Study to Evaluate the Safety and Pharmacokinetics of Efmarodocokin Alfa in Combination With Standard of Care in Participants Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Study Overview
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Brief Summary
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This is a Phase Ib, open-label, multicenter, dose-escalation study to evaluate the safety, tolerability, and pharmacokinetics of Efmarodocokin Alfa and to make a preliminary assessment of activity of Efmarodocokin Alfa in combination with standard-of-care (SOC) in the prevention of acute graft-versus-host disease (aGVHD) in participants undergoing allogeneic hematopoietic stem cell transplantation (HSCT).

Official Title
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A Phase Ib, Open-Label, Dose-Escalation Study to Evaluate the Safety and Pharmacokinetics of Efmarodocokin Alfa in Combination With Standard of Care in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Conditions
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Acute Graft-versus-host Disease

Intervention / Treatment
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* Drug: Efmarodocokin Alfa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eligible for hematopoietic stem cell transplantation (HSCT) Donor meeting human leukocyte antigen (HLA) matching criteria of HLA-matched related or HLA-matched unrelated (HLA-A, HLA-B, HLA-C, and HLA-DRB1, eight out of eight) from either peripheral blood or bone marrow stem cells and meeting donor-eligibility criteria as outlined by the U.S. Food and Drug Administration (FDA) in 21 CFR 1271 (including screening for Zika and SARS-CoV-2 exposure or infection) Planned HLA (HLA-A, HLA-B, HLA-C, and HLA-DRB1)-matched (eight out of eight) related or planned HLA-matched (eight out of eight) unrelated HSCT, from either peripheral blood or bone marrow stem cells, for patients with acute myeloid leukemia (AML) or acute lymphocytic leukemia (ALL) in first complete remission (per institutional criteria) or patients with intermediate or high-risk myelodysplastic syndrome (MDS) Planned myeloablative conditioning regimen per institutional guidelines Planned aGvHD prophylaxis consisting of tacrolimus and methotrexate; in cases of tacrolimus intolerance, cyclosporine or sirolimus may be used as a substitute Exclusion Criteria: Prior receipt of autologous or allogeneic HSCT Diagnosis of myelofibrosis or myelodysplastic/myeloproliferative overlap syndrome Treatment with investigational biologic or non-biologic therapy within 5 drug elimination half-lives (or within 90 days or 30 days, respectively, if half-life is unknown) prior to initiation of study drug Positive hepatitis B virus (HBV) or hepatitis C virus (HCV) serologies History of Grade >1 cervical intraepithelial neoplasia A marked baseline prolongation of QT/QTc interval Risk factors for torsades de pointes Pregnant or breastfeeding Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A: Efmarodocokin Alfa Dosage Level 1<br>Participants undergoing allogeneic hematopoietic stem cell transplantation will receive Efmarodocokin Alfa dosage level 1 in combination with standard of care prophylaxis treatment for acute graft versus-host disease (aGVHD), consisting of tacrolimus plus methotrexate per institutional practices. | Drug: Efmarodocokin Alfa<br>* Efmarodocokin Alfa will be administered intravenously (IV) per the dosage specified in each dose escalation cohort.<br>* Other names: IL-22Fc;|
| Experimental: Cohort B: Efmarodocokin Alfa Dosage Level 2<br>Participants undergoing allogeneic hematopoietic stem cell transplantation will receive Efmarodocokin Alfa dosage level 2 in combination with standard of care prophylaxis treatment for acute graft versus-host disease (aGVHD), consisting of tacrolimus plus methotrexate per institutional practices. | Drug: Efmarodocokin Alfa<br>* Efmarodocokin Alfa will be administered intravenously (IV) per the dosage specified in each dose escalation cohort.<br>* Other names: IL-22Fc;|
| Experimental: Cohort C: Efmarodocokin Alfa Dosage Level 3<br>Participants undergoing allogeneic hematopoietic stem cell transplantation will receive Efmarodocokin Alfa dosage level 3 in combination with standard of care prophylaxis treatment for acute graft versus-host disease (aGVHD), consisting of tacrolimus plus methotrexate per institutional practices. | Drug: Efmarodocokin Alfa<br>* Efmarodocokin Alfa will be administered intravenously (IV) per the dosage specified in each dose escalation cohort.<br>* Other names: IL-22Fc;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events by Severity, According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) |  | From Baseline up to 365 days | 
| Change from Baseline in Respiratory Rate Over Time |  | From Baseline up to 139 days | 
| Change from Baseline in Oxygen Saturation Over Time |  | From Baseline up to 139 days | 
| Change from Baseline in Pulse Rate Over Time |  | From Baseline up to 139 days | 
| Change from Baseline in Systolic Blood Pressure Over Time |  | From Baseline up to 139 days | 
| Change from Baseline in Diastolic Blood Pressure Over Time |  | From Baseline up to 139 days | 
| Change from Baseline in Body Temperature Over Time |  | From Baseline up to 139 days | 
| Number of Participants with Laboratory Abnormalities in Hematology Tests |  | From Baseline up to 139 days | 
| Number of Participants with Laboratory Abnormalities in Blood Chemistry Tests |  | From Baseline up to 139 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Concentration of Efmarodocokin Alfa at Specified Timepoints |  | At predefined timepoints from Baseline until Day 139 | 
| Number of Participants with Anti-Drug Antibodies (ADAs) at Baseline and During the Study |  | At predefined timepoints from Baseline until Day 139 |