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

Acute Graft-versus-host Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04539470
• Other study ID #: GA41825
• Status: Completed
• Phase: Phase 1
• Start date: November 19, 2020
• Est. completion date: February 24, 2023

Study information

• Verified date: April 2024
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: February 24, 2023
• Est. primary completion date: February 24, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Graft-versus-host Disease
• Graft vs Host Disease

Intervention

Drug:
• Efmarodocokin Alfa
Efmarodocokin Alfa will be administered intravenously (IV) per the dosage specified in each dose escalation cohort.

Locations

Country	Name	City	State
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	University of Chicago	Chicago	Illinois
United States	City of Hope	Duarte	California
United States	University of Kansas Med Ctr; Int med/Allgy/Immun/Rheum	Kansas City	Kansas
United States	Ronald Reagan UCLA Medical Center	Los Angeles	California
United States	University of Miami Miller School of Medicine; Clinical Reseach Building	Miami	Florida
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Change from Baseline in Respiratory Rate Over Time		From Baseline up to 139 days
Primary	Change from Baseline in Oxygen Saturation Over Time		From Baseline up to 139 days
Primary	Change from Baseline in Pulse Rate Over Time		From Baseline up to 139 days
Primary	Change from Baseline in Systolic Blood Pressure Over Time		From Baseline up to 139 days
Primary	Change from Baseline in Diastolic Blood Pressure Over Time		From Baseline up to 139 days
Primary	Change from Baseline in Body Temperature Over Time		From Baseline up to 139 days
Primary	Number of Participants with Laboratory Abnormalities in Hematology Tests		From Baseline up to 139 days
Primary	Number of Participants with Laboratory Abnormalities in Blood Chemistry Tests		From Baseline up to 139 days
Secondary	Serum Concentration of Efmarodocokin Alfa at Specified Timepoints		At predefined timepoints from Baseline until Day 139
Secondary	Number of Participants with Anti-Drug Antibodies (ADAs) at Baseline and During the Study		At predefined timepoints from Baseline until Day 139