A Study of Mavorixafor in Participants With Congenital and Acquired Primary Autoimmune and Idiopathic Chronic Neutropenic Disorders Who Are Experiencing Recurrent and/or Serious Infections

X4 Pharmaceuticals

Status and phase: Enrolling; Phase 3

Conditions: Neutropenia

Treatments: Drug: Placebo; Drug: Mavorixafor

Study type: Interventional

Funder types: Industry

Identifiers

NCT06056297

X4P-001-110

2023-508482-32-00 (EU Trial (CTIS) Number)

Details and patient eligibility

About

The purpose of this study is to demonstrate the efficacy and evaluate the safety and tolerability of mavorixafor in participants with congenital or acquired primary autoimmune and idiopathic chronic neutropenic disorders who are experiencing recurrent and/or serious infections as assessed by demonstrating its clinical benefit and increasing levels of circulating neutrophils.

Full description

All participants will continue their pre-study background therapy, defined as the participant's current treatment regimen. Options include, but are not limited to, granulocyte-colony stimulating factor (G-CSF), immunoglobulin replacement therapy, prophylactic antibiotics, or "watchful waiting".

Enrollment: 150 estimated patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key 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:

  1. Isolated with a permanent (non-cyclic) presentation, for example, elastase, neutrophil expressed (ELANE), colony stimulating factor 3 receptor (CSF3R), C-X-C chemokine receptor 2 (CXCR2), Wiskott-Aldrich syndrome (WAS)
  2. Associated with extra-hematologic manifestations, for example, Barth syndrome, Cohen syndrome, glucose-6-phosphatase catalytic subunit 3 (G6PC3), Kostmann disease
  3. Associated with metabolic disorders, for example, glycogen storage disease 1b (GSD1b)
  4. Shwachman-Diamond syndrome

• Acquired Primary Neutropenia

  1. Chronic idiopathic neutropenia
  2. 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 an ANC <1000 cells/µL during screening (single ANC value from hematology) and confirmed trough mean ANC (mean value of multiple ANC measurements over 6 hours) at baseline visit, with no clinical evidence of systemic 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 the following criteria:

• Infection requiring the use of antibiotics (intravenous [IV]/oral); OR

• 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);

AND for all potential participants:

• Infections considered by the Investigator to be likely related to the potential participant's CN disorder.
• 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.

Key Exclusion Criteria:

• A diagnosis of secondary neutropenia including those due to:

  1. Hypersplenism
  2. Infection
  3. Malignancy
  4. Autoimmune disease, for example, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, graft-versus-host disease, thyroid disease
  5. Nutritional deficiency, for example, vitamin B12, folic acid, copper, caloric malnutrition
  6. Drug-induced cause, for example, chemotherapy, clozapine, antiretrovirals, antibiotics, monoclonal antibodies.

• A diagnosis of any of the following:

  1. Aplastic anemia

  2. Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome

  3. Certain CNs, including but not limited to these classifications are excluded:

     1. Isolated with a cyclic presentation, for example, elastase, neutrophil expressed (ELANE)
     2. 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
     3. Associated with bone marrow failure, for example, Fanconi anemia, Diamond-Blackfan anemia

  4. 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 C-X-C chemokine receptor 4 (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 has taken other investigational drug <30 days prior to the screening visit or 5 half-lives, whichever is longer.

Note: Other protocol-defined inclusion and exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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150 participants in 2 patient groups, including a placebo group

Mavorixafor

Experimental group

Description:

Participants will receive mavorixafor orally once daily starting from Day 1 through Week 52.

Treatment:

Drug: Mavorixafor

Placebo

Placebo Comparator group

Description:

Participants will receive placebo to match mavorixafor orally once daily starting from Day 1 through Week 52.

Treatment:

Drug: Placebo