A Study of the Safety and Efficacy of Prime Editing (PM359) in Participants With p47phox Autosomal Recessive Chronic Granulomatous Disease (CGD )
NCT Number: NCT06559176
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1|PHASE2
Conditions: Chronic Granulomatous Disease|Granulomatous Disease, Chronic
Interventions: BIOLOGICAL: PM359
Sponsor: Prime Medicine, Inc.
Sex: ALL
Age: CHILD, ADULT, OLDER_ADULT
Enrollment: 12
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-09
Completion Date: 2029-10
Locations: : University of California Los Angeles Medical Center, Los Angeles, California, 90027, United States|NIH Clinical Center, Bethesda, Maryland, 20892, United States|The Children's Hospital at Tristar Medical Group/Sarah Cannon Center for Blood Cancers, Nashville, Tennessee, 37203, United States|CHU - Sainte Justine Hospital, Montréal, Quebec, H3T 1C5, Canada

Summary:
This is an open-label, single-arm, multicenter Phase 1/2 study evaluating the safety and efficacy of gene therapy by transplantation of Prime Edited autologous CD34+ stem cells modified ex vivo (PM359) in participants with autosomal recessive Chronic Granulomatous Disease (CGD) caused by mutations in the NCF1 (Neutrophil Cytosolic Factor 1) gene.

Primary Outcome Measures: Safety of administration of PM359, as quantified by frequency of adverse events (AEs) after drug product infusion, Signing of Informed Consent Form (ICF) through Month 12 after PM359 infusion|Percentage of participants with sustained reconstitution of NADPH oxidase activity in neutrophils, At Month 6 and Month 12 after PM359 infusion, as compared to baseline
Secondary Outcome Measures: Frequency of all drug product-related AEs, ≥ Grade 3 AEs, and serious adverse events (SAEs), Signing of ICF through Month 36 following PM359 infusion|Time to neutrophil engraftment, From PM359 infusion through engraftment, typically within 2-3 weeks but assessed up to 36 months|Transplant related mortality, From PM359 infusion, assessed at 100 Days and 1 Year post-PM359 infusion|Overall survival, From PM359 infusion, assessed at 1 Year and 3 Years post-PM359 infusion|Incidence of acute graft-versus-host disease (GvHD), From PM359 infusion through Month 36|Incidence of graft failure or rejection, From PM359 infusion through Month 36|Durability of multi-lineage hematopoietic cell reconstitution, Assessed at 12, 24 and 36 months following PM359 infusion|Percentage of participants with clinical evidence of malignancy, pre-malignancy or myelodysplasia, From PM359 infusion through Month 36|Percentage of participants with sustained reconstitution of NADPH oxidase activity, Assessed at Month 6 and Month 12 after PM359 infusion|Percentage of participants with sustained reconstitution of NADPH oxidase activity, Assessed at Months 3, 18, 24 and 36 after PM359 infusion|Reconstitution of NADPH oxidase activity in peripheral granulocytes, as measured by DHR assay, Months 1, 2, 3, 6, 12, 18, 24, and 36 after PM359 infusion|Frequency of new or worsening severe bacterial or fungal infections requiring anti-microbial therapy, as compared to baseline, From Month 6 following PM359 infusion through Month 36|Frequency of any new or worsening moderate or greater CGD associated infection requiring anti-microbial therapy with confirmed microbiology demonstrating bacterial or fungal origin consistent with CGD-related pathology, as compared to baseline, From Month 6 following PM359 infusion through Month 36|Frequency of autoimmune or inflammatory, non-infectious processes consistent with CGD, with symptom severity moderate or greater, as compared to baseline, From 1 Year following PM359 infusion through Month 36|Resolution of pre-existing active infections (defined as infection present at time of study enrollment and ongoing at time of PM359 infusion) following PM359 infusion, From PM359 infusion until resolution of active infection, assessed up to Month 36|Resolution of pre-existing autoimmune or inflammatory (non-infectious) processes (defined as autoimmune or inflammatory processes present at time of study enrollment and ongoing at time of PM359 infusion) following PM359 infusion, From PM359 infusion until resolution of autoimmune or inflammatory process, assessed up to Month 36