GM-CSF for Reversal of Immunoparalysis in Pediatric Sepsis-induced MODS (GRACE-2)

• ClinicalTrials.gov Identifier: NCT05266001
• Recruitment Status: Recruiting
• First Posted: March 4, 2022
• Last Update Posted: February 8, 2023
• Sponsor: Nationwide Children's Hospital
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Information provided by (Responsible Party): Mark Hall, Nationwide Children's Hospital

Tracking Information

• First Submitted Date: February 23, 2022
• First Posted Date: March 4, 2022
• Last Update Posted Date: February 8, 2023
• Actual Study Start Date: June 14, 2022
• Estimated Primary Completion Date: May 31, 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 2, 2022)

Cumulative 28-day Pediatric Logistic Organ Dysfunction (PELOD)-2 score [ Time Frame: 28 days from randomization ]

Cumulative Pediatric Logistic Organ Dysfunction (PELOD)-2 score through 28 days post-randomization. The range of PELOD-2 score for a given day is 0 - 33 with a higher number being worse.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 2, 2022)

• 3-month health-related quality of life [ Time Frame: 3 months post-randomization ]
  Change in Pediatric Quality of Life inventory (PedsQL) score from baseline to 3 months post-randomization. The range of PedsQL scores is from 0 - 100, with higher values corresponding to better quality of life.
• 3-month functional status [ Time Frame: 3 months post-randomization ]
  Change in Functional Status Score from baseline to 3 months post-randomization. The range of possible FSS score for a given subject is 6 - 30 with a higher score indicating worse function.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: GM-CSF for Reversal of Immunoparalysis in Pediatric Sepsis-induced MODS
• Official Title: GM-CSF for Reversal of Immunoparalysis in Pediatric Sepsis-induced MODS
• Brief Summary: The GRACE-2 study is a prospective, multi-center, double-blind, randomized controlled trial of the drug GM-CSF vs placebo in children with sepsis-induced multiple organ dysfunction syndrome (MODS) who have immunoparalysis with mild to moderate inflammation.
• Detailed Description: The GRACE-2 study is a is a prospective, multi-center, double-blind, randomized controlled trial of the drug GM-CSF vs placebo in children with sepsis-induced multiple organ dysfunction syndrome (MODS) who have immunoparalysis with mild to moderate inflammation. Eligible subjects will undergo centralized immunophenotyping on MODS Day 2. Those who are found to have immunoparalysis (a whole blood LPS-induced TNF-alpha production capacity < 200 pg/ml) with mild to moderate inflammation (serum ferritin level < 2000 ng/ml) will be randomized to receive intravenous (IV) GM-CSF at a dose of 125 mcg/m2/day x 7 days or placebo. The primary outcome variable is the cumulative 28-day Pediatric Logistic Organ Dysfunction (PELOD)-2 score. Secondary outcomes include measures of health-related quality of life and function status at 3 months from randomization.
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Prospective, randomized, double-blind, placebo-controlled clinical trial

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

• Condition: Pediatric Sepsis-induced Multiple Organ Dysfunction Syndrome

Intervention

• Drug: GM-CSF
  same as arm/group description
• Other: Placebo
  same as arm/group description

Study Arms

• Active Comparator: GM-CSF
  Intravenous GM-CSF 125 mcg/m2/day x 7 days
  Intervention: Drug: GM-CSF
• Placebo Comparator: Placebo
  Intravenous placebo x 7 days
  Intervention: Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 2, 2022): 400
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 31, 2027
• Estimated Primary Completion Date: May 31, 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• ≥ 40 weeks corrected gestational age to < 18 years; AND
• Admission to the PICU or CICU; AND
• Onset of ≥ 2 new organ dysfunctions within the last 3 calendar days (compared to pre-sepsis baseline) as measured by the modified Proulx criteria; AND
• Documented or suspected infection as the MODS inciting event.

Exclusion Criteria:

• Weight <3kg; OR
• Limitation of care order at the time of screening; OR
• Patients at high likelihood of progression to brain death in opinion of the clinical team; OR
• Moribund condition in which the patient is unlikely to survive the next 48 hours in opinion of the clinical team; OR
• History of myeloid leukemia, myelodysplasia, or autoimmune thrombocytopenia; OR
• Current or prior diagnosis of hemophagocytic lymphohistiocytosis or macrophage activation syndrome; OR
• Peripheral white blood cell count < 1,000 cells/mm3 as the result of myeloablative therapy OR receipt of myeloablative therapy within the previous 14 days; OR
• Known allergy to GM-CSF; OR
• Known pregnancy; OR
• Lactating females; OR
• Receipt of anakinra or GM-CSF within the previous 28 days; OR
• Resolution of MODS by MODS Day 2; OR
• Previous enrollment in the GRACE-2 study.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Day to 17 Years (Child)
• Accepts Healthy Volunteers: No

Contacts

Contact: Mark W Hall, MD; 6147223438; mark.hall@nationwidechildrens.org

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05266001
• Other Study ID Numbers: GRACE-2
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Mark Hall, Nationwide Children's Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: Nationwide Children's Hospital
• Original Study Sponsor: Same as current
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Not Provided
• PRS Account: Nationwide Children's Hospital
• Verification Date: February 2023