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NCT06056297PHASE3Recruiting

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

Start Date

6/6/2024

Completion Date

11/1/2027

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

Age Range: 12 years to No maximum

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.

Interventions

DRUG

Mavorixafor

DRUG

Placebo

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Conditions

Neutropenia

Locations

Phoenix Children's Hospital

Phoenix, Arizona 85016

United States

UC Irvine

Irvine, California 92697

United States

Orso Health

La Jolla, California 92037

United States

University of California, Los Angeles-UCLA

Los Angeles, California 90095

United States

Orso Health

Torrance, California 90505

United States

University of Southern Florida

St. Petersburg, Florida 33701

United States

Children's Healthcare of Atlanta (CHOA)

Atlanta, Georgia 30322

United States

University of Iowa

Iowa City, Iowa 52242

United States

Boston Children's Cancer Center

Boston, Massachusetts 02143

United States

University of Michigan

Ann Arbor, Michigan 48109

United States

Washington University

St Louis, Missouri 63130

United States

Duke University Medical Center

Durham, North Carolina 27710

United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio 45229

United States

Cleveland Clinic

Cleveland, Ohio 44195

United States

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania 19104

United States

St. Jude Childrens; Research Hospital

Memphis, Tennessee 38105

United States

UT Southwestern Medical Center

Dallas, Texas 75390

United States

Cook Children's Medical Center

Fort Worth, Texas 76104

United States

Texas Children's Hospital/ Baylor College of Medicine

Houston, Texas 77030

United States

Sarah Cannon Research Institute

Woodland, Texas 77380

United States

University of Utah

Salt Lake City, Utah 84112

United States

Froedtert And Medical College Of Wisconsin

Milwaukee, Wisconsin 53226

United States

Hospital El Cruce

Buenos Aires, B1888AAE

Argentina

Instituto de Investigaciones Clínicas Córdoba

Córdoba, X5000AAW

Argentina

Santorio 9 de Julio

San Miguel de Tucumán, T4000IIH

Argentina

Perth Children's Hospital

Nedlands, 6009

Australia

Icon Cancer Centre Southport

Southport, 4215

Australia

Ballarat Oncology And Haematology Services

Wendouree, 3355

Australia

Universitair Ziekenhuis Leuven

Leuven, 3000

Belgium

University of Alberta Hospital

Edmonton, AB T6G 2R3

Canada

BC Children's Hospital

Vancouver, V5Z 4H4

Canada

Fundacion Cardiovascular de Colombia-Instituto del Corazon Florida Blanca

Floridablanca, Santander Department 681003

Colombia

Clinica IMBANACO S.A.S

Cali, 76004

Colombia

Clínica del Country

Chapinero, 0813

Colombia

Hospital Pablo Tobón Uribe

Medellín, 500034

Colombia

The University Hospital Brno

Brno, 62500

Czechia

Motol University Hospital

Prague, 15006

Czechia

Institute of Hematology and Pediatric Oncology - Lyon

Lyon, 69008

France

Hôpital Saint Louis

Paris, 75010

France

Hospital Armand Trousseau Ap-Hp

Paris, 75012

France

Hôpital Necker - Enfants Malade

Paris, 75015

France

Centre Hospitalier Universitaire de Rennes

Rennes, 75033

France

Institut Universitaire de Cancérologie de Toulouse - Oncopôle

Toulouse, 31059

France

LTD "Israeli-Georgian Medical Research Clinic Healthycore"

Tbilisi, 112

Georgia

LEPL The First University Clinic of Tbilisi State Medical University

Tbilisi, 141

Georgia

JSC K. Eristavi National Center of Experimental and Clinical Surgery

Tbilisi, 159

Georgia

LTD Multiprofile Clinic Concilium Medulla

Tbilisi, 186

Georgia

Klinik und Poliklinik fur Kinder- und Jugendmedizin, Universitatsklinikum Carl Gustav Carus an der TU

Dresden, 01307

Germany

Universitaetsklinikum Carl Gustav Carus Tu Dresden

Dresden, 01307

Germany

Hellenic Airforce 251 General Hospital

Athens, 10177

Greece

University General Hospital of Heraklion

Heraklion, 71500

Greece

The Olympion Private General Clinic

Pátrai, 26443

Greece

AHEPA General Hospital of Thessaloniki

Thessaloniki, 54636

Greece

CMC Deli Klinika

Budapest, 1012

Hungary

Semmelweis University

Budapest, 1085

Hungary

Teaching Hospital Markusovszky

Szombathely, 9700

Hungary

Indira Gandhi Institute Of Medical Sciences

Patna, Bihar 800014

India

Nirmal Hospital Private Limited

Surat, Gujarat 395002

India

Pacific Medical College and Hospital

Udaipur, Rajasthan 313001

India

Yashoda Hospital

Hyderabad, Telangana 500084

India

Ruth Rappaport Children's Hospital, Rambam Health Corporation

Haifa, 3109601

Israel

Hadassah University Hospital-ein Kerem

Jerusalem, 9112001

Israel

Schneider Children's Medical Center of Israel

Petah Tikva, 4920235

Israel

The Chaim Sheba Medical Center

Ramat Gan, 5265601

Israel

A. O. U. delle Marche

Torrette, Ancona 60126

Italy

ASST Spedali Civili di Brescia

Brescia, 25121

Italy

IRCCS Instituto G. Gaslini

Genova, 16147

Italy

Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori (IRST) Dino Amadori

Meldola, 47014

Italy

IRCCS San Gerardo Dei Tintori

Monza, 20900

Italy

Bambino Gesu Children's Hospital

Roma, PC 00165

Italy

AOU Città della salute e della scienza di Torino

Torino, 10126

Italy

Hospital Pakar Kanak-Kanak UKM

Kuala Lumpur, 56000

Malaysia

Unidade Local de Saúde da Região de Aveiro

Aveiro, 3810-164

Portugal

Unidade Local de Saude Coimbra - Paediatric Hospital

Coimbra, 3000-602

Portugal

Unidade Local de Saude Coimbra - Quinta dos Vales

Coimbra, 3041-801

Portugal

Unidade Local de Saude Santa Maria

Lisbon, 1649-028

Portugal

Spitalul Clinic Colentina Site 1

Bucharest, 020125

Romania

Spitalul Clinic Colentina Site 2

Bucharest, 020125

Romania

Institutul Clinic Fundeni

Bucharest, 022328

Romania

Institutul Clinic Fundeni

Bucharest, 22328

Romania

Spitalul Clinic Județean de Urgență

Târgu Mureş, 540136

Romania

University Clinical Centre of Serbia

Belgrade, 11000

Serbia

ICO Badalona - Institut Català d'Oncologia

Barcelona, PC 08916

Spain

Hospital Del Mar

Barcelona, PC08003

Spain

Hospital San Pedro De Alcantara

Cáceres, 10003

Spain

Hospital Universitario Reina Sofía

Córdoba, 14004

Spain

Hospital Universitario de Gran Canaria Doctor Negrín

Las Palmas de Gran Canaria, 35010

Spain

Hospital De La Princesa

Madrid, 28006

Spain

Hospital Universitario Infanta Leonor

Madrid, 28031

Spain

Hospital Universitario Fundacion Jimenez Diaz

Madrid, 28040

Spain

Hospital Universitario Marqués de Valdecilla

Santander, 39008

Spain

Hospital Universitario Virgen del Rocio

Seville, 41013

Spain

Hospital Universitario y Politecnico de la Fe

Valencia, 46026

Spain

Inselspital - University Hospital Bern Site 1

Bern, 3010

Switzerland

Inselspital - University Hospital Bern Site 2

Bern, 3010

Switzerland

Ramathibodi Hospital

Bangkok, 10400

Thailand

Siriraj Hospital

Bangkok, 10700

Thailand

Namik Kemal University (Tekirdağ Namık Kemal Üniversitesi)

Tekirdağ, Süleymanpaşa 59030

Turkey (Türkiye)

Dr. Abdurrahman Yurtaslan Ankara Oncology Training And Research Hospital

Ankara, 6000

Turkey (Türkiye)

Ankara University School of Medicine

Ankara, 6620

Turkey (Türkiye)

Uludag University Faculty Of Medicine

Nilufer,

Turkey (Türkiye)

Ondokuz Mayis University Medical Faculty Hospital

Samsun, 55200

Turkey (Türkiye)

Lviv Regional Clinical Diagnostic Centre

Lviv, Oblast 79010

Ukraine

Medical Center Dobrobut-Clinic LLC

Kyiv, 03151

Ukraine

Medical Center Ok Clinic of International Institute of Clinical Research LLC

Kyiv, 2091

Ukraine

Llc Onto-Med

Kyiv, 3022

Ukraine

Communal non-commercial enterprise "Ternopil City Children's Communal Hospital"

Ternopil, 46000

Ukraine

Medical Center The Clinic of Hospodarskyy LLC

Ternopil, 46002

Ukraine

University Hospital of Wales

Cardiff, CF14 4XW

United Kingdom

Cardiff And Vale University Health Board

London, CF14 4XW

United Kingdom

Royal Free London Nhs Foundation Trust Royal Free Hospital

London, NW3 2QG

United Kingdom

King's College Hospital

London, SE5 9RS

United Kingdom

Imperial College Healthcare Nhs Trust - Hammersmith Hospital

London, W12 0HS

United Kingdom

Great Ormond street Hospital for Children NHS Trust

London, WC1N 1DZ

United Kingdom