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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)

Primary Purpose

Acute Graft-versus-host Disease

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
GDC-8264
Sponsored by
Genentech, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Graft-versus-host Disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • City of Hope National Medical CenterRecruiting
  • Massachusetts General Hospital; Harvard Medical School - Gi Unit Grj724Recruiting
  • Mayo Clinic - PPDSRecruiting
  • Icahn School of Medicine at Mount SinaiRecruiting
  • Columbia University Irving Medical CenterRecruiting
  • Abramson Cancer Center; Univ of Pennsylvania; PERELMAN CENTER FOR ADVANCED MEDICINERecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

GDC-8264, 35 mg

GDC-8264, 75 mg

Arm Description

Participants will receive oral GDC-8264, 35 milligrams (mg), once daily (QD) for 28 days.

Participants will receive oral GDC-8264, 75 mg, PO, QD for 28 days.

Outcomes

Primary Outcome Measures

Percentage of Participants with At Least One Adverse Events (AEs) and As per Severity of AEs
Plasma Concentration of GDC-8264

Secondary Outcome Measures

Overall Response Rate (ORR)
Duration of Response (DOR)
Percentage of Participants with aGVHD Flares
Percentage of Participants with Non-relapse Mortality (NRM)

Full Information

First Posted
December 21, 2022
Last Updated
August 16, 2023
Sponsor
Genentech, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05673876
Brief Title
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)
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 6, 2023 (Actual)
Primary Completion Date
December 30, 2025 (Anticipated)
Study Completion Date
December 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genentech, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Graft-versus-host Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
GDC-8264, 35 mg
Arm Type
Experimental
Arm Description
Participants will receive oral GDC-8264, 35 milligrams (mg), once daily (QD) for 28 days.
Arm Title
GDC-8264, 75 mg
Arm Type
Experimental
Arm Description
Participants will receive oral GDC-8264, 75 mg, PO, QD for 28 days.
Intervention Type
Drug
Intervention Name(s)
GDC-8264
Intervention Description
GDC-8264 tablets will be administered as per the schedule specified in the respective arms.
Primary Outcome Measure Information:
Title
Percentage of Participants with At Least One Adverse Events (AEs) and As per Severity of AEs
Time Frame
Screening up to end of study (up to approximately 3 years)
Title
Plasma Concentration of GDC-8264
Time Frame
From Day 1 up to Day 57
Secondary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Time Frame
Up to Day 29
Title
Duration of Response (DOR)
Time Frame
From Day 29 up to end of study (up to approximately 3 years)
Title
Percentage of Participants with aGVHD Flares
Time Frame
Baseline up to Day 56
Title
Percentage of Participants with Non-relapse Mortality (NRM)
Time Frame
Baseline up to Day 180

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Reference Study ID Number: GA43861 https://forpatients.roche.com/
Phone
888-662-6728
Email
global-roche-genentech-trials@gene.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope National Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Individual Site Status
Recruiting
Facility Name
Massachusetts General Hospital; Harvard Medical School - Gi Unit Grj724
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Individual Site Status
Recruiting
Facility Name
Mayo Clinic - PPDS
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Individual Site Status
Recruiting
Facility Name
Icahn School of Medicine at Mount Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Individual Site Status
Recruiting
Facility Name
Columbia University Irving Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Individual Site Status
Recruiting
Facility Name
Abramson Cancer Center; Univ of Pennsylvania; PERELMAN CENTER FOR ADVANCED MEDICINE
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Learn more about this trial

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)

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