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

1. A signed and dated informed consent form;
2. A commitment to adhere to the study protocol and to cooperate throughout the entire study;
3. Aged 18 years or over, regardless of gender;
4. Diagnosed with Type I AIP;
5. Indications for treatment: (1) For symptomatic participants, evidence of pancreatic involvement (e.g. obstructive jaundice, abdominal pain, lower back pain) and extra-pancreatic organ involvement (e.g. jaundice caused by bile duct stricture); (2) Asymptomatic participants with subclinical AIP that may progress to severe, irreversible damage to vital organs (e.g. persistent pancreatic mass, abnormal liver function accompanied by proximal IgG4-related sclerosing cholangitis);
6. Be able to adhere to and cooperate with study interventions, such as taking oral medication;
7. If a woman of childbearing potential, she must have used contraception for at least one month prior to screening and undertake to use contraception throughout the study period and for a specified period following the study's conclusion;

Exclusion Criteria:

Participants meeting any of the following criteria will be excluded from this study:

1. Women who are trying to conceive, are pregnant or are breastfeeding;
2. Those who are unable or refuse to sign the informed consent form;
3. History of mental illness;
4. Allergy to the study intervention;
5. Concurrent malignant tumours;
6. Infectious diseases such as active hepatitis or tuberculosis;
7. Concurrent uncontrolled underlying conditions, such as severe heart failure or respiratory failure.

• Duowu Zou, Doctor, Principal investigator, Ruijin Hospital