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

• Sponsor: Genentech, Inc. (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT04539470
• Collaborator: (none)
• Enrollment: 18
• Locations: 8
• Arms: 3
• Anticipated Duration (Months): 27.6
• Patients Per Site: 2.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Acute Graft-versus-host Disease	Drug: Efmarodocokin Alfa	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• 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
• Actual Study Start Date: Nov 19, 2020
• Anticipated Primary Completion Date: Mar 8, 2023
• Anticipated Study Completion Date: Mar 8, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort A: Efmarodocokin Alfa Dosage Level 1 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; Efmarodocokin Alfa will be administered intravenously (IV) per the dosage specified in each dose escalation cohort.; Other Names: UTTR1147A RG7880 RO7021610 IL-22Fc
Experimental: Cohort B: Efmarodocokin Alfa Dosage Level 2 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; Efmarodocokin Alfa will be administered intravenously (IV) per the dosage specified in each dose escalation cohort.; Other Names: UTTR1147A RG7880 RO7021610 IL-22Fc
Experimental: Cohort C: Efmarodocokin Alfa Dosage Level 3 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; Efmarodocokin Alfa will be administered intravenously (IV) per the dosage specified in each dose escalation cohort.; Other Names: UTTR1147A RG7880 RO7021610 IL-22Fc

Outcome Measures

Primary Outcome Measures

1. 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]

2. Change from Baseline in Respiratory Rate Over Time [From Baseline up to 139 days]

3. Change from Baseline in Oxygen Saturation Over Time [From Baseline up to 139 days]

4. Change from Baseline in Pulse Rate Over Time [From Baseline up to 139 days]

5. Change from Baseline in Systolic Blood Pressure Over Time [From Baseline up to 139 days]

6. Change from Baseline in Diastolic Blood Pressure Over Time [From Baseline up to 139 days]

7. Change from Baseline in Body Temperature Over Time [From Baseline up to 139 days]

8. Number of Participants with Laboratory Abnormalities in Hematology Tests [From Baseline up to 139 days]

9. Number of Participants with Laboratory Abnormalities in Blood Chemistry Tests [From Baseline up to 139 days]

Secondary Outcome Measures

1. Serum Concentration of Efmarodocokin Alfa at Specified Timepoints [At predefined timepoints from Baseline until Day 139]

2. Number of Participants with Anti-Drug Antibodies (ADAs) at Baseline and During the Study [At predefined timepoints from Baseline until Day 139]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope	Duarte	California	United States	91010
2	Ronald Reagan UCLA Medical Center	Los Angeles	California	United States	90095
3	University of Miami Miller School of Medicine; Clinical Reseach Building	Miami	Florida	United States	33136
4	University of Chicago	Chicago	Illinois	United States	60637
5	University of Kansas Med Ctr; Int med/Allgy/Immun/Rheum	Kansas City	Kansas	United States	66160-7350
6	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
7	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
8	Roswell Park Cancer Institute	Buffalo	New York	United States	14263

Sponsors and Collaborators

• Genentech, Inc.

Investigators

• Study Director: Clinical Trials, Genentech, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Genentech, Inc.
• ClinicalTrials.gov Identifier: NCT04539470
• Other Study ID Numbers: GA41825
• First Posted: Sep 7, 2020
• Last Update Posted: Jun 21, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Graft vs Host Disease

Study Results

No Results Posted as of Jun 21, 2022