Clinical trial NCT06056297: 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
Official title: A Phase 3, Randomized, Double-blind, Placebo-controlled, Multicenter Study of Mavorixafor in Participants With Congenital and Acquired Primary Autoimmune and Idiopathic Chronic Neutropenic Disorders Who Are Experiencing Recurrent and/or Serious Infections
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Neutropenia
Keywords: Mavorixafor
Chronic neutropenia
Chronic idiopathic neutropenia
Severe Congenital Neutropenia (SCN)
C-X-C chemokine receptor 4 (CXCR4)
Congenital and acquired neutropenia
Autoimmune disease
Cohen syndrome
Barth syndrome
ELANE
G6PC3
GSD1b
Kostmann disease
Shwachman-Diamond syndrome
Autoimmune neutropenia (AIN)
Lead sponsor: X4 Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2023-09-28
Enrollment: 150
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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".

Eligibility 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.

Primary outcomes:
measure: Annualized Infection Rate Based on Infections Adjudicated by Blinded Infection Adjudication Committee (BIAC) During the Treatment Period
timeFrame: Up to 52 Weeks
measure: Number of Participants Meeting the Definition of a Positive Absolute Neutrophil Count (ANC) Response
timeFrame: Up to 52 weeks
Secondary outcomes:
measure: Infection Severity Based on Common Terminology Criteria for Adverse Events (CTCAE) Adjudicated by a BIAC During the Treatment Period
timeFrame: Up to 52 Weeks
measure: Infection Duration Based on Duration of Infections Adjudicated by a BIAC During the Treatment Period in Those Participants who Developed Infections
timeFrame: Up to 52 Weeks
measure: Antibiotic Use Due to Infection, Characterized by the Frequency of Antibiotic Use During the Treatment Period
timeFrame: Up to 52 Weeks
measure: Oral Ulcers, as Assessed by Presence or Absence of Ulcers During the Treatment Period
timeFrame: Up to 52 Weeks
measure: Change From Baseline in Patient Reported Outcomes Measurement Information System Short Form (PROMIS SF) Fatigue Questionnaire Total Score
timeFrame: Baseline, Week 52
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: La Jolla
country: United States
facility: Orso Health
state: California
city: Torrance
country: United States
facility: Orso Health
state: California
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: Córdoba
country: Argentina
facility: Instituto de Investigaciones Clínicas Córdoba
city: San Miguel de Tucumán
country: Argentina
facility: Santorio 9 de Julio
city: Southport
country: Australia
facility: Icon Cancer Centre Southport
city: Edmonton
country: Canada
facility: University of Alberta Hospital
city: Brno
country: Czechia
facility: The University Hospital Brno
city: Prague
country: Czechia
facility: Motol University Hospital
city: Lyon
country: France
facility: Institute of Hematology and Pediatric Oncology - Lyon
city: Paris
country: France
facility: Hôpital Saint Louis
city: Paris
country: France
facility: Hospital Armand Trousseau Ap-Hp
city: Paris
country: France
facility: Hôpital Necker - Enfants Malade
city: Rennes
country: France
facility: Centre Hospitalier Universitaire de Rennes
city: Tbilisi
country: Georgia
facility: LTD "Israeli-Georgian Medical Research Clinic Healthycore"
city: Tbilisi
country: Georgia
facility: LEPL The First University Clinic of Tbilisi State Medical University
city: Tbilisi
country: Georgia
facility: JSC K. Eristavi National Center of Experimental and Clinical Surgery
city: Tbilisi
country: Georgia
facility: LTD Multiprofile Clinic Concilium Medulla
city: Dresden
country: Germany
facility: Klinik und Poliklinik fur Kinder- und Jugendmedizin, Universitatsklinikum Carl Gustav Carus an der TU
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus Tu Dresden
city: Athens
country: Greece
facility: Hellenic Airforce 251 General Hospital
city: Iraklio
country: Greece
facility: University General Hospital of Heraklion
city: Patra
country: Greece
facility: The Olympion Private General Clinic
