Itolizumab + Corticosteroids for Acute Graft-Versus-Host Disease

Recruiting at 142 trial locations

Overseen By Clinical Trial Manager

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Equillium

Must be taking: Corticosteroids

Must not be taking: Immunosuppressants

Disqualifiers: Relapsed malignancy, cGVHD, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 7

Duration: 14 weeks

158 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment option for people with severe acute graft-versus-host disease (aGVHD), a condition that can occur after a stem cell transplant. Researchers aim to determine if itolizumab (an anti-CD6 monoclonal antibody), combined with corticosteroids, is more effective than a placebo (a harmless substance with no active treatment) in treating aGVHD. Participants will receive either itolizumab or a placebo through an IV every two weeks for a total of seven doses. The trial seeks individuals aged 12 years or older who have undergone a stem cell transplant and are currently experiencing severe aGVHD. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to a treatment that could soon become widely available.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must not use immunosuppressants other than corticosteroids for treating aGVHD. You also need to be on a specific dose of corticosteroids when starting the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that itolizumab is generally safe. In earlier studies, itolizumab did not increase infections or sepsis, a serious condition where the body reacts severely to an infection. Although some serious health issues were reported, they were not linked to itolizumab. For instance, none of the 11 deaths were related to the drug.

Overall, itolizumab appears well-tolerated by patients, meaning most people can take it without major problems. However, like any treatment, side effects might occur. Discuss any concerns with a doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatment for acute graft-versus-host disease, which primarily relies on corticosteroids to suppress the immune response, itolizumab offers a novel approach. Itolizumab is a monoclonal antibody that specifically targets and modulates the activity of the CD6 receptor on T cells, which are key players in the immune system's attack on the host tissues. Researchers are excited about it because it could potentially reduce the severity of graft-versus-host disease with fewer side effects compared to traditional steroid treatments. Additionally, its targeted action might lead to more effective and quicker relief for patients suffering from this condition.

What evidence suggests that itolizumab combined with corticosteroids could be effective for acute graft-versus-host disease?

Research has shown that itolizumab may help treat acute graft-versus-host disease (aGVHD). Studies have found that itolizumab, a type of antibody, is safe and leads to significant health improvements. In the EQUATE study, patients experienced quick and lasting positive responses, surpassing those of other treatments. Although itolizumab did not achieve the main goal in the EQUATOR trial, it still demonstrated significant long-term benefits for patients with aGVHD. In this trial, participants may receive itolizumab alongside corticosteroids, suggesting it could be an effective treatment option. ^{1 2 5 6 7}

Who Is on the Research Team?

Chief Development Officer

Principal Investigator

Equillium, Inc.

Are You a Good Fit for This Trial?

This trial is for individuals over 12 years old and heavier than 40kg who have had a bone marrow transplant and are now facing a severe reaction called acute Graft Versus Host Disease (aGVHD). They should have started steroid treatment within the past 72 hours. People with chronic GVHD, other ongoing treatments for aGVHD besides steroids, or those with certain types of cancer relapse or persistent disease aren't eligible.

Inclusion Criteria

I have had a stem cell transplant from a donor.

I am 12 years or older and weigh more than 40kg.

I started corticosteroid treatment for aGVHD less than 3 days ago and will get a specific dose on Day 1.

Exclusion Criteria

I am taking immunosuppressants other than corticosteroids for aGVHD.

I had an emergency cell transplant due to cancer returning after a stem cell transplant.

My cancer has returned or is getting worse, except for skin cancer or early-stage breast cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive itolizumab or placebo in combination with corticosteroids, administered intravenously every 2 weeks for a total of 7 doses

14 weeks

7 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

365 days

What Are the Treatments Tested in This Trial?

Interventions

• Corticosteroids
• Itolizumab

Trial Overview The study is testing Itolizumab in combination with corticosteroids against a placebo plus corticosteroids to see which is better as an initial treatment for severe forms of aGVHD following bone marrow transplantation.

How Is the Trial Designed?

Group I: Itolizumab (EQ001) Experimental Treatment 1 Intervention

Itolizumab (EQ001) administered in a blinded fashion by intravenous infusion every 2 weeks for a total of 7 doses.

