Resumen

El propósito de este estudio es demostrar la eficacia y evaluar la seguridad y tolerabilidad de mavorixafor en participantes con trastornos neutropénicos crónicos primarios congénitos o adquiridos, autoinmunes e idiopáticos, que presentan infecciones recurrentes y/o graves, evaluado mediante la demostración de su beneficio clínico y el aumento de los niveles de neutrófilos circulantes.

Descripción detallada

Todos los participantes continuarán con su tratamiento de base previo al estudio, definido como el régimen de tratamiento actual del participante. Las opciones incluyen, entre otras: factor estimulante de colonias de granulocitos (G-CSF), terapia de reemplazo con inmunoglobulinas, antibióticos profilácticos o «espera vigilante».

Elegibilidad

Edad mínima: 12 YearsSexo: ALL

Criterios de inclusión

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.

Criterios de exclusión

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.

Estudio de fase 3, aleatorizado, doble ciego, controlado con placebo y multicéntrico de mavorixafor en participantes con trastornos neutropénicos crónicos primarios congénitos y adquiridos, autoinmunes e idiopáticos, que presentan infecciones recurrentes y/o graves

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Mavorixafor

Placebo

Ubicaciones

Hospital El Cruce

Instituto de Investigaciones Clínicas Córdoba

Santorio 9 de Julio

Patrocinadores

Contactos

Patient Affairs and Advocacy