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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

NCT06056297 · X4 Pharmaceuticals
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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
About this study
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. * 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 Medical Monitor, 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
Enrollment target: 176 participants
Allocation: randomized
Masking: quadruple
Age groups: child, adult, older_adult
Timeline
Starts: 2024-06-06
Estimated completion: 2027-11
Last updated: 2026-04-13
Interventions
Drug: MavorixaforDrug: Placebo
Primary outcomes
  • Co-primary Endpoint: Annualized Infection Rate Based on Infections Adjudicated by Blinded Infection Adjudication Committee (BIAC) During the Treatment Period (Up to 52 Weeks)
  • Co-primary Endpoint: Number of Participants Meeting the Definition of a Positive Absolute Neutrophil Count (ANC) Response (Up to 52 weeks)
Sponsor
X4 Pharmaceuticals · industry
Contacts & investigators
ContactPatient Affairs and Advocacy · contact · clinicaltrialinfo@x4pharma.com · 857-529-5779
InvestigatorVice President Global Head of Clinical Development and Safety · study_director, X4 Pharmaceuticals
All locations (112)
Phoenix Children's HospitalRecruiting
Phoenix, Arizona, United States
UC IrvineRecruiting
Irvine, California, United States
Orso HealthRecruiting
La Jolla, California, United States
University of California, Los Angeles-UCLARecruiting
Los Angeles, California, United States
Orso HealthRecruiting
Torrance, California, United States
University of Southern FloridaRecruiting
St. Petersburg, Florida, United States
Children's Healthcare of Atlanta (CHOA)Recruiting
Atlanta, Georgia, United States
University of IowaRecruiting
Iowa City, Iowa, United States
Boston Children's Cancer CenterRecruiting
Boston, Massachusetts, United States
University of MichiganRecruiting
Ann Arbor, Michigan, United States
Washington UniversityRecruiting
St Louis, Missouri, United States
Duke University Medical CenterRecruiting
Durham, North Carolina, United States
Cincinnati Children's Hospital Medical CenterRecruiting
Cincinnati, Ohio, United States
Cleveland ClinicRecruiting
Cleveland, Ohio, United States
The Children's Hospital of PhiladelphiaRecruiting
Philadelphia, Pennsylvania, United States
St. Jude Childrens; Research HospitalRecruiting
Memphis, Tennessee, United States
UT Southwestern Medical CenterRecruiting
Dallas, Texas, United States
Cook Children's Medical CenterRecruiting
Fort Worth, Texas, United States
Texas Children's Hospital/ Baylor College of MedicineRecruiting
Houston, Texas, United States
Sarah Cannon Research InstituteRecruiting
Woodland, Texas, United States
University of UtahRecruiting
Salt Lake City, Utah, United States
Froedtert And Medical College Of WisconsinRecruiting
Milwaukee, Wisconsin, United States
Hospital El CruceRecruiting
Buenos Aires, Argentina
Instituto de Investigaciones Clínicas CórdobaRecruiting
Córdoba, Argentina
Santorio 9 de JulioRecruiting
San Miguel de Tucumán, Argentina
Perth Children's HospitalRecruiting
Nedlands, Australia
Icon Cancer Centre SouthportRecruiting
Southport, Australia
Ballarat Oncology And Haematology ServicesRecruiting
Wendouree, Australia
University of Alberta HospitalRecruiting
Edmonton, Canada
BC Children's HospitalRecruiting
Vancouver, Canada
Clinica IMBANACO S.A.SRecruiting
Cali, Colombia
Clínica del CountryRecruiting
Chapinero, Colombia
Hospital Pablo Tobón UribeRecruiting
Medellín, Colombia
The University Hospital BrnoRecruiting
Brno, Czechia
Motol University HospitalRecruiting
Prague, Czechia
Institute of Hematology and Pediatric Oncology - LyonRecruiting
Lyon, France
Hôpital Saint LouisRecruiting
Paris, France
Hospital Armand Trousseau Ap-HpRecruiting
Paris, France
Hôpital Necker - Enfants MaladeRecruiting
Paris, France
Centre Hospitalier Universitaire de RennesRecruiting
Rennes, France
Institut Universitaire de Cancérologie de Toulouse - OncopôleRecruiting
Toulouse, France
LTD "Israeli-Georgian Medical Research Clinic Healthycore"Recruiting
Tbilisi, Georgia
LEPL The First University Clinic of Tbilisi State Medical UniversityRecruiting
Tbilisi, Georgia
JSC K. Eristavi National Center of Experimental and Clinical SurgeryRecruiting
Tbilisi, Georgia
LTD Multiprofile Clinic Concilium MedullaRecruiting
Tbilisi, Georgia
Klinik und Poliklinik fur Kinder- und Jugendmedizin, Universitatsklinikum Carl Gustav Carus an der TURecruiting
Dresden, Germany