Group II: EQ001 Placebo Placebo Group 1 Intervention

EQ001 Placebo administered in a blinded fashion by intravenous infusion every 2 weeks for a total of 7 doses

Who Is Running the Clinical Trial?

Equillium

Lead Sponsor

Trials

7

Recruited

340+

Biocon Limited

Industry Sponsor

Trials

14

Recruited

890+

Published Research Related to This Trial

Itolizumab, a CD6 monoclonal antibody used for autoimmune diseases, has a lower binding affinity compared to other CD6 mAbs, which may influence its effectiveness in modulating T-cell activity.

Both CD6 domain 1 and domain 3 mAbs can trigger interleukin-2 production, but domain 1 mAbs are less effective at blocking the binding of the CD6 ligand CD166 compared to soluble CD166, suggesting different therapeutic potentials for these antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD6 monoclonal antibodies differ in epitope, kinetics and mechanism of action. Garner, LI., Hartland, A., Breuning, J., et al.[2022]

In a study of 48 patients undergoing allogeneic stem-cell transplantation, the use of tocilizumab, an anti-interleukin-6 receptor monoclonal antibody, resulted in a low incidence of grade 2-4 acute graft-versus-host disease (GVHD) at 12%, suggesting its efficacy in reducing this serious complication.

The treatment preserved immune reconstitution while modifying certain pathogenic pathways, indicating that targeting interleukin 6 could be a promising strategy to prevent acute GVHD without compromising the immune system's recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Addition of interleukin-6 inhibition with tocilizumab to standard graft-versus-host disease prophylaxis after allogeneic stem-cell transplantation: a phase 1/2 trial. Kennedy, GA., Varelias, A., Vuckovic, S., et al.[2022]

Itolizumab, an anti-CD6 monoclonal antibody, demonstrated a good safety profile in a phase I study with 15 patients, showing no severe adverse events or signs of immunosuppression.

Over 80% of patients experienced objective clinical responses after treatment, indicating preliminary efficacy and sustained benefits from this novel therapy for rheumatoid arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A clinical exploratory study with itolizumab, an anti-CD6 monoclonal antibody, in patients with rheumatoid arthritis. Rodriguez, PC., Torres-Moya, R., Reyes, G., et al.[2021]

Itolizumab, a monoclonal antibody targeting CD6, effectively reduces the activation and differentiation of T cells into Th17 cells, which are involved in autoimmune diseases like psoriasis, by decreasing IL-17 production and inhibiting key transcription factors.

The mechanism of action for Itolizumab includes direct inhibition of CD6 receptor hyper-phosphorylation, leading to reduced activity of associated signaling proteins, making CD6 a promising target for therapies aimed at modulating autoimmune responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T cell activation and differentiation is modulated by a CD6 domain 1 antibody Itolizumab. Bughani, U., Saha, A., Kuriakose, A., et al.[2018]

In a study involving 70 COVID-19 patients, itolizumab, an antibody targeting CD6, showed promise in improving lung function and reducing oxygen requirements, particularly in patients with severe cases.

The treatment was associated with a low 14-day mortality rate of 4% for moderate and 18% for severe patients, suggesting that timely administration of itolizumab may help mitigate the hyperinflammatory response linked to COVID-19.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of COVID-19 patients with the anti-CD6 antibody itolizumab. Caballero, A., Filgueira, LM., Betancourt, J., et al.[2022]

In a study involving 95 patients after allogeneic cell transplantation, it was found that the CD6-ALCAM pathway plays a crucial role in T-cell activation and that itolizumab, an anti-CD6 monoclonal antibody, effectively inhibited T-cell activation and proliferation before the onset of acute graft-versus-host disease (aGvHD).

The study suggests that targeting the CD6-ALCAM pathway with itolizumab could be a promising strategy for controlling aGvHD, as it significantly reduced T-cell activation, although its effectiveness decreased after aGvHD onset.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phenotypic and functional characterization of the CD6-ALCAM T-cell co-stimulatory pathway after allogeneic cell transplantation. Rambaldi, B., Kim, HT., Arihara, Y., et al.[2022]

Itolizumab, a humanized monoclonal antibody targeting CD6, has shown favorable clinical effects and a good safety profile in treating autoimmune diseases like rheumatoid arthritis and psoriasis, based on clinical studies in Cuban patients.

