Axatilimab + Corticosteroids for Chronic Graft-Versus-Host Disease

Recruiting at 58 trial locations

Overseen By Incyte Corporation Call Center (ex-US)

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Incyte Corporation

Must be taking: Corticosteroids

Must not be taking: CNIs, mTOR inhibitors

Disqualifiers: Multiple allo-HCT, Overlap cGVHD, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: Unknown

Duration: 6 months

240 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will be conducted to compare the efficacy of axatilimab versus placebo in combination with corticosteroids as initial treatment for moderate or severe chronic graft-versus-host disease (cGVHD).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that you should not have started certain treatments like CNIs or mTOR inhibitors within 2 weeks before the trial begins. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug Axatilimab combined with corticosteroids for chronic graft-versus-host disease?

Research shows that Axatilimab, a drug that targets specific immune cells, has been effective in reducing symptoms of chronic graft-versus-host disease in patients who did not respond to other treatments. This suggests it could be a promising option when combined with corticosteroids. ^{1 2 3 4 5}

Is Axatilimab safe for use in humans?

Axatilimab has been studied in a Phase I/II clinical trial for chronic graft-versus-host disease and is generally considered safe, as it is a humanized monoclonal antibody targeting specific immune cells. However, detailed safety data specific to this treatment combination with corticosteroids is limited in the provided research. ^{4 5 6 7 8}

How is the drug Axatilimab with Corticosteroids unique for treating chronic graft-versus-host disease?

Axatilimab combined with corticosteroids is unique because it targets specific immune pathways involved in chronic graft-versus-host disease, potentially offering a novel approach compared to existing treatments like ruxolitinib or abatacept, which have different mechanisms of action. ^{1 2 5 6 9}

Research Team

Albert Assad, MD

Principal Investigator

Incyte Corporation

Eligibility Criteria

This trial is for individuals aged 12 or older who have recently been diagnosed with moderate to severe chronic graft-versus-host disease (cGVHD) after a stem cell transplant from any donor. They must need systemic therapy, have stable blood counts without growth factors, and be willing to prevent pregnancy.

Inclusion Criteria

I am 12 years old or older.

I have a new case of severe chronic GVHD needing systemic treatment.

I have had a stem cell transplant from a donor.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive axatilimab or placebo in combination with corticosteroids as initial treatment for chronic graft-versus-host disease

6 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

Treatment Details

Interventions

• Axatilimab
• Corticosteroids

Trial Overview The study compares the effectiveness of axatilimab plus corticosteroids against a placebo combined with corticosteroids in treating cGVHD as an initial treatment. Participants will randomly receive either the drug or placebo.

Participant Groups

Group I: Placebo + Corticosteroids Experimental Treatment 2 Interventions

Matching placebo and Corticosteroids at the protocol-defined dose.

Group II: Axatilimab + Corticosteroids Experimental Treatment 2 Interventions

Axatilimab and Corticosteroids at the protocol-defined dose.

Axatilimab is already approved in United States for the following indications:

Approved in United States as Axatilimab for:

• Chronic Graft-Versus-Host Disease

Who Is Running the Clinical Trial?

Incyte Corporation

Lead Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

Findings from Research

In a survey of 1377 allogeneic hematopoietic cell transplant survivors, those with moderate to severe chronic graft-versus-host disease reported significantly worse quality of life and higher symptom burden compared to those whose condition had resolved or who never had it.

A notable percentage (26.7-39.4%) of patients with active chronic graft-versus-host disease were unable to work due to health issues, highlighting the need for improved prevention and treatment strategies to enhance survivorship after transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes and health status associated with chronic graft-versus-host disease. Lee, SJ., Onstad, L., Chow, EJ., et al.[2019]

In a phase 2 study involving 36 patients with steroid-refractory chronic graft-versus-host disease (cGVHD), abatacept demonstrated an overall response rate of 58%, with all responders achieving a partial response, indicating its efficacy as a treatment option.

Abatacept was well tolerated, showing few serious infections, and it positively impacted the immune system by reducing levels of inflammatory markers like IL-1α and TNF-α, suggesting it modifies the immune microenvironment in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 clinical trial evaluating abatacept in patients with steroid-refractory chronic graft-versus-host disease. Koshy, AG., Kim, HT., Liegel, J., et al.[2023]

In a study of 15 patients with steroid-refractory chronic graft-versus-host disease, a combination of low doses of alemtuzumab and rituximab resulted in a 100% overall response rate at 30 days, with 67% achieving partial remission and 33% achieving complete remission.

While the treatment showed efficacy, 67% of patients experienced infections as adverse effects, highlighting the need for careful monitoring, although most infections were resolved quickly, except for one case that resulted in death from pneumonia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of subcutaneous low-dose alemtuzumab and rituximab combination therapy for steroid-resistant chronic graft-versus-host disease. Gutiérrez-Aguirre, CH., Cantú-Rodríguez, OG., Borjas-Almaguer, OD., et al.[2021]

Axatilimab, a monoclonal antibody targeting CSF-1R, shows promise in treating chronic graft-versus-host disease (cGVHD) with a 50% overall response rate after 7 treatment cycles in a phase II study involving 23 patients, and an 82% response rate in the first six cycles.

