Evaluation of Itolizumab and Corticosteroids for Initial Management of Acute Graft Versus Host Disease in a Phase 3 Randomized Controlled Trial

Trial ID: 2024-516064-28-00
Protocol: EQ-100-02
Sponsor: Equillium Inc.

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Diseases & Conditions

Graft versus host disease Allogenic stem cell transplantation

Objectives

The primary objective of this Phase 3, randomized, double-blind, placebo-controlled multicenter study is to assess the **efficacy** of itolizumab versus placebo as initial therapy for acute Graft Versus Host Disease (aGVHD) in combination with corticosteroids in achieving early disease response. This is clinically relevant as aGVHD is a serious complication following bone marrow transplantation, and effective early intervention can significantly impact patient outcomes.

Secondary objectives include:

Evaluating the durability of response to itolizumab versus placebo as initial therapy for aGVHD in combination with corticosteroids.
Assessing systemic corticosteroid use in subjects treated with itolizumab versus placebo.
Evaluating the impact of itolizumab versus placebo on other clinically relevant efficacy measures, including survival outcomes and chronic Graft Versus Host Disease (cGVHD) incidence.
Assessing the safety and tolerability of itolizumab versus placebo as initial therapy for aGVHD in combination with corticosteroids.

Participants

The clinical trial involves a total of **101 participants** diagnosed with **Acute Graft Versus Host Disease** (aGVHD). The study population includes both male and female subjects, aged 12 years and older, with a minimum weight of over 40 kg. Participants have undergone an initial allogeneic hematopoietic stem cell transplantation (HSCT) for any indication, with evidence of myeloid engraftment. The trial includes individuals with a clinical diagnosis of aGVHD Grades III-IV or Grade II with lower gastrointestinal involvement, as per the Mount Sinai Acute GVHD International Consortium (MAGIC) grading criteria. The trial population was selected based on specific inclusion criteria, including the initiation of systemic corticosteroid treatment prior to study drug dosing. The study does not specify particular lifestyle considerations such as diet or physical activity. Both vulnerable and non-vulnerable populations are included in the trial.

Plans and Procedures

The clinical trial is a **Phase 3**, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy of **itolizumab** in combination with corticosteroids for the initial treatment of **Acute Graft Versus Host Disease** (aGVHD). The trial aims to assess the efficacy of itolizumab versus placebo in achieving an early disease response. Participants will be randomly assigned to receive either itolizumab or a matching placebo, both administered as a **solution for infusion** via **intravenous use**. The trial is expected to last until November 2025, with recruitment having commenced in March 2022.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, history of allogeneic hematopoietic stem cell transplantation (HSCT), and clinical diagnosis of aGVHD. The primary endpoint is the complete response rate at Day 29, with secondary endpoints including overall response rate at Day 29 and durable complete response rate from Day 29 through Day 99. The expected length of participant involvement is up to 84 days, corresponding to the maximum treatment period for itolizumab. Conditions that may lead to early termination from the study include failure to meet inclusion criteria, adverse events, or withdrawal of consent.

Treatment

The clinical trial involves the administration of **itolizumab**, an experimental medication, in the form of a **solution for infusion**. Itolizumab is a protein-based therapeutic agent developed by Equillium, Inc. The medication is administered intravenously, with a maximum daily dose of 1.6 mg/kg and a total maximum dose of 6.4 mg/kg over the course of the treatment. The maximum treatment period is 84 days. The primary objective of the trial is to evaluate the efficacy of itolizumab in combination with corticosteroids for the initial treatment of acute Graft Versus Host Disease (aGVHD).

In addition to the experimental treatment, the study includes the use of an **itolizumab-matching placebo**. The placebo is designed to mimic the appearance and administration route of the active medication, ensuring the study remains double-blind. The placebo is also administered intravenously as a solution for infusion, maintaining consistency with the experimental treatment. The use of a placebo allows for a controlled comparison to assess the true efficacy of itolizumab in achieving early disease response in aGVHD patients.

Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment protocol. The study is conducted under strict clinical guidelines to maintain the integrity and reliability of the trial results. The combination of itolizumab or placebo with corticosteroids represents the treatment regimen under investigation, with the aim of providing insights into the potential benefits of itolizumab for patients with aGVHD.

Efficacy

The efficacy of the investigational product, **itolizumab**, will be assessed in a Phase 3, randomized, double-blind, placebo-controlled multicenter study. The primary endpoint for evaluating efficacy is the Complete Response rate at Day 29. Secondary endpoints include the Overall Response rate at Day 29 and the Durable Complete Response rate from Day 29 through Day 99. These endpoints are designed to measure the effectiveness of itolizumab in combination with corticosteroids for the initial treatment of acute Graft Versus Host Disease (aGVHD).

Data collection will occur at specified timepoints, with the primary assessment at Day 29 and additional evaluations extending through Day 99 to capture the durability of the response. The study will utilize the Mount Sinai Acute GVHD International Consortium (MAGIC) grading criteria to ensure consistent and validated assessment of aGVHD severity and response to treatment. The trial aims to determine the efficacy of itolizumab in achieving early disease response when used as initial therapy in combination with corticosteroids.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Age ≥12 years and >40 kg at informed consent/assent. Subjects <18 years may only enroll if locally permitted.
Has had an initial allogeneic HSCT for any indication using any graft source, donor source, conditioning regimen intensity or prophylaxis. NOTE: 2 allogeneic HSCTs may be allowed if GVHD did not occur after the first HSCT.
Has evidence of myeloid engraftment, defined as an absolute neutrophil count ≥500/mm3 (or ≥0.5 × 10exp9/L) achieved and sustained for 3 laboratory values obtained on different days. Laboratory values prior to Screening may be used.
Has a clinical diagnosis of aGVHD Grades III-IV or Grade II with LGI involvement based on Mount Sinai Acute GVHD International Consortium (MAGIC) grading criteria - at Screening and randomization. Biopsies to confirm aGVHD should be obtained but are not required and should not delay entry into the study.
Began initial systemic corticosteroid treatment with ≥ 1mg/kg/day methylprednisolone or equivalent for aGVHD ≤72 hours prior to the start of study drug dosing AND must receive 2 mg/kg/day methylprednisolone or equivalent on Day 1.

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Exclusion Criteria

Has evidence of morphological relapsed, progressive, persistent, or untreated malignancy, with the exception of nonmelanoma skin cancer and in situ ductal carcinoma of the breast.
Has an unplanned donor lymphocyte infusion for persistent or recurrent malignancy after HSCT.
Has evidence of persistent molecular disease requiring treatment (eg, standard chemotherapy or tyrosine kinase inhibitors) that was not specified prior to HSCT.
Has evidence of cGVHD or overlap syndrome, as defined by 2014 NIH Consensus Criteria.
Is using immunosuppressants other than corticosteroids for the treatment of aGVHD. Continued use of immunosuppressants as GVHD prophylaxis agents is permitted.
Has received any systemic corticosteroids of >0.5 mg/kg/day methylprednisolone or equivalent for any indication other than aGVHD within 7 days before the onset of aGVHD. Systemic corticosteroids administered as premedication before blood product transfusions or IV medications to prevent infusion-related reactions are allowed.
Has a clinically active, uncontrolled bacterial, viral, or fungal infection, despite adequate treatment. No signs of progression of the infection can be present at randomization. Asymptomatic cytomegalovirus (CMV), Epstein–Barr virus (EBV), or human Herpesvirus 6 (HHV-6) viremia based on viral load or a viral load that is declining with treatment does not constitute a clinically active infection.
Other Protocol-defined criteria apply.

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
Belgium	Not Recruiting	23 Mar 2022	10
France	Not Recruiting	23 Mar 2022	17
Germany	Not Recruiting	23 Mar 2022	22
Italy	Not Recruiting	23 Mar 2022	18
Portugal	Not Recruiting	23 Mar 2022	2
Spain	Not Recruiting	23 Mar 2022	30