The mechanism of action for itolizumab involves steric blocking of the CD6-CD166 interaction, suggesting it modulates T cell signaling and has immunomodulatory and anti-inflammatory effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Targeting of CD6 in Autoimmune Diseases: A Review of Cuban Clinical Studies with the Antibodies IOR-T1 and Itolizumab. Hernández, P., Moreno, E., Aira, LE., et al.[2019]

In a clinical trial involving 30 rheumatoid arthritis patients, the combination of itolizumab and methotrexate significantly reduced T cell subpopulations and proinflammatory cytokine levels for at least 12 weeks after treatment, indicating effective immunological modulation.

The study found no anti-idiotypic antibody response to itolizumab, supporting its safety and suggesting that targeting the CD6 molecule could be a promising therapeutic strategy for rheumatoid arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunological evaluation of rheumatoid arthritis patients treated with itolizumab. Aira, LE., Hernández, P., Prada, D., et al.[2018]

Inolimomab, a monoclonal antibody targeting IL-2Ralpha, shows promise as a first-line treatment for corticosteroid-resistant acute graft-versus-host disease (GvHD) in a study of 21 patients, with pharmacokinetic and pharmacodynamic properties characterized through a two-compartmental model.

The study identified a dose-effect relationship for inolimomab, linking drug concentration to treatment response, which is crucial for optimizing dosage in future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exposure-effect population model of inolimomab, a monoclonal antibody administered in first-line treatment for acute graft-versus-host disease. Dartois, C., Freyer, G., Michallet, M., et al.[2018]

Citations

1. equilliumbio.com equilliumbio.com/investors/press-releases/news-details/2025/Equillium-Announces-Results-of-the-Phase-3-EQUATOR-Study-of-Itolizumab-in-First-Line-Treatment-of-Patients-with-Acute-Graft-Versus-Host-Disease/default.aspx

Equillium Announces Results of the Phase 3 EQUATOR ... The Phase 3 EQUATOR study in first-line aGVHD demonstrated a favorable safety and tolerability profile, and clinically meaningful longer-term outcomes.

2. tandem.confex.com tandem.confex.com/tandem/2023/meetingapp.cgi/Paper/21931

Final Safety and Efficacy Results from Equate, an Open- ... Here we present final study results, including long-term follow-up data for up to one year, from EQUATE (NCT03763318), a Phase 1b study of itolizumab in ...

3. onclive.com onclive.com/view/itolizumab-misses-primary-end-point-in-acute-gvhd-but-shows-meaningful-improvements-in-other-areas

Itolizumab Misses Primary End Point in Acute GVHD but ... Itolizumab failed to meet the primary endpoint of day-29 CR rate in the EQUATOR trial for aGVHD but showed significant improvements in longer- ...

4. gvhdhub.com gvhdhub.com/medical-information/positive-interim-results-of-the-equate-studyitolizumab-for-acute-graft-versus-host-disease

Positive interim results of the EQUATE study—Itolizumab ... The results suggest that the first-in-class anti-CD6 monoclonal antibody, itolizumab, is well tolerated in patients with acute graft-versus-host ...

5. targetedonc.com targetedonc.com/view/phase-3-equator-study-to-initiate-itolizumab-treatment-in-patients-with-agvhd

Phase 3 EQUATOR Study to Initiate Itolizumab Treatment ... Itolizumab demonstrated impressive complete response rates in the EQUATE study that were both rapid and durable, and which compared favorably to ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05823675

Safety and Clinical Activity of Itolizumab in aGVHD To evaluate the safety, tolerability, PK, PD, and clinical activity of Itolizumab in subjects with Newly diagnosed Acute Graft Versus Host Disease(aGVHD).

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03763318

NCT03763318 | A Study to Evaluate the Safety, Tolerability ... This is a multi-center study to evaluate the safety, tolerability, PK, PD, and clinical activity of EQ001 in subjects with Acute Graft Versus Host Disease ( ...