Universitaetsklinikum Carl Gustav Carus Tu DresdenRecruiting
Dresden, Germany
Hellenic Airforce 251 General HospitalRecruiting
Athens, Greece
University General Hospital of HeraklionRecruiting
Heraklion, Greece
The Olympion Private General ClinicRecruiting
Pátrai, Greece
AHEPA General Hospital of ThessalonikiRecruiting
Thessaloniki, Greece
CMC Deli KlinikaRecruiting
Budapest, Hungary
Semmelweis UniversityRecruiting
Budapest, Hungary
Teaching Hospital MarkusovszkyRecruiting
Szombathely, Hungary
Indira Gandhi Institute Of Medical SciencesWithdrawn
Patna, Bihar, India
Nirmal Hospital Private LimitedWithdrawn
Surat, Gujarat, India
Pacific Medical College and HospitalWithdrawn
Udaipur, Rajasthan, India
Yashoda HospitalActive Not Recruiting
Hyderabad, Telangana, India
Ruth Rappaport Children's Hospital, Rambam Health CorporationRecruiting
Haifa, Israel
Hadassah University Hospital-ein KeremRecruiting
Jerusalem, Israel
Schneider Children's Medical Center of IsraelRecruiting
Petah Tikva, Israel
The Chaim Sheba Medical CenterRecruiting
Ramat Gan, Israel
A. O. U. delle MarcheRecruiting
Torrette, Ancona, Italy
ASST Spedali Civili di BresciaRecruiting
Brescia, Italy
IRCCS Instituto G. GasliniRecruiting
Genova, Italy
Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori (IRST) Dino AmadoriRecruiting
Meldola, Italy
IRCCS San Gerardo Dei TintoriRecruiting
Monza, Italy
Bambino Gesu Children's HospitalRecruiting
Roma, Italy
AOU Città della salute e della scienza di TorinoRecruiting
Torino, Italy
Hospital Pakar Kanak-Kanak UKMRecruiting
Kuala Lumpur, Malaysia
Unidade Local de Saúde da Região de AveiroRecruiting
Aveiro, Portugal
Unidade Local de Saude Coimbra - Paediatric HospitalRecruiting
Coimbra, Portugal
Unidade Local de Saude Coimbra - Quinta dos ValesRecruiting
Coimbra, Portugal
Unidade Local de Saude Santa MariaRecruiting
Lisbon, Portugal
Spitalul Clinic Colentina Site 1Recruiting
Bucharest, Romania
Spitalul Clinic Colentina Site 2Recruiting
Bucharest, Romania
Institutul Clinic FundeniRecruiting
Bucharest, Romania
Institutul Clinic FundeniRecruiting
Bucharest, Romania
Spitalul Clinic Județean de UrgențăRecruiting
Târgu Mureş, Romania
University Clinical Centre of SerbiaRecruiting
Belgrade, Serbia
ICO Badalona - Institut Català d'OncologiaRecruiting
Barcelona, Spain
Hospital Del MarRecruiting
Barcelona, Spain
Hospital San Pedro De AlcantaraRecruiting
Cáceres, Spain
Hospital Universitario Reina SofíaWithdrawn
Córdoba, Spain
Hospital Universitario de Gran Canaria Doctor NegrínRecruiting
Las Palmas de Gran Canaria, Spain
Hospital De La PrincesaRecruiting
Madrid, Spain
Hospital Universitario Infanta LeonorWithdrawn
Madrid, Spain
Hospital Universitario Fundacion Jimenez DiazRecruiting
Madrid, Spain
Hospital Universitario Marqués de ValdecillaRecruiting
Santander, Spain
Hospital Universitario Virgen del RocioRecruiting
Seville, Spain
Hospital Universitario y Politecnico de la FeRecruiting
Valencia, Spain
Inselspital - University Hospital Bern Site 1Recruiting
Bern, Switzerland
Inselspital - University Hospital Bern Site 2Recruiting
Bern, Switzerland
Ramathibodi HospitalRecruiting
Bangkok, Thailand
Siriraj HospitalRecruiting
Bangkok, Thailand
Namik Kemal University (Tekirdağ Namık Kemal Üniversitesi)Recruiting
Tekirdağ, Süleymanpaşa, Turkey (Türkiye)
Dr. Abdurrahman Yurtaslan Ankara Oncology Training And Research HospitalRecruiting
Ankara, Turkey (Türkiye)
Ankara University School of MedicineRecruiting
Ankara, Turkey (Türkiye)
Uludag University Faculty Of MedicineRecruiting
Nilufer, Turkey (Türkiye)
Ondokuz Mayis University Medical Faculty HospitalRecruiting
Samsun, Turkey (Türkiye)
Lviv Regional Clinical Diagnostic CentreRecruiting
Lviv, Oblast, Ukraine
Medical Center Dobrobut-Clinic LLCRecruiting
Kyiv, Ukraine
Medical Center Ok Clinic of International Institute of Clinical Research LLCRecruiting
Kyiv, Ukraine
Llc Onto-MedRecruiting
Kyiv, Ukraine
Communal non-commercial enterprise "Ternopil City Children's Communal Hospital"Recruiting
Ternopil, Ukraine
Medical Center The Clinic of Hospodarskyy LLCRecruiting
Ternopil, Ukraine
University Hospital of WalesRecruiting
Cardiff, United Kingdom
Cardiff And Vale University Health BoardRecruiting
London, United Kingdom
Royal Free London Nhs Foundation Trust Royal Free HospitalRecruiting
London, United Kingdom
King's College HospitalRecruiting
London, United Kingdom
Imperial College Healthcare Nhs Trust - Hammersmith HospitalRecruiting
London, United Kingdom
Great Ormond street Hospital for Children NHS TrustRecruiting
London, United Kingdom
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 · TrialPath