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

Официальное название

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

Обзор

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.

Подробное описание

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".

Вмешательства

• Препарат Mavorixafor
  Mavorixafor will be administered per schedule specified in the arm description.
• Препарат Placebo
  Placebo will be administered per schedule specified in the arm description.

Первичные конечные точки

• Co-primary Endpoint: Annualized Infection Rate Based on Infections Adjudicated by Blinded Infection Adjudication Committee (BIAC) During the Treatment Period [Срок оценки: Up to 52 Weeks]
• Co-primary Endpoint: Number of Participants Meeting the Definition of a Positive Absolute Neutrophil Count (ANC) Response [Срок оценки: Up to 52 weeks]

Вторичные конечные точки (5)

• Infection Severity Based on Common Terminology Criteria for Adverse Events (CTCAE) Adjudicated by a BIAC During the Treatment Period [Срок оценки: 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 [Срок оценки: Up to 52 Weeks]
• Antibiotic Use Due to Infection, Characterized by the Frequency of Antibiotic Use During the Treatment Period [Срок оценки: Up to 52 Weeks]
• Oral Ulcers, as Assessed by Presence or Absence of Ulcers During the Treatment Period [Срок оценки: Up to 52 Weeks]
• Change From Baseline in Patient Reported Outcomes Measurement Information System Short Form (PROMIS SF) Fatigue Questionnaire Total Score [Срок оценки: Baseline, Week 52]

Критерии участия

Критерии включения

• 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:

• 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)
• Associated with extra-hematologic manifestations, for example, Barth syndrome, Cohen syndrome, glucose-6-phosphatase catalytic subunit 3 (G6PC3), Kostmann disease
• Associated with metabolic disorders, for example, glycogen storage disease 1b (GSD1b)
• Shwachman-Diamond syndrome
• Acquired Primary Neutropenia

• Chronic idiopathic neutropenia
• 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.

Критерии исключения

• A diagnosis of secondary neutropenia including those due to:

• Hypersplenism
• Infection
• Malignancy
• Autoimmune disease, for example, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, graft-versus-host disease, thyroid disease
• Nutritional deficiency, for example, vitamin B12, folic acid, copper, caloric malnutrition
• Drug-induced cause, for example, chemotherapy, clozapine, antiretrovirals, antibiotics, monoclonal antibodies.
• A diagnosis of any of the following:

• Aplastic anemia
• Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome
• Certain CNs, including but not limited to these classifications are excluded:

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 22 центра

• Phoenix Children's Hospital — Phoenix
• UC Irvine — Irvine
• Orso Health — La Jolla
• University of California, Los Angeles-UCLA — Los Angeles
• Orso Health — Torrance
• University of Southern Florida — St. Petersburg
• Children's Healthcare of Atlanta (CHOA) — Atlanta
• University of Iowa — Iowa City
• … и ещё 14 центров

Испания · 11 центров

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Италия · 7 центров

• A. O. U. delle Marche — Torrette
• ASST Spedali Civili di Brescia — Brescia
• IRCCS Instituto G. Gaslini — Genova
• Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori (IRST) Dino Amadori — Meldola
• IRCCS San Gerardo Dei Tintori — Monza
• Bambino Gesu Children's Hospital — Roma
• AOU Città della salute e della scienza di Torino — Torino

Франция · 6 центров

• Institute of Hematology and Pediatric Oncology - Lyon — Lyon
• Hôpital Saint Louis — Paris
• Hospital Armand Trousseau Ap-Hp — Paris
• Hôpital Necker - Enfants Malade — Paris
• Centre Hospitalier Universitaire de Rennes — Rennes
• Institut Universitaire de Cancérologie de Toulouse - Oncopôle — Toulouse

Украина · 6 центров

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Великобритания · 6 центров

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Румыния · 5 центров

• Spitalul Clinic Colentina Site 1 — Bucharest
• Spitalul Clinic Colentina Site 2 — Bucharest
• Institutul Clinic Fundeni — Bucharest
• Institutul Clinic Fundeni — Bucharest
• … и ещё 1 центр

Turkey (Türkiye) · 5 центров

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Колумбия · 4 центра

• Fundacion Cardiovascular de Colombia-Instituto del Corazon Florida Blanca — Floridablanca
• Clinica IMBANACO S.A.S — Cali
• Clínica del Country — Chapinero
• Hospital Pablo Tobón Uribe — Medellín

Грузия · 4 центра

• LTD "Israeli-Georgian Medical Research Clinic Healthycore" — Tbilisi
• LEPL The First University Clinic of Tbilisi State Medical University — Tbilisi
• JSC K. Eristavi National Center of Experimental and Clinical Surgery — Tbilisi
• LTD Multiprofile Clinic Concilium Medulla — Tbilisi

Греция · 4 центра

• Hellenic Airforce 251 General Hospital — Athens
• University General Hospital of Heraklion — Heraklion
• The Olympion Private General Clinic — Pátrai
• AHEPA General Hospital of Thessaloniki — Thessaloniki

Индия · 4 центра

• Indira Gandhi Institute Of Medical Sciences — Patna
• Nirmal Hospital Private Limited — Surat
• Pacific Medical College and Hospital — Udaipur
• Yashoda Hospital — Hyderabad

Израиль · 4 центра

• Ruth Rappaport Children's Hospital, Rambam Health Corporation — Haifa
• Hadassah University Hospital-ein Kerem — Jerusalem
• Schneider Children's Medical Center of Israel — Petah Tikva
• The Chaim Sheba Medical Center — Ramat Gan

Португалия · 4 центра

• Unidade Local de Saúde da Região de Aveiro — Aveiro
• Unidade Local de Saude Coimbra - Paediatric Hospital — Coimbra
• Unidade Local de Saude Coimbra - Quinta dos Vales — Coimbra
• Unidade Local de Saude Santa Maria — Lisbon

Аргентина · 3 центра

• Hospital El Cruce — Buenos Aires
• Instituto de Investigaciones Clínicas Córdoba — Córdoba
• Santorio 9 de Julio — San Miguel de Tucumán

Австралия · 3 центра

• Perth Children's Hospital — Nedlands
• Icon Cancer Centre Southport — Southport
• Ballarat Oncology And Haematology Services — Wendouree

Венгрия · 3 центра

• CMC Deli Klinika — Budapest
• Semmelweis University — Budapest
• Teaching Hospital Markusovszky — Szombathely

Канада · 2 центра

• University of Alberta Hospital — Edmonton
• BC Children's Hospital — Vancouver

Чехия · 2 центра

• The University Hospital Brno — Brno
• Motol University Hospital — Prague

Германия · 2 центра

• Klinik und Poliklinik fur Kinder- und Jugendmedizin, Universitatsklinikum Carl Gustav Caru — Dresden
• Universitaetsklinikum Carl Gustav Carus Tu Dresden — Dresden

Швейцария · 2 центра

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Таиланд · 2 центра

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Бельгия · 1 центр

• Universitair Ziekenhuis Leuven — Leuven

Малайзия · 1 центр

• Hospital Pakar Kanak-Kanak UKM — Kuala Lumpur

Сербия · 1 центр

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Идентификаторы

NCT: NCT06056297 · X4P-001-110 · 2023-508482-32-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