city: Thessaloniki
country: Greece
facility: AHEPA General Hospital of Thessaloniki
city: Budapest
country: Hungary
facility: CMC Deli Klinika
city: Budapest
country: Hungary
facility: Semmelweis University
city: Szombathely
country: Hungary
facility: Teaching Hospital Markusovszky
city: Patna
country: India
facility: Indira Gandhi Institute Of Medical Sciences
state: Bihar
city: Surat
country: India
facility: Nirmal Hospital Private Limited
state: Gujarat
city: Udaipur
country: India
facility: Pacific Medical College and Hospital
state: Rajasthan
city: Hyderabad
country: India
facility: Yashoda Hospital
state: Telangana
city: Haifa
country: Israel
facility: Ruth Rappaport Children's Hospital, Rambam Health Corporation
city: Torrette
country: Italy
facility: A. O. U. delle Marche
state: Ancona
city: Brescia
country: Italy
facility: ASST Spedali Civili di Brescia
city: Genova
country: Italy
facility: IRCCS Instituto G. Gaslini
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori (IRST) Dino Amadori
city: Monza
country: Italy
facility: IRCCS San Gerardo Dei Tintori
city: Aveiro
country: Portugal
facility: Unidade Local de Saúde da Região de Aveiro
city: Coimbra
country: Portugal
facility: Unidade Local de Saude Coimbra - Paediatric Hospital
city: Coimbra
country: Portugal
facility: Unidade Local de Saude Coimbra - Quinta dos Vales
city: Bucharest
country: Romania
facility: Spitalul Clinic Colentina Site 1
city: Bucharest
country: Romania
facility: Spitalul Clinic Colentina Site 2
city: Bucharest
country: Romania
facility: Institutul Clinic Fundeni
city: Bucharest
country: Romania
facility: Institutul Clinic Fundeni
city: Târgu-Mureş
country: Romania
facility: Spitalul Clinic Județean de Urgență
city: Belgrade
country: Serbia
facility: University Clinical Centre of Serbia
city: Barcelona
country: Spain
facility: ICO Badalona - Institut Català d'Oncologia
city: Barcelona
country: Spain
facility: Hospital Del Mar
city: Cáceres
country: Spain
facility: Hospital San Pedro De Alcantara
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofía
city: Madrid
country: Spain
facility: Hospital De La Princesa
city: Madrid
country: Spain
facility: Hospital Universitario Infanta Leonor
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Bern
country: Switzerland
facility: Inselspital - University Hospital Bern Site 1
city: Bern
country: Switzerland
facility: Inselspital - University Hospital Bern Site 2
city: Bangkok
country: Thailand
facility: Ramathibodi Hospital
city: Bangkok
country: Thailand
facility: Siriraj Hospital
city: Ankara
country: Turkey
facility: Dr. Abdurrahman Yurtaslan Ankara Oncology Training And Research Hospital
city: Ankara
country: Turkey
facility: Ankara University School of Medicine
city: Nilufer
country: Turkey
facility: Uludag University Faculty Of Medicine
city: Samsun
country: Turkey
facility: Ondokuz Mayis University Medical Faculty Hospital
city: Lviv
country: Ukraine
facility: Lviv Regional Clinical Diagnostic Centre
state: Oblast
city: Kyiv
country: Ukraine
facility: Medical Center Dobrobut-Clinic LLC
city: Kyiv
country: Ukraine
facility: Medical Center Ok Clinic of International Institute of Clinical Research LLC
city: Kyiv
country: Ukraine
facility: Llc Onto-Med
city: Ternopil
country: Ukraine
facility: Communal non-commercial enterprise "Ternopil City Children's Communal Hospital"
city: Ternopil
country: Ukraine
facility: Medical Center The Clinic of Hospodarskyy LLC
city: London
country: United Kingdom
facility: Cardiff And Vale University Health Board
city: London
country: United Kingdom
facility: Royal Free London Nhs Foundation Trust Royal Free Hospital
city: London
country: United Kingdom
facility: King's College Hospital
city: London
country: United Kingdom
facility: Imperial College Healthcare Nhs Trust - Hammersmith Hospital
city: London
country: United Kingdom
facility: Great Ormond street Hospital for Children NHS Trust
Study officials:
affiliation: X4 Pharmaceuticals
name: Chief Medical Officer
role: STUDY_DIRECTOR
References: