Clinical trial NCT05673876: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acute Graft-versus-host Disease
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2023-01-06
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs)
timeFrame: From signing informed consent form until 28 days after the final dose of GDC-8264 (up to 9 months)
measure: Plasma Concentration of GDC-8264
timeFrame: 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
measure: Maximum Plasma Concentration (Cmax) of GDC-8264
timeFrame: Day 1 and SS visit (any time between Day 4 to Day 28)
measure: Time to Reach Maximum Plasma Concentration (Tmax) of GDC-8264
timeFrame: Day 1 and SS visit (any time between Day 4 to Day 28)
measure: Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC0-24) of GDC-8264
timeFrame: Day 1 and SS visit (any time between Day 4 to Day 28)
measure: Terminal Half-life (T1/2) of GDC-8264
timeFrame: Day 1 and SS visit (any time between Day 4 to Day 28)
measure: Apparent Clearance (CL/F) of GDC-8264
timeFrame: Day 1 and SS visit (any time between Day 4 to Day 28)
measure: Apparent Volume of Distribution (Vz/F) of GDC-8264
timeFrame: Day 1 and SS visit (any time between Day 4 to Day 28)
Secondary outcomes:
measure: Overall Response Rate (ORR) on Day 29
timeFrame: Up to Day 29
measure: Duration of Response (DOR)
timeFrame: From Day 29 up to end of study (up to 9 months)
measure: Percentage of Participants With aGVHD Flares by Day 56
timeFrame: Baseline up to Day 56
measure: Percentage of Participants With Non-relapse Mortality (NRM) by Day 180
timeFrame: Baseline up to Day 180
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: