A Study of Mavorixafor in Participants With Congenital Neutropenia and Chronic Idiopathic Neutropenia Disorders

• Register: ClinicalTrials.gov
• Last refreshed on: 15 April 2024
• Main ID: NCT04154488
• Date of registration: 04/11/2019
• Prospective Registration: Yes
• Primary sponsor: X4 Pharmaceuticals
• Public title: A Study of Mavorixafor in Participants With Congenital Neutropenia and Chronic Idiopathic Neutropenia Disorders
• Scientific title: A Phase 1b/2, Open-Label, Multicenter Study of Mavorixafor in Patients With Congenital Neutropenia and Chronic Neutropenia Disorders
• Date of first enrolment: October 16, 2020
• Target sample size: 43
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT04154488
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

United States

Key inclusion & exclusion criteria

Key Inclusion Criteria:

For all participants (Parts 1 and 2):

- Sign the informed consent form (ICF) and be willing and able to comply with the
protocol.

- Weigh =15 kg

- Agree to use a highly effective form of contraception if sexually active.

- Participants may be eligible for the study whether they are on or off
granulocyte-colony stimulating factor (G-CSF) treatment.

- Note: Participants who are on G-CSF must be on a stable dose for =14 days prior
to the Baseline visit and should not have an ANC =10,000 cells/µL.

- Note: Participants who are not on G-CSF must be off for =14 days prior to the
Baseline visit and have an ANC =1000 cells/µL at the Screening visit.

- Note: Participants with Shwachman-Diamond syndrome, Cohensyndrome, and warts,
hypogammaglobulinemia, infections and myelokathexis syndrome are eligible. Other
types of chronic neutropenic disorders may also be eligible for enrollment upon
discussion and approval with Sponsor and Study Medical Monitor.

- Have been diagnosed with chronic neutropenia for =6 months prior to the Screening
visit that is not attributable to medications, active or recent (=3 months)
infections, or malignant cause.

Part 2 only:

- Participants enrolled in the study before implementation of Protocol Amendment 8.0
must have completed Part 1 and exhibited a positive response to treatment.

- Participant has a history of symptomatic chronic neutropenia confirmed by the
Investigator.

Key Exclusion Criteria (Parts 1 and 2):

- Known systemic hypersensitivity to the mavorixafor drug substance or its inactive
ingredients.

- Is pregnant, breastfeeding, or plans to become pregnant over the next 8 months.

- Known history of a positive serology or viral load for human immunodeficiency virus
(HIV) or a known history of acquired immune deficiency syndrome.

- Known active SARS-CoV-2 virus (COVID-19) infection or a positive test within the local
accepted clinical and governmental guidelines for a communicable window.

- At the Screening Visit, has a laboratory test result meeting one or more of the
following criteria:

- Positive hepatitis C virus (HCV) antibodies with confirmation by HCV-ribonucleic
acid polymerase chain reaction reflex testing.

- Positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody
(HBcAb).

- Note: If a participant tests negative for HBsAg but positive for HBcAb, the
participant would be considered eligible if the participant tests positive for
antibody to HBsAg reflex testing.

- At the Screening visit, has a laboratory test result meeting one or more of the
following criteria:

- Hemoglobin <9.0 grams/deciliter (g/dL)

- Platelets <30,000/µL

- Estimated glomerular filtration rate (eGFR) =60 mL/minute/1.73 meter (m)^2, as
estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
equation

- Serum aspartate transaminase >2.5 x upper limit of normal (ULN)

- Serum alanine transaminase >2.5 x ULN

- Total bilirubin >1.5 x ULN (unless due to Gilbert's syndrome, in which case total
bilirubin greater than or equal to (=) 3.0 x ULN and direct bilirubin >1.5 x ULN)

- =14 days before Day 1, received any of the following treatments:

- Systemic glucocorticoids (>5 mg prednisone equivalent per day).

- Medication prohibited based on cytochrome P450 (CYP), P-glycoprotein, OAT1, OCT2,
or MATE1 potential for interaction.

- Has an infection requiring use of systemic antibiotics =4 weeks before the Baseline
visit.

- Has a medical or personal condition that may potentially compromise the safety or
compliance of the participant, or may preclude the participant's successful completion
of the clinical study or that in the opinion of the Investigator or the Sponsor could
interfere with the objectives of the study.

- Has had major surgery =4 weeks before the Baseline visit.

- Inability to ingest mavorixafor capsules.

- Has an active malignancy or history of (=5 years prior to enrollment) in the study of
solid, metastatic, or hematologic malignancy. Exception: basal cell carcinoma in situ
of the skin that has been adequately treated.

- Diagnosed or has suspected congenital long QT syndrome. Any history of clinically
significant ventricular arrhythmias (such as ventricular tachycardia, ventricular
fibrillation, or torsades de pointes); any history of arrhythmia will be discussed
with the sponsor's medical monitor before participant's entry into the study.

- Prolonged corrected QT interval using Fridericia's formula at the Screening visit
electrocardiogram (ECG) (>450 milliseconds [ms])



Age minimum: 12 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Neutropenia

Intervention(s)

Drug: Mavorixafor

Primary Outcome(s)

Change From Baseline in ANC to Month 6 [Time Frame: Baseline, Month 6]

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) After a Single Dose of Mavorixafor [Time Frame: Baseline through Day 1 and 7 days follow-up]

Change From Baseline in Absolute Neutrophil Count (ANC) to 8 hours Post-dose On Day 1 [Time Frame: Baseline, 8 hours Post-dose On Day 1]

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) After Multiple Doses of Mavorixafor [Time Frame: Baseline through Month 6 and 30 days follow-up]

Secondary Outcome(s)

AUC of AMC (AUCAMC) [Time Frame: Baseline up to Month 6]

Change from Baseline in Absolute Lymphocyte Count (ALC) [Time Frame: Baseline, Month 6]

Change from Baseline in Absolute Monocyte (AMC) [Time Frame: Baseline, Month 6]

Serum Concentrations of Mavorixafor [Time Frame: 0 (pre-dose) up to Month 6]

AUC of ANC (AUCANC) [Time Frame: Baseline up to Month 6]

AUC of WBC (AUCWBC) [Time Frame: Baseline up to Month 6]

Serum Concentration of Mavorixafor in Relation to ANC and Area Under the Curve (AUC) for ANC (AUCANC) [Time Frame: 0 (pre-dose), 60 minutes and 2, 3, 4, 6, and 8 hours post-dose on Day 1]

AUC of ALC (AUCALC) [Time Frame: Baseline up to Month 6]

Change from Baseline in Total White Blood Cells (WBC) [Time Frame: Baseline, Month 6]

Secondary ID(s)

X4P-001-104

Source(s) of Monetary Support

Please refer to primary and secondary sponsors