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

NCT04539470 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: GA41825
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 8

Brief 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).

Conditions

Acute Graft-versus-host Disease

Outcome Measures

Primary Outcomes (9)

• 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 Outcomes (2)

• 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

Study Arms (3)

Cohort A: Efmarodocokin Alfa Dosage Level 1

EXPERIMENTAL

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

Cohort B: Efmarodocokin Alfa Dosage Level 2

EXPERIMENTAL

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

Cohort C: Efmarodocokin Alfa Dosage Level 3

EXPERIMENTAL

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

Interventions

Efmarodocokin Alfa DRUG

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

Also known as: UTTR1147A, RG7880, RO7021610, IL-22Fc

Cohort A: Efmarodocokin Alfa Dosage Level 1; Cohort B: Efmarodocokin Alfa Dosage Level 2; Cohort C: Efmarodocokin Alfa Dosage Level 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (8)

City of Hope

Duarte, California, 91010, United States

Location

Ronald Reagan UCLA Medical Center

Los Angeles, California, 90095, United States

Location

University of Miami Miller School of Medicine; Clinical Reseach Building

Miami, Florida, 33136, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

University of Kansas Med Ctr; Int med/Allgy/Immun/Rheum

Kansas City, Kansas, 66160-7350, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Study Officials

• Clinical Trials

  Genentech, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2020
• First Posted: September 7, 2020
• Study Start: November 19, 2020
• Primary Completion: February 24, 2023
• Study Completion: February 24, 2023
• Last Updated: April 11, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)