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

Phase 3

Recruiting

• Conditions: Neutropenia
• Interventions: Drug: Mavorixafor; Drug: Placebo

• Registration Number: NCT06056297
• Lead Sponsor: X4 Pharmaceuticals

Brief Summary

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.

Detailed 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".

Study Timeline

• Study First Submitted: 2023-09-20
• Study First Submitted QC: 2023-09-20
• Study First Posted: 2023-09-28
• Study Start: 2024-06-06
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-14
• Last Update Posted: 2025-04-17
• Primary Completion: 2026-07
• Study Completion: 2026-08

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 150

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Mavorixafor	Mavorixafor	Participants will receive mavorixafor orally once daily starting from Day 1 through Week 52.
Placebo	Placebo	Participants will receive placebo to match mavorixafor orally once daily starting from Day 1 through Week 52.

Primary Outcome Measures

Name	Time	Method
Annualized Infection Rate Based on Infections Adjudicated by Blinded Infection Adjudication Committee (BIAC) During the Treatment Period	Up to 52 Weeks
Number of Participants Meeting the Definition of a Positive Absolute Neutrophil Count (ANC) Response	Up to 52 weeks	Positive ANC response: Increase of ANC \>500 cells/microliter (µL) from baseline.

Secondary Outcome Measures

Name	Time	Method
Infection Severity Based on Common Terminology Criteria for Adverse Events (CTCAE) Adjudicated by a BIAC During the Treatment Period	Up to 52 Weeks
Infection Duration Based on Duration of Infections Adjudicated by a BIAC During the Treatment Period in Those Participants who Developed Infections	Up to 52 Weeks
Antibiotic Use Due to Infection, Characterized by the Frequency of Antibiotic Use During the Treatment Period	Up to 52 Weeks
Oral Ulcers, as Assessed by Presence or Absence of Ulcers During the Treatment Period	Up to 52 Weeks
Change From Baseline in Patient Reported Outcomes Measurement Information System Short Form (PROMIS SF) Fatigue Questionnaire Total Score	Baseline, Week 52

Trial Locations

Locations (78)

Universitaetsklinikum Carl Gustav Carus Tu Dresden; 🇩🇪 Dresden, Germany

Hellenic Airforce 251 General Hospital; 🇬🇷 Athens, Greece

University General Hospital of Heraklion; 🇬🇷 Iraklio, Greece

The Olympion Private General Clinic; 🇬🇷 Patra, Greece

AHEPA General Hospital of Thessaloniki; 🇬🇷 Thessaloniki, Greece

CMC Deli Klinika; 🇭🇺 Budapest, Hungary

Semmelweis University; 🇭🇺 Budapest, Hungary

Teaching Hospital Markusovszky; 🇭🇺 Szombathely, Hungary

Indira Gandhi Institute Of Medical Sciences; 🇮🇳 Patna, Bihar, India

Nirmal Hospital Private Limited; 🇮🇳 Surat, Gujarat, India

Pacific Medical College and Hospital; 🇮🇳 Udaipur, Rajasthan, India

Yashoda Hospital; 🇮🇳 Hyderabad, Telangana, India

Ruth Rappaport Children's Hospital, Rambam Health Corporation; 🇮🇱 Haifa, Israel

A. O. U. delle Marche; 🇮🇹 Torrette, Ancona, Italy

ASST Spedali Civili di Brescia; 🇮🇹 Brescia, Italy

IRCCS Instituto G. Gaslini; 🇮🇹 Genova, Italy

Medical Center Dobrobut-Clinic LLC; 🇺🇦 Kyiv, Ukraine

Phoenix Children's Hospital; 🇺🇸 Phoenix, Arizona, United States

Orso Health; 🇺🇸 Torrance, California, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Washington University; 🇺🇸 Saint Louis, Missouri, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States

Cincinnati Children's Hospital Medical Center; 🇺🇸 Cincinnati, Ohio, United States

