A study to investigate the efficacy, safety, and tolerability of Mavorixafor in participants with congenital and acquired primary autoimmune diseases and idiopathic chronic neutropenic disorders who suffer from recurrent and/or severe infections.
Zusammenfassung der Studie
You are suffering from a condition of the immune system known as chronic neutropenia. It can be caused by both genetic factors you were born with and factors that have developed over time; it is primary (i.e., not caused by another condition known to you) and affects the body's production of white blood cells (congenital and acquired primary autoimmune disease and idiopathic chronic neutropenic disorder). You are currently receiving treatment for your chronic neutropenia (background treatment), but despite adhering to your current treatment plan, you are experiencing frequent and/or severe infections. Mavorixafor is being developed by the sponsor as a potential treatment for patients with chronic neutropenia. The purpose of the study is to demonstrate efficacy and assess the safety and tolerability of Mavorixafor (study medication) in conjunction with your background therapy. If you decide to participate, you will be asked to undergo physical examinations regarding your past and current health, provide blood samples for laboratory analyses, and complete a series of questionnaires about the medications you are taking, your overall well-being, and any wounds throughout the study. Participation in the study lasts approximately 63 weeks. The dose and schedule of your background therapy will remain the same throughout the study unless it is necessary to change the dose and/or schedule for safety reasons. If you withdraw from the study, you will need to attend an appointment at the end of treatment. There are 2 possible treatment groups (study medication or placebo) to which you may be randomly assigned with a one-to-one probability.
(BASEC)
Untersuchte Intervention
Mavorixafor is a medication that has been shown in other studies with patients to increase the number of certain white blood cells in the blood. White blood cells include cells that fight infections, particularly the cells known as neutrophils. An increase in the number of neutrophils in your blood is expected to help your body fight infections. An increase in the number of neutrophils in your blood may not cause any symptoms and can only be detected through blood tests. The study medication is Mavorixafor, an investigational product that has not yet been approved by the regulatory authorities in your country for the indication of this study. This study medication has received FDA approval in the USA for WHIM syndrome.
(BASEC)
Untersuchte Krankheit(en)
Congenital and acquired primary autoimmune and idiopathic chronic neutropenic disorders
(BASEC)
1. Participants must be at least 12 years old at the time of signing the informed consent form. Informed consent must comply with local regulations and guidelines. 2. Diagnosis of congenital or acquired primary autoimmune and idiopathic chronic neutropenia at least 6 months prior to the screening visit, which is NOT due to medications, active or recent infections, or malignancies. - Congenital neutropenia, including but not limited to the following classifications: a. Isolated with a permanent (non-cyclic) presentation, e.g., ELANE, CSF3R, CXCR2, WAS b. Associated with extra-hematological manifestations, e.g., Barth syndrome, Cohen syndrome, G6PC3, Kostmann disease c. Associated with metabolic disorders, e.g., glycogen storage disease 1b (GSD1b) d. Shwachman-Diamond syndrome - Acquired primary neutropenia a. Chronic idiopathic neutropenia b. Primary autoimmune neutropenia. Other CNS disorders that may qualify for inclusion in the study can be clarified and approved in consultation with the medical study management and the sponsor. Discussion with the medical monitor of the study and the sponsor is required for approval. 10. The participant, a parent, and/or the appropriate legal representative is able to provide the signed ICF and/or consent as per Appendix 1, Section 10.1.3, which includes compliance with the requirements and restrictions outlined in the ICF and this protocol. (BASEC)
Ausschlusskriterien