The treatment demonstrated a favorable safety profile, with manageable adverse effects primarily related to on-target CSF-1R inhibition, and no cases of cytomegalovirus reactivation, indicating its potential as a safe option for patients with refractory cGVHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axatilimab for Chronic Graft-Versus-Host Disease After Failure of at Least Two Prior Systemic Therapies: Results of a Phase I/II Study. Kitko, CL., Arora, M., DeFilipp, Z., et al.[2023]

Ruxolitinib, used as a treatment for chronic graft-versus-host disease (GVHD) resistant to other therapies, can cause significant skin reactions, including ulcerative lesions, as seen in an 18-year-old patient with refractory chronic cutaneous GVHD.

After discontinuing ruxolitinib due to suspected drug-related skin ulcers, the lesions fully recovered within four weeks, highlighting the importance of monitoring for adverse effects in patients receiving this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Skin ulcers caused by ruxolitinib in a patient with chronic cutaneous graft-versus-host disease. Aslan Candır, B., Yiğenoğlu, TN., Kızıl Çakar, M., et al.[2022]

In a phase 1 clinical trial involving 16 patients with steroid-refractory chronic graft-versus-host disease (SR-cGVHD), the immunomodulatory drug abatacept was found to be safe and well-tolerated, with no dose-limiting toxicities reported.

Abatacept led to a 44% clinical partial response rate and a significant 51.3% reduction in prednisone usage among responders, indicating its potential as an effective treatment option for SR-cGVHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 clinical trial evaluating abatacept in patients with steroid-refractory chronic graft-versus-host disease. Nahas, MR., Soiffer, RJ., Kim, HT., et al.[2021]

Acute graft-versus-host disease (GVHD) affects about 50% of patients after allogeneic hematopoietic cell transplant, and high-dose systemic steroids are the primary treatment, but many patients experience treatment failure.

Ruxolitinib is the first FDA-approved treatment specifically for steroid-refractory GVHD, and the review highlights various new treatments being studied, categorized by their mechanisms of action, which may offer hope for better management of this serious condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current and Emerging Targeted Therapies for Acute Graft-Versus-Host Disease. Kasikis, S., Etra, A., Levine, JE.[2022]

In a phase 3 trial involving 203 patients with steroid-resistant acute graft-versus-host disease (aGVHD), the addition of mesenchymal stromal cells (MSCs) to standard second-line therapy significantly improved overall response rates at day 28 (82.8% vs. 70.7%) and at day 56 (78.8% vs. 64.6%).

The MSC treatment not only enhanced efficacy but also reduced the incidence of chronic graft-versus-host disease (cGVHD) and drug-related toxicity, with no increase in tumor relapse rates, indicating that MSCs are a safe and effective second-line treatment option for aGVHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mesenchymal stromal cells plus basiliximab, calcineurin inhibitor as treatment of steroid-resistant acute graft-versus-host disease: a multicenter, randomized, phase 3, open-label trial. Zhao, K., Lin, R., Fan, Z., et al.[2022]

In a study of 36 patients with moderate to severe steroid-refractory chronic GvHD, ruxolitinib demonstrated a 59% overall response rate at three months and 62% at six months, indicating its efficacy as a treatment option.

Ruxolitinib was well-tolerated, with no permanent discontinuations due to adverse events, and it significantly reduced the need for steroid doses, highlighting its safety profile in managing chronic GvHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib for chronic steroid-refractory graft versus host disease: a single center experience. Xue, E., Lorentino, F., Pavesi, F., et al.[2021]

References

1. Italy pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes and health status associated with chronic graft-versus-host disease. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Phase 2 clinical trial evaluating abatacept in patients with steroid-refractory chronic graft-versus-host disease. [2023]

3. Italy pubmed.ncbi.nlm.nih.gov

Effectiveness of subcutaneous low-dose alemtuzumab and rituximab combination therapy for steroid-resistant chronic graft-versus-host disease. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Axatilimab for Chronic Graft-Versus-Host Disease After Failure of at Least Two Prior Systemic Therapies: Results of a Phase I/II Study. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Skin ulcers caused by ruxolitinib in a patient with chronic cutaneous graft-versus-host disease. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Phase 1 clinical trial evaluating abatacept in patients with steroid-refractory chronic graft-versus-host disease. [2021]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Current and Emerging Targeted Therapies for Acute Graft-Versus-Host Disease. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Mesenchymal stromal cells plus basiliximab, calcineurin inhibitor as treatment of steroid-resistant acute graft-versus-host disease: a multicenter, randomized, phase 3, open-label trial. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Ruxolitinib for chronic steroid-refractory graft versus host disease: a single center experience. [2021]