UT Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States

Cook Children's Medical Center; 🇺🇸 Fort Worth, Texas, United States

Instituto de Investigaciones Clínicas Córdoba; 🇦🇷 Córdoba, Argentina

Santorio 9 de Julio; 🇦🇷 San Miguel de Tucumán, Argentina

Icon Cancer Centre Southport; 🇦🇺 Southport, Australia

University of Alberta Hospital; 🇨🇦 Edmonton, Canada

The University Hospital Brno; 🇨🇿 Brno, Czechia

Motol University Hospital; 🇨🇿 Prague, Czechia

Institute of Hematology and Pediatric Oncology - Lyon; 🇫🇷 Lyon, France

Hôpital Saint Louis; 🇫🇷 Paris, France

Hospital Armand Trousseau Ap-Hp; 🇫🇷 Paris, France

Hôpital Necker - Enfants Malade; 🇫🇷 Paris, France

Centre Hospitalier Universitaire de Rennes; 🇫🇷 Rennes, France

LTD "Israeli-Georgian Medical Research Clinic Healthycore"; 🇬🇪 Tbilisi, Georgia

LEPL The First University Clinic of Tbilisi State Medical University; 🇬🇪 Tbilisi, Georgia

JSC K. Eristavi National Center of Experimental and Clinical Surgery; 🇬🇪 Tbilisi, Georgia

LTD Multiprofile Clinic Concilium Medulla; 🇬🇪 Tbilisi, Georgia

Klinik und Poliklinik fur Kinder- und Jugendmedizin, Universitatsklinikum Carl Gustav Carus an der TU; 🇩🇪 Dresden, Germany

Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori (IRST) Dino Amadori; 🇮🇹 Meldola, Italy

IRCCS San Gerardo Dei Tintori; 🇮🇹 Monza, Italy

Unidade Local de Saúde da Região de Aveiro; 🇵🇹 Aveiro, Portugal

Unidade Local de Saude Coimbra - Paediatric Hospital; 🇵🇹 Coimbra, Portugal

Unidade Local de Saude Coimbra - Quinta dos Vales; 🇵🇹 Coimbra, Portugal

Spitalul Clinic Colentina Site 1; 🇷🇴 Bucharest, Romania

Institutul Clinic Fundeni; 🇷🇴 Bucharest, Romania

Spitalul Clinic Colentina Site 2; 🇷🇴 Bucharest, Romania

Spitalul Clinic Județean de Urgență; 🇷🇴 Târgu-Mureş, Romania

University Clinical Centre of Serbia; 🇷🇸 Belgrade, Serbia

ICO Badalona - Institut Català d'Oncologia; 🇪🇸 Barcelona, Spain

Hospital Del Mar; 🇪🇸 Barcelona, Spain

Hospital San Pedro De Alcantara; 🇪🇸 Cáceres, Spain

Hospital Universitario Reina Sofía; 🇪🇸 Córdoba, Spain

Hospital De La Princesa; 🇪🇸 Madrid, Spain

Hospital Universitario Infanta Leonor; 🇪🇸 Madrid, Spain

Hospital Universitario Fundacion Jimenez Diaz; 🇪🇸 Madrid, Spain

Hospital Universitario Marqués de Valdecilla; 🇪🇸 Santander, Spain

Hospital Universitario Virgen del Rocio; 🇪🇸 Sevilla, Spain

Inselspital - University Hospital Bern Site 1; 🇨🇭 Bern, Switzerland

Inselspital - University Hospital Bern Site 2; 🇨🇭 Bern, Switzerland

Ramathibodi Hospital; 🇹🇭 Bangkok, Thailand

Siriraj Hospital; 🇹🇭 Bangkok, Thailand

Dr. Abdurrahman Yurtaslan Ankara Oncology Training And Research Hospital; 🇹🇷 Ankara, Turkey

Ankara University School of Medicine; 🇹🇷 Ankara, Turkey

Uludag University Faculty Of Medicine; 🇹🇷 Nilufer, Turkey

Ondokuz Mayis University Medical Faculty Hospital; 🇹🇷 Samsun, Turkey

Lviv Regional Clinical Diagnostic Centre; 🇺🇦 Lviv, Oblast, Ukraine

Medical Center Ok Clinic of International Institute of Clinical Research LLC; 🇺🇦 Kyiv, Ukraine

Llc Onto-Med; 🇺🇦 Kyiv, Ukraine

Communal non-commercial enterprise "Ternopil City Children's Communal Hospital"; 🇺🇦 Ternopil, Ukraine

Medical Center The Clinic of Hospodarskyy LLC; 🇺🇦 Ternopil, Ukraine

Cardiff And Vale University Health Board; 🇬🇧 London, United Kingdom

Royal Free London Nhs Foundation Trust Royal Free Hospital; 🇬🇧 London, United Kingdom

King's College Hospital; 🇬🇧 London, United Kingdom

Imperial College Healthcare Nhs Trust - Hammersmith Hospital; 🇬🇧 London, United Kingdom

Great Ormond street Hospital for Children NHS Trust; 🇬🇧 London, United Kingdom