1. The participant is incapacitated and cannot meet the protocol-specific requirements. 2. Diagnosis of secondary neutropenia, including those due to: a. Hypersplenism b. Infection c. Malignancy d. Autoimmune disease, e.g., systemic lupus erythematosus, rheumatoid arthritis, irritable bowel disease, graft-versus-host disease, thyroid disease e. Nutritional deficiency, e.g., vitamin B12, folate, copper, caloric malnutrition f. Drug-induced causes, e.g., chemotherapy, clozapine, antiretroviral medications, antibiotics, monoclonal antibodies. 3. One of the following diagnoses: - Aplastic anemia - WHIM syndrome - Certain CNS disorders, including but not limited to the following classifications, are excluded: a. Isolated with cyclic occurrence, e.g., ELANE b. Associated with immune dysregulation, e.g., CVID, ALPS, familial hemophagocytic lymphohistiocytosis, Chédiak-Higashi syndrome, GATA2 deficiency syndrome c. Associated with bone marrow failure, e.g., 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 still be eligible for inclusion. (BASEC)
Studienstandort
Bern
(BASEC)
Sponsor
Sponsor: X4 Pharmaceuticals Inc. 61 North Beacon Street, 4th Floor, Boston, MA 02134 USA Sponsor's Representative in Switzerland: FGK Representative Service AG Mitteldorf 20, 5637 Beinwil (Freiamt), Schweiz
(BASEC)
Kontakt für weitere Auskünfte zur Studie
Kontaktperson Schweiz
Christopher Arbet-Engels
+18575298300
christophe.arbet-engels@clutterx4pharma.comX4 Pharmaceuticals Inc. 61 North Beacon Street, 4th Floor, Boston, MA 02134 USA
(BASEC)
Allgemeine Auskünfte
X4 Pharmaceuticals
857-529-5779
christophe.arbet-engels@clutterx4pharma.com(ICTRP)
Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)
Ethikkommission Bern
(BASEC)
Datum der Bewilligung durch die Ethikkommission
10.01.2025
(BASEC)
ICTRP Studien-ID
NCT06056297 (ICTRP)
Offizieller Titel (Genehmigt von der Ethikkommission)
Eine randomisierte, doppelblinde, placebokontrollierte, multizentrische Phase-III-Studie zu Mavorixafor bei Teilnehmern mit angeborenen und erworbenen primären Autoimmunerkrankungen und idiopathischen chronischen Neutropenie-Erkrankungen, die unter wiederkehrenden und/oder schweren Infektionen leiden (BASEC)
Wissenschaftlicher Titel
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 (ICTRP)
Öffentlicher Titel
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 (ICTRP)
Untersuchte Krankheit(en)
Neutropenia (ICTRP)
Untersuchte Intervention
Drug: MavorixaforDrug: Placebo (ICTRP)
Studientyp
Interventional (ICTRP)
Studiendesign
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor). (ICTRP)
Ein-/Ausschlusskriterien
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/L 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/L 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, Chdiak-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. (ICTRP)
nicht verfügbar
Primäre und sekundäre Endpunkte
Annualized Infection Rate Based on Infections Adjudicated by Blinded Infection Adjudication Committee (BIAC) During the Treatment Period;Number of Participants Meeting the Definition of a Positive Absolute Neutrophil Count (ANC) Response (ICTRP)
Infection Severity Based on Common Terminology Criteria for Adverse Events (CTCAE) Adjudicated by a BIAC During the Treatment Period;Infection Duration Based on Duration of Infections Adjudicated by a BIAC During the Treatment Period in Those Participants who Developed Infections;Antibiotic Use Due to Infection, Characterized by the Frequency of Antibiotic Use During the Treatment Period;Oral Ulcers, as Assessed by Presence or Absence of Ulcers During the Treatment Period;Change From Baseline in Patient Reported Outcomes Measurement Information System Short Form (PROMIS SF) Fatigue Questionnaire Total Score (ICTRP)
Registrierungsdatum
nicht verfügbar
Einschluss des ersten Teilnehmers
nicht verfügbar
Sekundäre Sponsoren
nicht verfügbar
Weitere Kontakte
Chief Medical OfficerPatient Affairs and Advocacy, clinicaltrialinfo@x4pharma.com, 857-529-5779, X4 Pharmaceuticals (ICTRP)
Sekundäre IDs
2023-508482-32-00, X4P-001-110 (ICTRP)
Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar
Weitere Informationen zur Studie
https://clinicaltrials.gov/ct2/show/NCT06056297 (ICTRP)
Ergebnisse der Studie
Zusammenfassung der Ergebnisse
nicht verfügbar
Link zu den Ergebnissen im Primärregister
nicht verfügbar