A Study to Assess the Safety and Pharmacokinetics of GDC-8264 in Combination With Standard of Care in Participants With Acute Graft-Versus-Host Disease (aGVHD)

Acute Graft-versus-host Disease Clinical Trial

Official title:

A Phase Ib, Open-label, Randomized, Dose-finding, Multicenter Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of GDC-8264 in Combination With Standard of Care in the Treatment of Acute Graft-versus-Host Disease in Patients Who Have Undergone Allogeneic Hematopoietic Stem Cell Transplantation

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05673876
• Other study ID #: GA43861
• Secondary ID: ISRCTN27200385
• Status: Terminated
• Phase: Phase 1
• Start date: April 6, 2023
• Est. completion date: January 15, 2024

Study information

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

Clinical Trial Summary

The primary purpose of the study is to assess the safety and pharmacokinetics (PK) of GDC-8264 in participants with acute graft-versus-host disease (aGVHD).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. completion date: January 15, 2024
• Est. primary completion date: January 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Diagnosis of post-allogeneic hematopoietic stem cell transplantation (HSCT) aGVHD at screening

• Evidence of engraftment post-transplant

• Diagnosis of high-risk aGVHD, per refined Minnesota high-risk aGVHD criteria during screening

• Initiation of treatment with systemic corticosteroids for aGVHD at a dose of prednisone =2 milligrams per kilograms per day (mg/kg/day) by orally (PO) or methylprednisolone =2 mg/kg/day intravenously (or equivalent) in divided doses at diagnosis and up to 3 days prior to or on the same day as initiation of GDC-8264 (Day 1), with no taper planned prior to Day 3

Exclusion Criteria:

• Evidence of relapsed, progressing, or persistent malignancy, or treatment for relapse after transplant, or requirement for rapid immune suppression withdrawal as pre-emergent treatment of early malignancy relapse

• Prior receipt of more than one allogeneic HSCT

• Prior receipt of solid organ transplantation that are target organs for aGVHD (e.g., liver transplant)

• Prior systemic treatment for aGVHD, except for the standard of care corticosteroid treatment initiated as part of this trial

• Diagnosis of chronic GVHD or overlap syndrome

• Uncontrolled active infection (i.e., progressive symptoms related to infection despite treatment, or persistently positive blood cultures despite treatment, or any other evidence of severe sepsis)

• Severe organ dysfunction (e.g., acute liver failure, renal failure requiring dialysis, ventilator support, or vasopressor therapy)

• Initiation or planned use of a marketed small molecule (excluding corticosteroids) or biologic therapy as treatment for aGVHD from the start of screening through the treatment period

Related Conditions & MeSH terms

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

Intervention

Drug:
• GDC-8264
GDC-8264 tablets will be administered as per the schedule specified in the respective arms.

Locations

Country	Name	City	State
Canada	McMaster University Medical Centre	Hamilton	Ontario
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
United States	Massachusetts General Hospital; Harvard Medical School - Gi Unit Grj724	Boston	Massachusetts
United States	City of Hope National Medical Center	Duarte	California
United States	Columbia University Irving Medical Center	New York	New York
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Abramson Cancer Center; Univ of Pennsylvania; PERELMAN CENTER FOR ADVANCED MEDICINE	Philadelphia	Pennsylvania
United States	Mayo Clinic - PPDS	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants with At Least One Adverse Events (AEs) and As per Severity of AEs		Screening up to end of study (up to approximately 3 years)
Primary	Plasma Concentration of GDC-8264		From Day 1 up to Day 57
Secondary	Overall Response Rate (ORR)		Up to Day 29
Secondary	Duration of Response (DOR)		From Day 29 up to end of study (up to approximately 3 years)
Secondary	Percentage of Participants with aGVHD Flares		Baseline up to Day 56
Secondary	Percentage of Participants with Non-relapse Mortality (NRM)		Baseline up to Day 180