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)

May 16, 2025 updated by: Genentech, Inc.

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

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
7

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • California
      • Duarte, California, United States, 91010
        • City of Hope National Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
    • New York
      • New York, New York, United States, 10029
        • Icahn School Of Medicine At Mount Sinai
      • New York, New York, United States, 10032
        • Columbia University Irving Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: GDC-8264, 35 mg
Participants will receive oral GDC-8264, 35 milligrams (mg), once daily (QD) for 28 days.
Drug: GDC-8264
GDC-8264 tablets will be administered as per the schedule specified in the respective arms.
Experimental: GDC-8264, 75 mg
Participants will receive oral GDC-8264, 75 mg, PO, QD for 28 days.
Drug: GDC-8264
GDC-8264 tablets will be administered as per the schedule specified in the respective arms.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Adverse Events (AEs)
Time Frame: From signing informed consent form until 28 days after the final dose of GDC-8264 (up to 9 months)
An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
From signing informed consent form until 28 days after the final dose of GDC-8264 (up to 9 months)
Plasma Concentration of GDC-8264
Time Frame: Predose, 1.5, 2, 3, 4, 6, 12, and 24 hours post-dose on Days 1 and 4; Predose on Days 8, 15, 22, 29
Plasma concentration of GDC-8264 at specified timepoints was determined.
Predose, 1.5, 2, 3, 4, 6, 12, and 24 hours post-dose on Days 1 and 4; Predose on Days 8, 15, 22, 29
Maximum Plasma Concentration (Cmax) of GDC-8264
Time Frame: Day 1 and SS visit (any time between Day 4 to Day 28)
Steady-state (SS) PK visit was Day 4 if the participant was hospitalized or Day 8 if the participant was an outpatient. If the SS PK visit samples could not be obtained on Day 4/8, the SS PK visit may have occurred on any dosing day between Day 4 and 28.
Day 1 and SS visit (any time between Day 4 to Day 28)
Time to Reach Maximum Plasma Concentration (Tmax) of GDC-8264
Time Frame: Day 1 and SS visit (any time between Day 4 to Day 28)
SS PK visit was Day 4 if the participant was hospitalized or Day 8 if the participant was an outpatient. If the SS PK visit samples could not be obtained on Day 4/8, the SS PK visit may have occurred on any dosing day between Day 4 and 28.
Day 1 and SS visit (any time between Day 4 to Day 28)
Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC0-24) of GDC-8264
Time Frame: Day 1 and SS visit (any time between Day 4 to Day 28)
SS PK visit was Day 4 if the participant was hospitalized or Day 8 if the participant was an outpatient. If the SS PK visit samples could not be obtained on Day 4/8, the SS PK visit may have occurred on any dosing day between Day 4 and 28.
Day 1 and SS visit (any time between Day 4 to Day 28)
Terminal Half-life (T1/2) of GDC-8264
Time Frame: Day 1 and SS visit (any time between Day 4 to Day 28)
SS PK visit was Day 4 if the participant was hospitalized or Day 8 if the participant was an outpatient. If the SS PK visit samples could not be obtained on Day 4/8, the SS PK visit may have occurred on any dosing day between Day 4 and 28.
Day 1 and SS visit (any time between Day 4 to Day 28)
Apparent Clearance (CL/F) of GDC-8264
Time Frame: Day 1 and SS visit (any time between Day 4 to Day 28)
SS PK visit was Day 4 if the participant was hospitalized or Day 8 if the participant was an outpatient. If the SS PK visit samples could not be obtained on Day 4/8, the SS PK visit may have occurred on any dosing day between Day 4 and 28.
Day 1 and SS visit (any time between Day 4 to Day 28)
Apparent Volume of Distribution (Vz/F) of GDC-8264
Time Frame: Day 1 and SS visit (any time between Day 4 to Day 28)
SS PK visit was Day 4 if the participant was hospitalized or Day 8 if the participant was an outpatient. If the SS PK visit samples could not be obtained on Day 4/8, the SS PK visit may have occurred on any dosing day between Day 4 and 28.
Day 1 and SS visit (any time between Day 4 to Day 28)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Overall Response Rate (ORR) on Day 29
Time Frame: Up to Day 29
ORR=percentage of participants with complete response (CR), very good partial response (VGPR), or partial response (PR) as determined by investigator. CR=all target organs evaluated as Mount Sinai Acute GVHD International Consortium (MAGIC) aGVHD Stage 0 [Skin- no GVHD rash; Liver - bilirubin <2 milligrams/decilitres (mg/dL); Upper gastrointestinal (GI) tract - no intermittent nausea, vomiting/anorexia; Lower GI tract - stool output: < 500 mL/day or <3 episodes/day (adults), <10 mL/kilograms (kg)/day or <4 episodes/day]. VGPR=resolution of signs & symptoms i.e. no rash/residual erythematous rash involving < 25% of body surface, without (w/o) bullae; bilirubin <2 mg/dL or <25% of baseline at screening; toleration of food/enteral feeding; predominantly formed stools; no overt GI bleeding/abdominal cramping; no more than occasional nausea/vomiting. PR=improvement in one/more target organs (skin, liver, upper GI tract, lower GI tract) involved with aGVHD symptoms w/o worsening in others.
Up to Day 29
Duration of Response (DOR)
Time Frame: From Day 29 up to end of study (up to 9 months)
DOR was defined astime from response (CR, VGPR or PR) on Day 29 to aGVHD progression from nadir in any organ, new systemic therapy for aGVHD, or death from any cause (whichever occurs first), as determined by the investigator. CR=all target organs evaluated as MAGIC aGVHD Stage 0 [Skin- no GVHD rash; Liver - bilirubin <2 mg/dL; Upper GI tract - no intermittent nausea, vomiting/anorexia; Lower GI tract - stool output: < 500 mL/day or <3 episodes/day (adults), <10 mL/kg/day or <4 episodes/day]. VGPR=resolution of signs & symptoms i.e. no rash or residual erythematous rash involving < 25% of body surface, without bullae; bilirubin <2 mg/dL or <25% of baseline at screening; toleration of food/enteral feeding; predominantly formed stools; no overt GI bleeding or abdominal cramping; no more than occasional nausea or vomiting. PR=improvement in one or more target organs (skin, liver, upper GI tract, lower GI tract) involved with aGVHD symptoms without worsening in others.
From Day 29 up to end of study (up to 9 months)
Percentage of Participants With aGVHD Flares by Day 56
Time Frame: Baseline up to Day 56
aGVHD flare was defined as an increase in aGVHD target organ stage by at least one stage for at least 3 days that requires either addition of a new line of systemic treatment or increase in corticosteroid dose > 0.25 mg/kg/day.
Baseline up to Day 56
Percentage of Participants With Non-relapse Mortality (NRM) by Day 180
Time Frame: Baseline up to Day 180
NRM was defined as any death that occurred after onset of aGVHD that was not attributable to relapse of the underlying primary disease was considered a non-relapse death.
Baseline up to Day 180

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Genentech, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 6, 2023

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 15, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 15, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 21, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 21, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 6, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 28, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 16, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • GA43861
  • ISRCTN27200385 (Other Identifier: ISRCTN (United Kingdom))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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