Clinical Trial: 4WARD Study for Chronic Neutropenia

Autoimmune Neutropenia

The 4WARD Study is a phase 3, randomized, double-blind, placebo controlled, multicenter study of mavorixafor in participants with congenital and acquired primary autoimmune and idiopathic chronic neutropenia disorders who are experiencing recurrent and/or serious infections.

Inclusion Criteria:

• Diagnosis of congenital or acquired primary autoimmune and idiopathic chronic neutropenic disorder ≥6 months prior to the screening visit that is not attributable to medications, active or recent infections or malignancy.
• Congenital Neutropenia, including but not limited to these classifications:
  • Isolated with a permanent (non-cyclic) presentation, for example, ELANE, CSF3R, CXCR2, WAS
  • Associated with extra-hematological manifestations, for example, Barth syndrome, Cohen syndrome, G6PC3, Kostmann disease
  • Associated with metabolic disorders, for example, glycogen storage disease 1b (GSD1b)
  • Shwachman-Diamond syndrome
• Acquired Primary Neutropeni
  • Chronic idiopathic neutropenia
  • Primary autoimmune neutropenia. Other chronic neutropenia (CN) disorders that may be eligible for enrollment can be clarified and approved upon discussion with Study Medical Monitor and Sponsor.
• Have a confirmed trough ANC <1500 cells/µL during the screening visit (single ANC measurement) and at baseline visit (mean ANC over 6 hours) held at least 2 weeks prior to Day 1 dosing, with no clinical evidence of infection.
• Prior history of recurrent and/or serious infections during the 12 months preceding the screening visit (that is, suffering sequelae of chronic neutropenia), as defined by having at least 2 infections in the last 12 months that meet at least 1 of the following criteria:
• Infection requiring the use of antibiotics (intravenous [IV]/oral/topical)
• Infection requiring a visit to healthcare facility (including but not limited to emergency room visit, urgent care facility, primary care physician’s office, or in-patient hospitalization)
• Participants who are on G-CSF or other active background therapy must have been receiving these therapies during the previous 12 months while continuing to suffer from infections, be on a stable dose and dosing schedule for ≥4 weeks prior to screening visit and remain on this dose and dosing schedule throughout the study (unless ANC >10,000 cells/µL for ≥4 weeks).
• Participants must be willing to keep their G-CSF or other background therapy doses/regimens stable (other than for safety reasons) for the duration of the study

Exclusion Criteria:

• A diagnosis of secondary neutropenia including those due to:
  •  Hypersplenism
  • Infection
  • Malignancy
  • Autoimmune disease, for example, systemic lupus erythematosus, rheumatoid arthritis, irritable bowel disease, graft-versus-host disease, thyroid disease
  • Nutritional deficiency, for example, vitamin B12, folic acid, copper, caloric malnutrition
  • Drug-induced cause, for example, chemotherapy, clozapine, antiretrovirals, antibiotics, monoclonal antibodies.
• A diagnosis of any of the following:
  • Aplastic anemia
  • Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome
  • Certain CNs, including but not limited to these classifications are excluded:
    • Isolated with a cyclic presentation, for example, elastase, neutrophil expressed (ELANE)
    • Associated with immune dysregulation, for example, common variable immunodeficiency (CVID), autoimmune lymphoproliferative syndrome (ALPS), familial hemophagocytic lymphohistiocytosis, Chédiak-Higashi syndrome, GATA-binding protein 2 (GATA2) deficiency syndrome
    • Associated with bone marrow failure, for example, Fanconi anemia, Diamond-Blackfan anemia
  • Neutropenia associated with a Duffy-null phenotype (formerly known as benign ethnic neutropenia). However, a participant with an autosomal dominant pathogenic variant in a gene associated with CN on a Duffy-null background may be eligible for inclusion
• A medical or personal condition that may potentially compromise the safety of the participant, may preclude the participant’s successful completion of the clinical study, or could, in the opinion of the Investigator or the Sponsor, interfere with the objectives of the study.
• Received more than 1 dose of mavorixafor in the past.
• Received CXCR4 antagonist (other than mavorixafor) in the past 6 months.
• Participants taking pegylated-G-CSF unless they have a diagnosis of congenital neutropenia confirmed at screening.
• Participant is currently taking or have taken other investigational drug at least 30 days prior to the screening visit.

Please click here to see if you qualify, and to learn more and sign up to meet with the study nurse. For questions, email [email protected] or call 857-529-5779.